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Objective: To examine the associations between microvascular disease (MVD) and risk of stroke, dementia, and their major subtypes among individuals with type 2 diabetes mellitus (T2DM)., Methods: We included 26,173 participants with T2DM from the UK Biobank who had no known stroke or dementia at baseline. MVD burden was reflected by the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidential intervals (CIs) of stroke and dementia associated with overall MVD burden and individual MVD., Results: During a median follow-up of 11.5 years, 1103 incident stroke (964 ischemic and 269 hemorrhagic stroke) and 813 incident dementia (312 Alzheimer's disease and 304 vascular dementia) cases were identified. The risk of stroke, dementia, and their major subtypes all increased with an increasing number of MVD (all P-trend <0.001). The adjusted HRs (95 % CIs) comparing three with no MVD were 5.03 (3.16, 8.02) for all stroke, 4.57 (2.75, 7.59) for ischemic stroke, and 6.60 (2.65, 16.43) for hemorrhagic stroke. The corresponding estimates were 4.28 (2.33, 7.86) for all-cause dementia, 6.96 (3.02, 16.01) for Alzheimer's disease, and 3.81 (1.40, 10.42) for vascular dementia. Among the three MVD, chronic kidney disease showed the strongest associations with both stroke subtypes, while peripheral neuropathy was most strongly associated with both dementia subtypes., Conclusions: Risk of stroke, dementia, and their major subtypes increased with an increasing number of MVD. The associations of individual MVD with stroke and dementia varied substantially by types of MVD., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia., Methods: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis., Results: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis., Limitations: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed., Conclusions: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia., Competing Interests: Declaration of competing interest The authors declare there are no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Several studies have demonstrated a higher frequency of seizures and epilepsy in Alzheimer's disease and other forms of dementia as compared with healthy elderly individuals. However, incidence and prevalence of epilepsy in the general population of dementia are unknown since most previous studies were performed in secondary-tertiary referral centres. In addition, all prior studies but one provided "period" rather than "point" prevalence estimates., Methods: We assessed point prevalence estimate of epileptic manifestations requiring antiepileptic medication in patients Alzheimer's disease, vascular dementia, and fronto-temporal dementia from a secondary clinical setting., Results: Point prevalence estimates were 6.4% (95% CI: 1.5 to 11.3) in Alzheimer's disease, 8.9% (95% CI: 1.4 to 16.4), in vascular dementia, and 6% (95% CI: 1.3 to 10.7) in fronto-temporal dementia, rates that were greater than those observed in the healthy elderly population. Regardless of the etiology of dementia, epilepsy was characterized by unprovoked seizures that lacked distinguishing clinical features., Significance: These findings support epilepsy as part of the spectrum of dementia. The similar point prevalence of definite epilepsy requiring AED treatment in Alzheimer's disease and non Alzheimer dementias raised the possibility of similar underlying mechanism of epileptogenesis. Although this was not a population-based study, accurate point prevalence data from clinic setting would be important to better define the burden of epilepsy in dementia and the demands on health services to manage the condition., (© 2024 International League Against Epilepsy.)

Introduction: Neurological conditions such as Alzheimer's disease and stroke represent a substantial health burden to the world's ageing population. Cerebrovascular dysfunction is a key contributor to these conditions, affecting an individual's risk profile, age of onset, and severity of neurological disease. Recent data shows that early-life events, such as maternal health during pregnancy, birth weight and exposure to environmental toxins can 'prime' the vascular system for later changes. With age, blood vessels can become less flexible and more prone to damage. This can lead to reduced blood flow to the brain, which is associated with cognitive decline and an increased risk of stroke and other cerebrovascular diseases. These in turn increase the risk of vascular dementia and Alzheimer's disease., Objectives: We aim to explore how early life factors influence cerebrovascular health, ageing and disease., Methods: We have reviewed recently published literature from epidemiological studies, clinical cases and basic research which explore mechanisms that contribute to cerebrovascular and blood-brain barrier dysfunction, with a particularly focus on those that assess contribution of early-life events or vascular priming to subsequent injury., Results: Perinatal events have been linked to acute cerebrovascular dysfunction and long-term structural reorganisation. Systemic disease throughout the lifetime that produce inflammatory or oxidative stress may further sensitise the cerebrovasculature to disease and contribute to neurodegeneration., Conclusions: By identifying these early-life determinants and understanding their mechanisms, scientists aim to develop strategies for preventing or mitigating cerebrovascular ageing-related issues., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice., Competing Interests: Disclosures Drs Clancy, Maniega, Quinn, Jochems, and Valdés Hernández, A.K. Kancheva, and J.M. Wardlaw report academic research grants as detailed in the Sources of Funding. J.M. Wardlaw chairs the European Stroke Organisation Guideline on small vessel disease. Dr Quinn reports grants from Bristol Myers Squibb and Shionogi and advises on ESO Guidelines.

Background: Patients with intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) are at increased risk of developing epilepsy and cognitive disorders such as Alzheimer's disease (AD), mild cognitive impairment (MCI), and vascular dementia. In a retrospective cohort observation study of patients hospitalized for ICH with CAA versus ICH without CAA, we evaluated the prevalence of neurological comorbidities at admission and the risk of new diagnosis of epilepsy, relevant cognitive disorders, and mortality at 1 year., Methods: In the TriNetX health research network, adult patients aged ≥ 55 years hospitalized with a diagnosis of ICH were stratified based on presence or absence of concomitant CAA diagnosis. Demographics and medical comorbidities were compared by using χ 2 test and Student's t-test. After 1:1 propensity score matching, 1-year survival was assessed with Kaplan-Meier curves. The 1-year risk of new diagnosis of epilepsy, AD, MCI, vascular dementia, and dementia unspecified was assessed with Cox proportional hazards estimate., Results: The study included a total of 1757 patients with ICH and CAA and 53,364 patients with ICH without CAA. Patients with CAA were older compared with those without CAA (74.1 ± 7.5 vs. 69.8 ± 8.8 years, p ≤ 0.001). Compared with ICH without CAA, patients with ICH and CAA had higher baseline prevalence of cerebral infarction (30% vs. 20%), nontraumatic ICH (36% vs. 7%), nontraumatic subarachnoid hemorrhage (14% vs. 5%), epilepsy (11% vs. 6%), and AD (5% vs. 2%) with significance at p < 0.001. After propensity score matching, a total of 1746 patients were included in both cohorts. In the matched cohorts, compared with patients with ICH without CAA, patients with ICH and CAA had lower 1-year all-cause mortality (479 [27%] vs. 563 [32%]; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.71-0.90) and higher risk of new diagnosis of epilepsy (280 [18%] vs. 167 [11%]; HR 1.70; 95% CI 1.40-2.06), AD (101 [6%] vs. 38 [2%]; HR 2.62; 95% CI 1.80-3.80), MCI (85 [5%] vs. 35 [2%]; HR 2.39; 95% CI 1.61-3.54), vascular dementia (117 [7%] vs. 60 [4%]; HR 1.92; 95% CI 1.41-2.62), and dementia unspecified (245 [16%] vs. 150 [9%]; HR 1.70; 95% CI 1.39-2.08)., Conclusions: Among patients admitted for ICH, patients with CAA have lower mortality but have 2-3 times more risk of diagnosis of epilepsy and dementia at 1 year, compared with those without CAA., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Aims: The aim of the study was to disentangle the contributions of alcohol and alcohol-related liver disease (ALD) towards dementia by independently measuring the association between alcohol use disorder (AUD) alone and ALD with dementia., Design: This was a nation-wide cohort study., Setting: The study was conducted in Sweden from 1987 to 2020., Participants: DELIVER (DEcoding the epidemiology of LIVER disease in Sweden) cohort, containing administrative codes on patients with chronic liver disease from the National Patient Register and other registers between 1987 and 2020., Measurements: International Classification of Disease 9th (ICD-9) and 10th (ICD-10) version codes were used to define the presence of AUD, ALD and dementia. The associations of AUD alone and ALD with incident dementia were estimated using Cox regression models adjusting for potential confounders. Cumulative incidences were also calculated accounting for competing risks of death., Findings: A total of 128 884 individuals with AUD alone, 17 754 with ALD and 2 479 049 controls were identified. During a median follow-up of 8.9 years, 13 395 (10.4%), 2187 (12.3%) and 138 925 (5.6%) dementia cases were identified in these groups, respectively. Dementia rates were increased in AUD alone [adjusted hazard ratio (aHR) = 4.6, 95% confidence interval (CI) = 4.5-4.6] and in ALD (aHR = 8.6, 95% CI = 8.3-9.0) compared with controls. AUD alone was also associated with increased rates of vascular dementia (aHR = 2.3, 95% CI = 2.2-2.5) and Alzheimer's disease (aHR = 1.4, 95% CI = 1.3-1.4), while ALD was only associated with vascular dementia (aHR = 2.7, 95% CI = 2.3-3.2). The median age at dementia diagnosis was 67 years [interquartile range (IQR) = 56-76] in AUD alone and 63 years (IQR = 56-71) in ALD compared with 85 years (IQR = 79-89) in controls., Conclusion: In Sweden, patients with alcohol use disorder (AUD) appear to have increased rates of dementia and diagnosis at a younger age, compared with patients without AUD. Concurrent alcohol-related liver disease appears to increase the diagnosis rate and lower the median age further., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Purpose: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort., Design: National matched cohort study., Participants: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia., Methods: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for sociodemographic factors and comorbidities., Main Outcome Measures: Alzheimer's disease, VaD, and all-cause dementia identified from nationwide inpatient and outpatient diagnoses through 2018., Results: In 16 million person-years of follow-up, 32 339 persons (10%) with glaucoma and 226 896 controls (7%) were diagnosed with dementia. Persons with glaucoma had increased risks for AD (adjusted HR, 1.39; 95% confidence interval [CI], 1.35-1.43), VaD (1.66; 1.61-1.72), and all-cause dementia (1.57; 1.54-1.59). Among glaucoma subtypes, both primary open-angle and normal-tension glaucoma were associated with increased risk for AD (adjusted HR, 1.31; 95% CI, 1.27-1.36; and 1.28; 1.20-1.36, respectively) and VaD (1.61; 1.54-1.68; and 1.39; 1.28-1.50, respectively), whereas primary angle-closure glaucoma was associated with VaD (1.26; 1.02-1.56) but not AD (0.98; 0.82-1.18). These findings were similar in men and women. All risks were highest in persons diagnosed with glaucoma at ages ≥ 70 years and were not elevated for ages < 60 years., Conclusions: In this large national cohort, persons with glaucoma had increased risks for AD, VaD, and all-cause dementia, particularly those diagnosed with glaucoma at older ages. Persons with glaucoma may need increased monitoring for dementia to facilitate earlier detection and treatment., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background:  Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes., Methods:  Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group)., Results:  The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching., Conclusion:  In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Aim: Atrial fibrillation (AF) is associated with increased risk of dementia. Whether direct oral anticoagulation (DOAC) reduce this risk compared to vitamin-K antagonist (VKA) is unclear. The aim of this study was to assess the risk of new all-cause dementia and vascular dementia in AF patients, treated with either DOAC or VKAs., Methods: Anonymized electronic medical records from the TriNetX federated research network were used. AF patients treated with DOACs within 1 month of AF diagnosis, were 1:1 propensity score-matched with those treated with a VKA. The analysis included patients who completed 5 and 10 years of follow-up and were assessed for all-cause dementia and vascular dementia. Cox proportional hazard models were used to hazard ratios (HR), respectively with 95% confidence intervals (CIs)., Results: Among patients who completed 5 years of follow-up, after propensity score matching the final cohort consisted of 215,404 well-matched AF patients. All-cause dementia was diagnosed in 4,153 (3.9%) patients among those treated with DOACs and 4,150 (3.9%) among the VKA-treated patients (HR: 1.01, 95%CI: 0.96-1.05). Among patients 65-74 years old who were followed, DOAC treatment was associated with lower risk of dementia compared to VKAs (HR: 0.72; 95%CI: 0.59-0.86). Among patients who completed 10 years of follow-up, after propensity score matching the final cohort consisted of 19,208 well-matched AF patients. All-cause dementia was diagnosed in 314 (3.3%) patients among those treated with DOACs and 451 (4.7%) among the VKA-treated patients. DOAC treatment was associated with significantly lower risk of all-cause dementia during a follow-up period of 10 years compared to VKA treatment (HR: 0.72, 95%CI: 0.62-0.83), which remained consistent in patiens ≥65 years old., Conclusion: This propensity-score matched analysis showed that among AF patients, treatment with a DOACs for a period of 10 years was associated with lower risk of all-cause dementia and vascular dementia compared to VKA treatment, an effect which was not apparent in those treated for shorter duration. This finding requires confirmation in ongoing randomised controlled trials., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

White matter lesions induced by chronic cerebral hypoperfusion can cause vascular dementia; however, no appropriate treatments are currently available for these diseases. In this study, we investigated lipid peroxidation, which has recently been pointed out to be associated with cerebrovascular disease and vascular dementia, as a therapeutic target for chronic cerebral hypoperfusion. We used ethoxyquin, a lipid-soluble antioxidant, in a neuronal cell line and mouse model of the disease. The cytoprotective effect of ethoxyquin on glutamate-stimulated HT-22 cells, a mouse hippocampal cell line, was comparable to that of a ferroptosis inhibitor. In addition, the administration of ethoxyquin to bilateral common carotid artery stenosis model mice suppressed white matter lesions, blood-brain barrier disruption, and glial cell activation. Taken together, we propose that the inhibition of lipid peroxidation may be a useful therapeutic approach for chronic cerebrovascular disease and the resulting white matter lesions.

Objectives: The aim of this study was to investigate whether cataract disease is associated with the risk of developing dementia or cognitive impairment., Methods: A systematic search of the literature in PubMed, the Extracts Database (Embase), the Cochrane Library and the Web of Science databases was performed from the inception data of each database until 1 September 2022. Sensitivity analyses were performed to assess the robustness and reliability of the overall findings. All extracted data were statistically analyzed using Stata software v.16.0. Publication bias was assessed using funnel plots and the Egger test., Results: There were 11 publications included in this study, which consisted of 489,211participants, spanning 10 countries from 2012 to 2022. Aggregation suggested that cataracts were associated with cognitive impairment (odds ratio [OR] = 1.32; 95% CI: 1.21-1.43; I 2 = 45.4.%; p  = 0.000). The presence of cataracts is significantly associated with an increased risk of developing all-cause dementia (relative risk [RR] = 1.17; 95% CI: 1.08-1.26; I 2 = 0.0%; p  = 0.000). In subgroup analyses, having cataracts may increase the risk of Alzheimer's disease (hazard ratio [HR] = 1.28; 95% CI: 1.13-1.45; I 2 = 0.0%; p  = 0.000) and vascular dementia (HR = 1.35; 95% CI = 1.06-1.73; I2 = 0.0%, p  = 0.015). The data from the Egger's test showed no significant evidence of publication bias., Conclusions: Cataracts are associated with the risk of cognitive impairment and dementia, including Alzheimer's disease, and vascular dementia.

Background: Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia., Methods: To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders: plethysmography and electroencephalographic/electromyographic recordings were used to assess sleep-wake state, breathing parameters, and sleep-disordered breathing; immunocytochemistry was used to assess vascular and neural health; the forced alteration Y maze and Barnes maze were used to assess short- and long-term memories, respectively; and an anesthetized preparation was used to assess baroreflex sensitivity., Results: Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories., Conclusions: Therefore, we postulate that hypertension induces SA through vascular damage in the respiratory column, culminating in neuronal loss in the inspiratory oscillator. This induction of SA, which, in turn, will independently exacerbate hypertension and neural inflammation, increases the rate of vascular dementia., Competing Interests: Disclosures None.

Introduction: Dementia after stroke is common and is a great concern for patients and their caregivers. The objective was to investigate if intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) was associated with lower risk of dementia after stroke., Patients and Methods: When IVT was introduced in Denmark, not all eligible patients were treated due to restricted access. We conducted a nationwide register-based cohort study of all patients with AIS in Denmark from 2004 to 2011. IVT-treated patients were propensity score-matched with comparable non-treated patients. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for all-cause and vascular dementia 2, 5, and 10 years after stroke., Results: Of the 5919 patients eligible for the study, 2305 IVT-treated patients were propensity score-matched with 2305 non-treated patients. Mean (SD) age was 66.6 (13.3) and 61.2% were male. Rate of all-cause dementia was lower for the IVT-treated 2 years (8.4/1000 person years (PY) vs 13.6/1000 PY, HR 0.63 (0.40-0.99)) and 5 years after stroke (7.3/1000 PY vs 11.4/1000 PY, HR 0.65 (0.46-0.91)). 10 years after stroke, the rates of all-cause dementia remained in favor of IVT (8.0/1000 PY vs 9.8/1000 PY, HR 0.83 (0.64-1.07)). IVT-treated had lower rates of vascular dementia 2 years (2.4/1000 PY vs 7.4/1000 PY, HR 0.33 (0.15-0.71)), 5 years (2.3/1000 PY vs 6.2/1000 PY, HR 0.38 (0.23-0.65)), and 10 years after stroke (3.0/1000 PY vs 5.4/1000 PY, HR 0.56 (0.38-0.81))., Conclusion: IVT treatment was associated with lower long-term risk of both vascular and all-cause dementia after AIS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background The majority of patients survive the acute phase of myocardial infarction (MI) but have an increased risk of recurrent cardiovascular disease (CVD) events. To be regularly physically active or change activity level is associated with a lower risk of all-cause mortality. The objective was to explore to what extent physical activity (PA) levels or change in PA levels during the first year post-MI was associated with any recurrent nonfatal CVD events and specific CVD events (eg, MI, ischemic stroke, and vascular dementia). Methods and Results This cohort study among MI survivors was based on Swedish national registries between 2005 and 2020. PA levels were self-rated at 2 and 12 months post-MI, and patients were classified into remaining physically inactive, increasing, decreasing, or remaining active. A total of 6534 nonfatal CVD events occurred during 6 years of follow-up among the 47 153 included patients. In fully adjusted analyses, the risk of any nonfatal CVD event was lower ( P <0.05) among patients remaining active (37%), increasing (22%), or decreasing (18%) PA level compared with remaining inactive. Compared with remaining inactive, the risk of recurring MI and stroke was lower ( P >0.05) among remaining active (41% versus 52%, respectively), increasing (20% versus 35%, respectively), or decreasing PA level (24% versus 34%, respectively). For vascular dementia, patients remaining physically active had an 80% lower risk compared with remaining inactive ( P <0.05). Conclusions Remaining physically active or change in PA levels during the first year post-MI was associated with a lower risk of recurrent nonfatal CVD events. This emphasizes the importance of supporting patients to continue to be or become physically active.

Background: The effect of amyloid-β (Aβ) on cognitive impairment in patients with small subcortical infarction remains controversial, although a growing body of evidence shows a substantial overlap between Alzheimer's disease (AD) and subcortical ischemic vascular dementia, another form of cerebral small vessel disease (cSVD). Therefore, we investigated the relationships between Aβ positivity and the development of post-stroke cognitive impairment (PSCI) in patients with small subcortical infarction., Methods: We prospectively recruited 37 patients aged ≥ 50 years, with first-ever small subcortical infarction, who underwent amyloid positron emission tomography, 3 months after stroke at Korea University Guro Hospital. We also enrolled CU participants matched for age and sex with stroke patients for comparison of Aβ positivity. Patients were followed up at 3 and 12 months after the stroke to assess cognitive decline. Logistic and linear mixed-effect regression analyses were performed to identify the effect of Aβ positivity on PSCI development and long-term cognitive trajectories., Results: At 3 months after stroke, 12/37 (32.4%) patients developed PSCI, and 11/37 (29.7%) patients had Aβ deposition. Aβ positivity (odds ratio [OR] = 72.2, p = 0.024) was predictive of PSCI development regardless of cSVD burden. Aβ positivity (β = 0.846, p = 0.014) was also associated with poor cognitive trajectory, assessed by the Clinical Dementia Rating-Sum of Box, for 1 year after stroke., Conclusions: Our findings highlight that Aβ positivity is an important predictor for PSCI development and cognitive decline over 1 year. Furthermore, our results provide evidence that anti-AD medications may be a strategy for preventing cognitive decline in patients with small subcortical infarctions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Although hypertension is a critical risk factor for dementia, the association between primary aldosteronism (PA) and dementia has been scarcely reported. We aimed to investigate whether the risk of dementia in patients with PA was elevated compared with patients with essential hypertension (EH)., Methods: From the National Health Insurance Claim database in Korea (2003-2017), 3,687 patients with PA (adrenalectomy [ADX], n = 1,339, mineralocorticoid receptor antagonist [MRA] n = 2,348) with no prior dementia were age- and sex-matched at a 1:4 ratio to patients with EH (n = 14,741). The primary outcomes were all-cause dementia events, including Alzheimer's disease, vascular dementia, or other dementia combined with a prescription of one or more medications for dementia (donepezil, galantamine, memantine, or rivastigmine). Multivariable Cox regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals for the outcome incidence rates between patients with PA and their EH matches., Results: During a median follow-up of 5.2 years, there were 156 cases of all-cause dementia (4.2%), 140 cases of Alzheimer's disease (3.8%), and 65 cases of vascular dementia (1.8%). Compared with EH, the risk of all-cause dementia was increased in treated PA (unadjusted hazard ratio [HR] 1.26; p < 0.011). Among PA, MRA group had higher risks of all-cause dementia, especially vascular dementia, adjusted for age, sex, income, comorbidities, and concurrent medication (adjusted HR 1.31; p = 0.027 and adjusted HR 1.62; p = 0.020, respectively) compared to EH. ADX group seemed to have a lower dementia risk than the EH group, but there was no statistical significance after full adjustment. This trend became more prominent when the dementia risks were evaluated from the time of hypertension diagnosis rather than treatment initiation for PA., Conclusion: The findings of this cohort study suggest that PA, especially the MRA group, is associated with an increased risk of dementia. Monitoring cognitive function in PA patients even after treatment initiation might be warranted to prevent dementia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD., Methods: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE., Results: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms., Conclusion: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Cataract has been shown to be associated with an increased risk of cognitive impairment. However, the results of previous studies have been inconsistent. This systematic review and meta-analysis aimed to investigate the association between cataract and the incidence of cognitive impairment in older adults., Methods: A comprehensive search of electronic databases from inception to January 2023 was performed to identify relevant studies. Data were extracted from eligible studies and a meta-analysis was performed to calculate the pooled hazard ratio (HR) and 95% confidence interval (CI)., Results: We included 13 studies with 25 study arms involving a total of 798,694 participants. Compared with participants without cataract, those with cataract had a higher risk of developing all-cause dementia (pooled HR: 1.22; 95 % CI: 1.08-1.38; I 2 =86 %; 9 studies), Alzheimer's disease dementia (pooled HR: 1.18; 95 % CI: 1.07-1.30; I 2 =0 %; 9 studies), vascular dementia (pooled HR: 1.21; 95 % CI: 1.02-1.43; I 2 =77 %;3 studies) and mild cognitive impairment (pooled HR: 1.30; 95% CI: 1.13-1.50; I 2 =0%;2 studies). There was no significant association between cataract and mixed dementia (pooled HR: 1.03; 95 % CI: 0.52-2.04; I 2 =78 %;2 studies). We assessed the risk of bias of the included studies using the Newcastle-Ottawa Scale and found that most of them had a low or moderate risk of bias. The number of studies in each meta-analysis ranged from two to nine, with more studies available for all-cause dementia and Alzheimer's disease dementia than for vascular dementia and mixed dementia., Conclusions: The findings suggest that cataract may be associated with cognitive impairment in older adults. However, the causal relationship between cataract and cognition remains unclear and requires further investigation., Competing Interests: Declaration of Competing Interest The authors have no conflicts., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dementia of vascular origin is a distinct variety with a heterogeneous neuropsychological profile. Very few studies have compared the behavioral dysfunction in the large vessel and small vessel vascular dementia (VaD) and studied the association between executive dysfunction and behavioral dysfunction documented in these patients, between the white matter load in small vessel disease (SVD) and the behavioral dysfunction. 76 patients having a modified Hachinski Ischemic Scale score of ≥ 4 were recruited and categorized into a small vessel and large vessel VaD. The Neuropsychiatric Inventory (NPI) score ≥ 4 per domain for defining clinically relevant symptoms and the Clinical Dementia Rating Scale (CDR) for evaluating the severity of dementia were used. Behavioral and Psychological Symptoms of Dementia (BPSD) were present in 66.67% of patients with SVD and 53.57% of those having large vessel disease. Apathy, euphoria, and disinhibition were more common in SVD, while appetite alterations were more common in large vessel disease. Behavioral dysfunction was also associated with executive dysfunction in both the VaD subtypes and with white matter loads in SVD. We conclude that different VaD subtypes have different behavioral profiles. This might help in understanding the underlying pathophysiology, diagnosis and thus better management of this disorder.

Objective: Cerebral small vessel disease (SVD) is considered the most important vascular contributor to cognitive decline and dementia, although a causal relation between its MRI markers and dementia still needs to be established. The authors investigated the relation between baseline SVD severity as well as SVD progression on MRI markers and incident dementia, by subtype, in individuals with sporadic SVD over a follow-up period of 14 years., Methods: The study included 503 participants with sporadic SVD, and without dementia, from the prospective Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, with screening for baseline inclusion conducted in 2006. Follow-ups in 2011, 2015, and 2020 included cognitive assessments and MRI scans. Dementia was diagnosed according to DSM-5 criteria and stratified into Alzheimer's dementia and vascular dementia., Results: Dementia as an endpoint was available for 498 participants (99.0%) and occurred in 108 participants (21.5%) (Alzheimer's dementia, N=38; vascular dementia, N=34; mixed-etiology Alzheimer's dementia/vascular dementia, N=26), with a median follow-up time of 13.2 years (interquartile range, 8.8-13.8). Higher baseline white matter hyperintensity (WMH) volume (hazard ratio=1.31 per 1-SD increase, 95% CI=1.02-1.67), presence of diffusion-weighted-imaging-positive lesions (hazard ratio=2.03, 95% CI=1.01-4.04), and higher peak width of skeletonized mean diffusivity (hazard ratio=1.24 per 1-SD increase, 95% CI=1.02-1.51) were independently associated with all-cause dementia and vascular dementia. WMH progression predicted incident all-cause dementia (hazard ratio=1.76 per 1-SD increase, 95% CI=1.18-2.63)., Conclusions: Both baseline SVD severity and SVD progression were independently associated with an increase in risk of all-cause dementia over a follow-up of 14 years. The results suggest that SVD progression precedes dementia and may causally contribute to its development. Slowing SVD progression may delay dementia onset., Competing Interests: Dr. Claassen is local principal investigator at Radboudumc for the EVOKE study sponsored by Novo Nordisk. Dr. Duering has served as a consultant for Roche, as a speaker for Bayer and Sanofi, and as an adjudication board member for Hovid Berhad. The other authors report no financial relationships with commercial interests.

Background: Atrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the association between AD or vascular dementia and adverse outcomes in AF patients., Methods: Cohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4-years of follow-up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all-cause deaths, were recorded., Results: Two thousand three hundred seventy-seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well-matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow-up (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.33-3.70, log-rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32-fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09-1.59, log-rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01-1.31), and mortality (HR: 1.25, 95% CI: 1.01-1.58) were also higher among AF patients with vascular dementia compared to AD., Conclusions: The two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Aims: This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia., Methods and Results: We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer's disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer's disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58-0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49-1.50)., Conclusion: Patients with AF have a higher incidence of all types of dementia, including Alzheimer's disease, vascular dementia, and a mixed type of dementia. Alzheimer's disease is less likely to occur in patients with AF undergoing catheter ablation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Damage to the cerebral vasculature can lead to vascular contributions to cognitive impairment and dementia (VCID). A reduction in blood flow to the brain leads to neuropathology, including neuroinflammation and white matter lesions that are a hallmark of VCID. Mid-life metabolic disease (obesity, prediabetes, or diabetes) is a risk factor for VCID which may be sex-dependent (female bias)., Methods: We compared the effects of mid-life metabolic disease between males and females in a chronic cerebral hypoperfusion mouse model of VCID. C57BL/6J mice were fed a control or high fat (HF) diet starting at ~ 8.5 months of age. Three months after diet initiation, sham or unilateral carotid artery occlusion surgery (VCID model) was performed. Three months later, mice underwent behavior testing and brains were collected to assess pathology., Results: We have previously shown that in this VCID model, HF diet causes greater metabolic impairment and a wider array of cognitive deficits in females compared to males. Here, we report on sex differences in the underlying neuropathology, specifically white matter changes and neuroinflammation in several areas of the brain. White matter was negatively impacted by VCID in males and HF diet in females, with greater metabolic impairment correlating with less myelin markers in females only. High fat diet led to an increase in microglia activation in males but not in females. Further, HF diet led to a decrease in proinflammatory cytokines and pro-resolving mediator mRNA expression in females but not males., Conclusions: The current study adds to our understanding of sex differences in underlying neuropathology of VCID in the presence of a common risk factor (obesity/prediabetes). This information is crucial for the development of effective, sex-specific therapeutic interventions for VCID., (© 2023. The Author(s).)

Background: Vascular dementia (VaD) is the most common type of dementia secondary to Alzheimer's disease. The pathologic mechanism of VaD is complex, and VaD still lacks a more objective diagnosis and evaluation method. Diffusion tensor imaging (DTI) can better detect the organizational structure and functional characteristics compared with any other diagnosis methods. Therefore, DTI has broad application in evaluating the severity and prognosis of VaD. This study aimed to assess the value of DTI in evaluating the cognitive function of patients with VaD., Methods: Authors searched Pubmed, Embase, and Cochrane Library, using the search terms, such as "diffusion tensor imaging," "DTI," "Vascular Dementia," "Arteriosclerotic Dementia," "Cognition," and "Cognitive." A voxel-based meta-analysis combined with quality statistics was performed, using the anisotropic effect-size version of the signed differential mapping method., Results: A total of 8 case-control studies were included in this meta-analysis. The sample size of patients ranged from 35 to 60, including 166 patients in the VaD group and 177 healthy individuals. The DTI imaging of the brain tissue of VaD patients was significantly different from that of healthy individuals., Conclusions: DTI imaging of the brain tissue of VaD patients was clearly different from that of healthy controls. Therefore it may be feasible to use DTI imaging as a diagnostic method for VaD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Dementia is a chronic progressive cognitive decline illness that results in functional impairment. Vascular dementia (VaD), second only to Alzheimer's disease (AD), is one of the most prevalent forms of dementia in the elderly (aged over 65 years), with a varied presentation and unpredictable disease development caused by cerebrovascular or cardiovascular illness. To get a better understanding of the changes occurring in the brain and to drive therapy efforts, new biomarkers for early and precise diagnosis of AD and VaD are required. In this review, Firstly, we describe the subtypes of vascular dementia, their clinical features, pathogenesis, genetics implemented, and their associated neuroimaging and biomarkers, while describing extensively the recent biomarkers discovered in the literature. Secondly, we describe some of the well-documented and other less-defined risk factors and their association and pathophysiology in relation to vascular dementia. Finally, we follow recent updates in the management of vascular dementia along with its association and differentiation from Alzheimer's disease. The aim of this review is to gather the scattered updates and the most recent changes in blood, CSF, and neuroimaging biomarkers related to the multiple subtypes of vascular dementia along with its association with Alzheimer's dementia and diabetes mellitus., Competing Interests: Conflict of Interest The authors declare no conflicts of interest, financial or otherwise., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We examined medical records to determine health conditions associated with dementia at varied intervals prior to dementia diagnosis in participants from the Baltimore Longitudinal Study of Aging (BLSA)., Methods: Data were available for 347 Alzheimer's disease (AD), 76 vascular dementia (VaD), and 811 control participants without dementia. Logistic regressions were performed associating International Classification of Diseases, 9th Revision (ICD-9) health codes with dementia status across all time points, at 5 and 1 year(s) prior to dementia diagnosis, and at the year of diagnosis, controlling for age, sex, and follow-up length of the medical record., Results: In AD, the earliest and most consistent associations across all time points included depression, erectile dysfunction, gait abnormalities, hearing loss, and nervous and musculoskeletal symptoms. Cardiomegaly, urinary incontinence, non-epithelial skin cancer, and pneumonia were not significant until 1 year before dementia diagnosis. In VaD, the earliest and most consistent associations across all time points included abnormal electrocardiogram (EKG), cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss. Atrial fibrillation, occlusion of cerebral arteries, essential tremor, and abnormal reflexes were not significant until 1 year before dementia diagnosis., Interpretation: These findings suggest that some health conditions are associated with future dementia beginning at least 5 years before dementia diagnosis and are consistently seen over time, while others only reach significance closer to the date of diagnosis. These results also show that there are both shared and distinctive health conditions associated with AD and VaD. These results reinforce the need for medical intervention and treatment to lessen the impact of health comorbidities in the aging population. ANN NEUROL 2023;93:805-818., (© 2022 American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Evaluation of the efficacy and safety of Prospect in the treatment of cognitive, behavioral and mental disorders in patients with vascular dementia (VSD)., Material and Methods: In a double-blind, placebo-controlled, parallel-group randomised clinical trial, 406 patients aged 60-85 years old with a diagnosis of mild/moderate vascular dementia (10-24 on the Mini-Mental State Examination (MMSE)) and without signs of depression (Cornell Scale for Depression in Dementia (CSDD) scores ≤10) were included. At Visit 1, complaints and medical history were collected, vital signs were recorded, cognitive impairment was assessed using MMSE and MoCA, NPI-C and CSDD were completed, and an MRI brain scan was performed. Patients were randomised into two groups: patients in group 1 received Prospekta in a dosage of 2 tablets two times a day for 24 weeks, and patients in group 2 received Placebo according to the study drug regimen., Results: Patients in both groups had no differences in demographic and baseline clinical characteristics. Administration of Prospekta for 24 weeks reduced cognitive impairment in patients with vascular dementia compared to the placebo group. The mean MoCA score increased from 17.0±3.6 [17.1±3.6] to 20.5±4.7 [20.4±4.7] in patients treated with Prospekta, whereas it increased from 17.3±3.7 [17.3±3.8] to 19.2±4.9 [19.2±5.0] in the Placebo group. Treatment with the medication also reduced the severity of neuropsychiatric symptoms as measured by the NPI-C scale. The mean score on this scale decreased from 57.0±26.7 [56.7±25.4] to 39.8±23.6 [39.8±23.5] in the Prospekta group and from 55.5±25.5 [55.3±24.4] to 42.8±27.6 [42.3±25.3] in the Placebo group. The difference in mean MoCA and NPI-C scores between the Prospekta and Placebo groups was statistically significant., Conclusion: Prospekta is an effective and safe drug for treating cognitive, behavioural and mental disturbances in patients with vascular dementia.

Background: Dementia presents a significant burden to patients and healthcare systems worldwide. Early and accurate diagnosis, as well as differential diagnosis of various types of dementia, are crucial for timely intervention and management. However, there is currently a lack of clinical tools for accurately distinguishing between these types., Objective: This study aimed to investigate the differences in the structural white matter (WM) network among different types of cognitive impairment/dementia using diffusion tensor imaging, and to explore the clinical relevance of the structural network., Methods: A total of 21 normal control, 13 subjective cognitive decline (SCD), 40 mild cognitive impairment (MCI), 22 Alzheimer's disease (AD), 13 mixed dementia (MixD), and 17 vascular dementia (VaD) participants were recruited. Graph theory was utilized to construct the brain network., Results: Our findings revealed a monotonic trend of disruption in the brain WM network (VaD > MixD > AD > MCI > SCD) in terms of decreased global efficiency, local efficiency, and average clustering coefficient, as well as increased characteristic path length. These network measurements were significantly associated with the clinical cognition index in each disease group separately., Conclusion: These findings suggest that structural WM network measurements can be utilized to differentiate between different types of cognitive impairment/dementia, and these measurements can provide valuable cognition-related information.

There is a paucity of research regarding the association between the risk of incident dementia and changes in smoking habits in the acute ischemic stroke population. We aimed to investigate the effects of smoking habit change on the risk of incident dementia in an ischemic stroke population using data from the Korean National Health Insurance Services Database. This nationwide population-based cohort study included 197,853 patients with ischemic stroke. The patients were divided into never smokers, former smokers, smoking quitters, sustained smokers, and new smokers, based on the 2-year change in smoking status between the two consecutive health examinations before and after the index stroke. The patients were followed up from the index date to 2018 to assess the development of dementia. Dementia was further categorized into Alzheimer's, vascular, and other types of dementia according to the International Classification of Diseases, Tenth Revision diagnosis. Multivariable Cox proportional hazards models were used to assess the association between changes in smoking habits and the risk of dementia. After a median of 4.04 years of follow-up, 19,595 (9.9%) dementia cases were observed. Among them, 15,189 (7.7%) were diagnosed with Alzheimer's disease dementia and 2719 (1.4%) were diagnosed with vascular dementia. After adjusting for covariates, including age, sex, alcohol intake habits, cigarette pack-year, regular physical activity, income, history of hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease, new smokers, sustained smokers, and smoking quitters were significantly associated with a higher risk of all-cause dementia than never smokers (adjusted hazard ratio [aHR] 1.395, 95% confidence interval [CI] 1.254-1.552; aHR 1.324, 95% CI 1.236-1.418; and aHR 1.170, 95% CI 1.074-1.275, respectively). Similar trends were observed for both Alzheimer's dementia and vascular dementia, but the association between new smokers and vascular dementia was not significant. The impact of smoking habit change was more prominent in the 40-65-year-old group. New and sustained smokers had a substantially higher risk of incident dementia after ischemic stroke than never smokers. Smoking quitters also had an elevated risk of incident dementia, but the detrimental effects were lower than those in new and sustained smokers., (© 2022. The Author(s).)

Background: Acupuncture can be used to treat vascular dementia (VD), but the underlying mechanism remains unclear. This study aimed to investigate the expression and clinical significance of microRNA-143-3p (miR-143-3p) in VD patients and explore whether acupuncture ameliorates VD by regulating miR-143-3p., Methods: Cognitive function and daily living ability in VD patients were assessed by mini-mental state examination, Hasegawa's dementia scale and activities of daily living scale, respectively. VD model of male Wistar rats was established using permanent bilateral common carotid artery occlusion. The expression level of miR-143-3p was measured by quantitative real-time PCR. Morris water maze test was used to assess the cognitive function of VD rat model. Receiver operating characteristic analysis was used to assess the diagnostic value of miR-143-3p in VD patients. Correlations between variables were analyzed by Pearson's correlation analysis., Results: Increased serum miR-143-3p expression in VD patients had a high diagnostic value to screen VD patients. Serum miR-143-3p level in VD patients after acupuncture treatment was decreased. After acupuncture treatment, serum miR-143-3p was negatively correlated with cognitive function and daily living ability in VD patients. miR-143-3p level was increased in VD rats, and the suppressive effects of acupuncture on miR-143-3p levels were relieved by miR-143-3p mimic. Overexpression of miR-143-3p reversed the ameliorative effect of acupuncture on cognitive functions of VD rats., Conclusion: Serum miR-143-3p expression is upregulated in VD patients and downregulated in VD patients after acupuncture treatment. Additionally, acupuncture treatment may attenuate cognitive impairments in VD by suppressing miR-143-3p.

Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not been investigated in VaD. Here, we tested whether pre-existing, circulating, high levels of TMAO could affect VaD-induced cognitive decline. TMAO (120 mg/kg) was given to rats for a total of 8 weeks, and these rats underwent a sham operation or bilateral common carotid artery (2VO) surgery after 4 weeks of treatment. Four weeks after surgery, the 2VO rats exhibited hippocampal-dependent cognitive function declines and synaptic plasticity dysfunction, accompanied by an increase in oxidative stress, neuroinflammation, and apoptosis. TMAO administration, which increased plasma and hippocampal TMAO at 4 weeks postoperatively, further aggravated these effects, resulting in exaggerated cognitive and synaptic plasticity impairment, though not within the Sham group. Moreover, TMAO treatment activated the NLRP3 inflammasome and decreased SIRT1 protein expression within the hippocampus. However, these effects of TMAO were significantly attenuated by the overexpression of SIRT1. Our findings suggest that TMAO increases oxidative stress-induced neuroinflammation and apoptosis by inhibiting the SIRT1 pathway, thereby exacerbating cognitive dysfunction and neuropathological changes in VaD rats.

Background: Previous studies found that cancer survivors had a reduced risk of dementia compared with the general population. However, these findings were uncertain because of survivor bias and a lack of stratification by cancer types. This current cohort study used data from the UK Biobank to explore these associations., Methods: Multivariable Cox regression analyses were used to examine the association of cancer status and the risk of dementia with its subtypes after adjusting for age and sex. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated as a measure of relative risk by comparing observed dementia incidence among cancer patients., Results: We included 263,151 participants in the observational analysis. During a median follow-up of 9.18 years, dementia was diagnosed in 472 individuals with cancer and 3685 individuals without cancer, respectively. Cancer patients had lower risks of dementia (hazard ratio: 0.89, confidence interval: 0.81-0.98) and its subtypes (Alzheimer's disease [AD]: 0.85 [0.74-0.98]; vascular dementia [VD]: 0.81 [0.66-0.99]) in the Cox regression adjusted for age and sex. Individuals with cancers in the male genital system had substantially reduced risks of dementia (0.66 [0.46-0.93]) and AD (0.53 [0.29-0.97]) than those with cancers in other systems. Moreover, non-melanoma skin cancer and prostate cancer were associated with a reduced risk of dementia (0.79 [0.62-0.99]; 0.69 [0.49-0.97]), but not with AD or VD (P>0.05)., Conclusions: The current study supported a negative association between cancer and dementia risk, and encourages further exploration of the mechanistic basis of this inverse relationship to improve understanding., (© 2022. The Author(s).)

Background and Purpose: Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation., Materials and Methods: Three hundred ninety patients with a diagnosis of no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia were recruited from the memory clinic. Cerebral microbleeds and lacunes were categorized into strictly lobar, strictly deep, and mixed-location and enlarged perivascular spaces into the centrum semiovale and basal ganglia. Total and region-specific white matter hyperintensity volumes were segmented using FreeSurfer. CBF ( n = 333) and the spatial coefficient of variation ( n = 390) were analyzed with ExploreASL from 2D-EPI pseudocontinuous arterial spin-labeling images in white matter (WM) and gray matter (GM). To analyze the effect of demographic and vascular risk factors as well as the location and severity of cerebral small-vessel disease markers on arterial spin-labeling parameters, we constructed linear regression models, whereas logistic regression models were used to determine the association between arterial spin-labeling parameters and cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia., Results: Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease, and smoking were associated with lower CBF and a higher spatial coefficient of variation. Higher numbers of lacunes and cerebral microbleeds were associated with lower CBF and a higher spatial coefficient of variation. Location-specific analysis showed mixed-location lacunes and cerebral microbleeds were associated with lower CBF. Higher total, anterior, and posterior white matter hyperintensity volumes were associated with a higher spatial coefficient of variation. No association was observed between enlarged perivascular spaces and arterial spin-labeling parameters. A higher spatial coefficient of variation was associated with the diagnosis of vascular cognitive impairment no dementia, Alzheimer's disease, and vascular dementia., Conclusions: Reduced CBF and an increased spatial coefficient of variation were associated with cerebral small-vessel disease, and more specifically lacunes, whereas cerebral microbleeds and white matter hyperintensities were associated with WM-CBF and GM spatial coefficient of variation. The spatial coefficient of variation was associated with cognitive impairment and dementia, suggesting that hypoperfusion might be the key underlying mechanism for vascular brain damage., (© 2022 by American Journal of Neuroradiology.)

Objective: To determine the effectiveness of a 13-week individual reminiscence therapy (RT) intervention on cognition, memory, executive function, mood, and quality of life of people with Alzheimer's disease and vascular dementia. Method: Non-protocolized analysis using data from a larger multicenter, single-blind, randomized, parallel two-arm RCT of RT for people with neurocognitive disorders. A sample of 148 people with probable Alzheimer's disease or vascular dementia attending 23 Portuguese institutions providing care and support services for older adults were selected. Intervention group (n = 74) received 26 individual RT sessions, twice a week for 13 weeks. Control group (n = 74) maintained their treatment as usual. Outcomes were global cognitive function (MMSE), memory (MAT), executive function (FAB), mood (GDS-15), and self-reported quality of life (QoL-AD). All participants were assessed at baseline (T0) and 15 weeks later (T1). Results: The results showed a significant effect of the intervention on global cognition (Group X Time interaction F (1, 128) = 10.542, p = .001, η p 2 = .076), memory ( F (1,128) = 9.881, p = .002, η p 2 = .072), and quality of life ( F (1,128) = 0.181, p = .671, η p 2 = .001), with medium effect sizes. A small effect on executive function ( F (1,127) = 11.118, p = .001, η p 2 = .080) was also found. No effects were found on depressive symptoms ( F (1,128) = 0.181, p = .671, η p 2 = .001). Conclusion: Individual RT may have beneficial effects on cognition and quality of life of people with Alzheimer's disease or vascular dementia.

Vascular contributions to cognitive impairment and dementia (VCID) secondary to chronic mild-moderate cerebral ischemia underlie a significant percentage of cases of dementia. We previously reported that either genetic deficiency of the complement C3a receptor (C3aR) or its pharmacological inhibition protects against cerebral ischemia in rodents, while others have implicated C3aR in the pathogenesis seen in rodent transgenic models of Alzheimer's disease. In the present study, we evaluated the role of complement C3a-C3aR signaling in the onset and progression of VCID. We utilized the bilateral common carotid artery stenosis (BCAS) model to induce VCID in male C57BL/6 wild-type and C3aR-knockout (C3aR -/- ) mice. Cerebral blood flow (CBF) changes, hippocampal atrophy (HA), white matter degeneration (WMD), and ventricular size were assessed at 4 months post-BCAS using laser speckle contrast analysis (LSCI) and magnetic resonance imaging (MRI). Cognitive function was evaluated using the Morris water maze (MWM), and novel object recognition (NOR), immunostaining, and western blot were performed to assess the effect of genetic C3aR deletion on post-VCID outcomes. BCAS resulted in decreased CBF and increased HA, WMD, and neurovascular inflammation in WT (C57BL/6) compared to C3aR -/- (C3aR-KO) mice. Moreover, C3aR -/- mice exhibited improved cognitive function on NOR and MWM relative to WT controls. We conclude that over-activation of the C3a/C3aR axis exacerbates neurovascular inflammation leading to poor VCID outcomes which are mitigated by C3aR deletion. Future studies are warranted to dissect the role of cell-specific C3aR in VCID., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The fat-to-muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex-specific associations between total and regional FMR and incident dementia., Methods: A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis., Results: During a median 8.65 years of follow-up, we documented 2 225 incident all-cause dementia cases, including 836 AD and 468 VD cases. There was an L-shaped association between whole body FMR and all-cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non-linear <0.001 in men and women), where all-cause dementia risk decreased steeply with increasing FMR and levelled off at around the medians (0.35 in men, 0.61 in women) with a hazard ratio (HR) of 0.78 (95% CI: 0.64, 0.96; P = 0.019) and 0.60 (0.47, 0.77; <0.001) per 1 standard deviation (SD) increase in men and women, respectively. Compared with other body parts, FMR of the leg showed the strongest inverse associations [HR (95% CI; P) per 1 SD below the medians: 0.60 (0.48, 0.75; <0.001); 0.61 (0.47, 0.79; <0.001) in men and women, respectively]. Specifically, the inverse associations of whole body FMR on all-cause dementia risk were significant only among participants over the age of 60 (P for trend <0.001). Multivariable adjusted Cox models showed inverse associations of whole body FMR with AD in men only (P for trend = 0.003), whereas no statistically significant decrease was detected in VD among men and women., Conclusions: Our analyses provide strong evidence for L-shaped associations of total and regional FMR with the development of dementia among participants aged 60 years or older independent of overall obesity., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is the second leading cause of dementia after Alzheimer's disease. Cognitive consequences after ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting the search for potential agents. The keyword "vascular dementia" was used to search ClinicalTrials.gov to determine agents represented in phases I, II, III, and IV. The agents were classified on the basis of their mechanisms. Of the 17 randomized controlled trials meeting our inclusion criteria, 9 were completed in the past 10 years, and 8 are ongoing or in the planning stages. We also identified one trial in phase I, nine in phase II, six in phase III, and one in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer's dementia. Drug trials on vascular dementia overlap with drug trials targeting functional outcomes in cerebrovascular disease. International pharmaceutical companies' investment in new drugs targeting VCI and vascular dementia remains insufficient.

Alzheimer's disease is the most common form of dementia, and the prodromal phases of Alzheimer's disease can last for decades. Vascular dementia is the second most common form of dementia and is distinguished from Alzheimer's disease by evidence of previous stroke or hemorrhage and current cerebrovascular disease. A compiled group of vascular-related dementias (vascular dementia and unspecified dementia) is often referred to as non-Alzheimer dementia. Recent evidence indicates that preventing dementia by lifestyle interventions early in life with a focus on reducing cardiovascular risk factors is a promising strategy for reducing future risk. Approximately 40% of dementia cases is estimated to be preventable by targeting modifiable, primarily cardiovascular risk factors. The aim of this review is to describe the association between risk factors for atherosclerotic cardiovascular disease and the risk of Alzheimer's disease and non-Alzheimer dementia by providing an overview of the current evidence and to shed light on possible shared pathogenic pathways between dementia and cardiovascular disease. The included risk factors are body mass index (BMI); plasma triglyceride-, high-density lipoprotein (HDL) cholesterol-, low-density lipoprotein (LDL) cholesterol-, and total cholesterol concentrations; hypertension; diabetes; non-alcoholic fatty liver disease (NAFLD); physical inactivity; smoking; diet; the gut microbiome; and genetics. Furthermore, we aim to disentangle the difference between associations of risk factors in midlife as compared with in late life.

Background: Studies investigating the association between migraine and dementia have reported inconsistent findings. This study aimed to evaluate whether patients with migraine have an increased risk of dementia compared to individuals without migraine., Methods: We obtained data from the 2002-2019 Korean National Health Insurance Health Screening Cohort. Non-migraine controls were selected using a 1:1 risk-set matching with a time-dependent propensity score. The main outcome was the development of all-cause dementia, and the secondary outcome was the development of each cause of dementia (Alzheimer's, vascular, mixed or other specified, and unspecified dementia). The incidence rate of dementia was calculated using Poisson regression, and the association between migraine and dementia was evaluated using Cox proportional hazards regression., Results: Among 88,390 participants, 66.1% were female, and the mean baseline age was 55.3 ± 9.4 years. During the study period, dementia cases were identified in 4,800 of the 44,195 patients with migraine and 3,757 of the 44,915 matched controls. The incidence rate of dementia was 139.6 (95% confidence interval [CI], 135.7-143.5) and 107.7 (95% CI, 104.3-111.1) cases per 10,000 person-years in patients with migraine and matched controls, respectively. Patients with migraine had a 1.30 (hazard ratio [HR], 1.30; 95% CI, 1.25-1.35), 1.29 (HR, 1.29; 95% CI, 1.23-1.35), 1.35 (HR, 1.35; 95% CI, 1.19-1.54), 1.36 (HR, 1.36; 95% CI, 1.00-1.83), and 1.30 (HR, 1.30; 95% CI, 1.17-1.45) times higher risk of developing all-cause dementia, Alzheimer's dementia, vascular dementia, mixed or other specified dementias, and unspecified dementia than their matched controls, respectively., Conclusion: Our results suggest that migraine is associated with an increased risk of subsequent dementia. Further research is warranted to confirm these findings and to reveal the underlying mechanisms., (© 2022. The Author(s).)

Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) and dementia share common risk factors including metabolic disorders. However, whether NAFLD is associated with dementia risk is unclear. We investigated the association between NAFLD and dementia risk as well as the role of cardiovascular complications including heart disease and stroke., Methods: In this population-based matched cohort study, we identified all Swedish patients aged 65 years or older with NAFLD identified from the National Patient Register (NPR) between 1987 and 2016. These were matched with up to 10 reference individuals from the general population on age, sex, and municipality at the year of diagnosis. Incident dementia diagnosis was derived from the NPR or the Cause of Death Register until 2016. Adjusted hazard ratios (aHRs) and 95% CIs were estimated with Cox regression models., Results: A total of 2,898 patients with NAFLD and 28,357 matched controls were identified (median age at entry, interquartile range [IQR], 70 [8]; 55.1% female). During a median follow-up of 5.5 years (IQR: 8.5 years), 145 (5.0%) patients with NAFLD and 1,291 (4.6%) reference individuals were diagnosed with dementia. Compared with the reference individuals, patients with NAFLD had higher rates of dementia (aHR 1.38, 95% CI 1.10-1.72) and vascular dementia (aHR 1.44, 95% CI 0.96-2.23, p = 0.07). Comorbid NAFLD and either heart disease (aHR 1.50 95% 1.08-2.05) or stroke (aHR 2.60 95% CI 1.95-3.47) conferred a greater risk of dementia., Discussion: NAFLD had a modest association with increased rates of dementia. This was stronger among patients with NAFLD diagnosed with cardiovascular comorbidities., Classification of Evidence: This study provides Class II evidence that nonalcoholic fatty liver disease is associated with the development of vascular and nonvascular dementia., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose of Review: Metabolic syndrome is associated with an increased risk of vascular cognitive impairment or, in the more extreme, vascular dementia. Animal models are used to investigate the relationship between pathology and behaviour. This review summarizes the latest understanding of the role of the hippocampus and prefrontal cortex in vascular cognitive impairment, the influence of inflammation in this association while also commenting on some of the latest interventions proposed., Recent Findings: Models of vascular cognitive impairment and vascular dementia, whether they develop from an infarct or non-infarct base, demonstrate increased neuroinflammation, reduced neuronal function and deficits in prefrontal and hippocampal-associated cognitive domains. Promising new research shows agents and environmental interventions that inhibit central oxidative stress and inflammation can reverse both pathology and cognitive dysfunction. While preclinical studies suggest that reversal of deficits in vascular cognitive impairment models is possible, replication in patients still needs to be demonstrated., (© 2022. The Author(s).)

Background and Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and early-onset dementia. We determined the prevalence of vascular cognitive impairment (VCI) in a group of patients with CADASIL and investigated which factors were associated with VCI risk, including clinical, genetic, and MRI parameters., Methods: Cognition was assessed in patients with genetically confirmed CADASIL (n = 176) and healthy controls (n = 265) (mean [SD] age 50.95 [11.35] vs 52.37 [7.93] years) using the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA). VCI was defined according to previously validated cutoffs. We determined the prevalence of VCI and its associations with clinical risk factors, mutation location (epidermal growth factor-like repeats [EGFr] 1-6 vs EGFr 7-34), and MRI markers of small vessel disease., Results: VCI was more common in patients with CADASIL than in controls; 39.8 vs 10.2% on the BMET and 47.7% vs 19.6% on the MOCA. Patients with CADASIL had worse performance across all cognitive domains. A history of stroke was associated with VCI on the BMET (OR 2.12, 95% CI [1.05, 4.27] p = 0.04) and MoCA (OR 2.55 [1.21, 5.41] p = 0.01), after controlling for age and sex. There was no association of VCI with mutation site. Lacune count was the only MRI parameter independently associated with VCI on the BMET (OR: 1.63, 95% CI [1.10, 2.41], p = 0.014), after controlling for other MRI parameters. These associations persisted after controlling for education in the sensitivity analyses., Discussion: VCI is present in almost half of the patients with CADASIL with a mean age of 50 years. Stroke and lacune count on MRI were both independent predictors of VCI on the BMET., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: There is limited information on new onset poststroke dementia (NPSD) in sub-Saharan Africa (SSA). We estimated incidence, cumulative incidence, risk factors and outcome of NPSD at 1 year in Nigerian survivors of a first-ever stroke., Methods: Hospital-based prospective observational study. Assessments for global cognition, learning, memory, executive and activities of daily life (ADL) functioning were conducted at 3 poststroke timepoints (Baseline, 3- and 12 months). NPSD was ascertained according to the "National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria." Outcomes were assessed using the modified Rankin Scale (mRS), center for epidemiologic studies depression scale (CES-D 10), health related quality of life in stroke patients (HRQOLISP-26) and caregivers strain index (CSI)., Results: Among 144 stroke survivors who were free of dementia at baseline, we found a 1-year cumulative incidence of 4.52% (95% C.I = 3.20, 6.39). In multivariate Cox regression analyses, diabetes was associated with NPSD (Hazard Ratio = 2.10, 95% CI = 1.02, 4.35). NPSD at 3 months was independently associated with motor decline [Mean difference (MD) in mRS = 1.6, 95% C.I = 0.9, 2.3)], depression (MD in CES-D = 2.9, 95% C.I = 0.3, 5.4), caregivers burden (MD in CSI = 1.2, 95% C.I = 0.5, 1.8), and poor quality of life (MD in HRQOLISP-26 = -11.2, 95% C.I = -15.7, -6.8) at 1 year., Conclusion: Approximately 4.5% of stroke survivors in Nigeria had NPSD at 1 year. Diabetes, which can be prevented, represent a primary prevention target for NPSD and its consequences in SSA.

Background: Carotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography., Objectives: The Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques., Study Design: We will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727)., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Introduction: Cognitive decline and dementia recognize multiple risk factors and pathophysiological mechanisms, often involved simultaneously with complex interactions. Several studies have shown that both arterial hypertension and hypotension are associated with a greater risk of cognitive decline and dementia, but clinical evidence on this point is conflicting. Our aim was to conduct an umbrella review on cognitive function, dementia, and blood pressure, with particular attention to epidemiological, prognostic and therapeutic aspects., Evidence Acquisition: We conducted a dedicated literature search on PubMed for systematic reviews and meta-analyses that focused on arterial pressure, hypertension, hypotension and similar conditions, and cognitive function, cognitive decline and dementia. The internal validity of systematic reviews and meta-analyses was formally analyzed using the OQAQ tool. The umbrella review was planned in accordance with current international recommendations and was described as specified by the PRISMA guidelines., Evidence Synthesis: Seventeen systematic reviews (including 13 meta-analyses) were included, for a total of 675 clinical studies and over 1 million patients. Hypertension results to be associated with a lower risk of Alzheimer's dementia, greater risk of vascular dementia and greater risk of cognitive decline. Orthostatic hypotension seems to be associated with greater risk of Alzheimer's dementia, vascular dementia and dementia of Parkinson's disease. Therapy with acetylcholinesterase inhibitors produces lower risk of cardiovascular events, greater risk of hypertension and greater risk of bradycardia, while the anti-hypertensive therapy leads to a lower risk of dementia of all types and lower risk of cognitive decline., Conclusions: To date, the evidence on the relationship between blood pressure, cognitive decline and dementia provides somewhat heterogeneous data. Further studies are clearly needed, with explicit inclusion criteria as objective as possible, adequate follow-up and precise characterization of implemented cardiovascular and cognitive treatments.

Objectives: To conduct a comprehensive systematic review and meta-analysis to explore the correlation between migraine and the risk of dementia., Methods: The PubMed, EMBASE, and Cochrane library databases were searched systematically. We selected cohort studies (prospective and retrospective) and case-control studies that reported migraine in patients with dementia, including vascular dementia. The pooled effects were analyzed to evaluate relative risk with 95% confidence intervals., Results: In total, nine studies (two case-control and seven cohort studies) including 291,549 individuals were identified. These studies indicated that people with migraine (relative risk = 1.33; 95% confidence interval: 1.16-1.53) have an increased risk of all-cause dementia. Additionally, the pooled results of four studies showed that migraine is associated with an increased risk of vascular dementia (relative risk = 1.85; 95% confidence interval: 1.22-2.81; P = 0.004)., Conclusions: Data from observational studies suggest that migraine may be a risk factor for dementia, particularly vascular dementia. More studies are warranted to explore the association between migraine and dementia and the potential common pathophysiological mechanisms., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: No population-based cohort study investigated a potential inverse association between long-term low-dose acetylsalicylic acid (ASA) use and all-cause dementia and its two most common sub-types Alzheimer's disease (AD) and vascular dementia (VD) so far., Methods: Cox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of low-dose ASA use with all-cause dementia, AD, and VD incidence in community-dwelling older adults from the German ESTHER study (N = 5258) and the UK Biobank (N = 305,394). Inclusion criteria were age of 55 years or older and completed drug assessment. Meta-analyses of the individual participant data from the two prospective cohort studies were performed., Results: Four hundred seventy-six cases of all-cause dementia, 157 cases of AD, and 183 cases of VD were diagnosed over a median of 14.3 years of follow-up in ESTHER. In the UK Biobank, 5584 participants were diagnosed with all-cause dementia, 2029 with AD, and 1437 with VD over a median of 11.6 years. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia (hazard ratio (HR) [95% confidence interval (CI)]: 0.96 [0.93 to 0.99]). The strongest protective effect of low-dose ASA was observed in participants with coronary heart disease (CHD) in both cohorts, and a significant interaction was detected. In particular, in meta-analysis, a 31% reduction in hazard for AD, 69% for VD and 34% for all-cause dementia were observed (HR [95% CI]: 0.69 [0.59 to 0.80], 0.31 [0.27 to 0.35], 0.46 [0.42 to 0.50], respectively). Furthermore, compared to non-users, users of low-dose ASA for 10 years or longer (who likely use it because they have CHD or a related diagnosis putting them at an increased risk for cardiovascular events) demonstrated a strong protective effect on all dementia outcomes, especially for VD (HR [95% CI]: 0.48 [0.42 to 0.56]) whereas no protective associations were observed with shorter low-dose ASA use., Conclusions: The protective potential of low-dose ASA for all-cause dementia, AD, and VD seems to strongly depend on pre-existing CHD and the willingness of patients to take it for a minimum of ten years., (© 2022. The Author(s).)

Vascular dementia (VD) is the second largest type of dementia after Alzheimer's disease. At present, the pathogenesis is complex and there is no effective treatment. Floralozone has been shown to reduce atherosclerosis in rats caused by a high-fat diet. However, whether it plays a role in VD remains elusive. In the present study, the protective activities and relevant mechanisms of Floralozone were evaluated in rats with cognitive impairment, which were induced by bilateral occlusion of the common carotid arteries (BCCAO) in rats. Cognitive function, pathological changes and oxidative stress condition in the brains of VD rats were assessed using Neurobehavioral tests, Morris water maze tests, hematoxylin-eosin staining, Neu N staining, TUNEL staining, Golgi staining, Western blot assay and antioxidant assays (MDA, SOD, GSH), respectively. The results indicated that VD model was established successfully and BCCAO caused a decline in spatial learning and memory and hippocampal histopathological abnormalities of rats. Floralozone (50, 100, 150 mg/kg) dose-dependently alleviated the pathological changes, decreased oxidative stress injury, which eventually reduced cognitive impairment in BCCAO rats. The same results were shown in further experiments with neurobehavioral tests. At the molecular biological level, Floralozone decreased the protein level of transient receptor potential melastatin-related 2 (TRPM2) in VD and normal rats, and increased the protein level of NR2B in hippocampus of N-methyl-D-aspartate receptor (NMDAR). Notably, Floralozone could markedly improved learning and memory function of BCCAO rats in Morris water maze (MWM) and improved neuronal cell loss, synaptic structural plasticity. In conclusion, Floralozone has therapeutic potential for VD, increased synaptic structural plasticity and alleviating neuronal cell apoptosis, which may be related to the TRPM2/NMDAR pathway., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: We investigated the association between interval changes in physical activity (PA) and dementia risk among patients with new-onset type 2 diabetes., Research Design and Methods: We identified 133,751 participants newly diagnosed with type 2 diabetes in a health screening (2009-2012), with a follow-up health screening within 2 years (2010-2015). PA level changes were categorized into continuous lack of PA, decreaser, increaser, and continuous PA groups. Dementia was determined using dementia diagnosis codes and antidementia drug prescriptions., Results: During the median follow-up of 4.8 years, 3,240 new cases of all-cause dementia developed. Regular PA was associated with lower risks of all-cause dementia (adjusted hazard ratio [aHR] 0.82; 95% CI 0.75-0.90), Alzheimer disease (AD) (aHR 0.85; 95% CI 0.77-0.95), and vascular dementia (VaD) (aHR 0.78; 95% CI 0.61-0.99). Increasers who started to engage in regular PA had a lower risk of all-cause dementia (aHR 0.86; 95% CI 0.77-0.96). Moreover, the risk was further reduced among those with continuous regular PA: all-cause dementia (aHR 0.73; 95% CI 0.62-0.85), AD (aHR 0.74; 95% CI 0.62-0.88), and VaD (aHR 0.62; 95% CI 0.40-0.94). Consistent results were noted in various subgroup analyses., Conclusions: Regular PA was independently associated with lower risks of all-cause dementia, AD, and VaD among individuals with new-onset type 2 diabetes. Those with continuous regular PA and, to a lesser extent, those who started to engage in regular PA had a lower risk of dementia. Regular PA should be encouraged to prevent dementia in high-risk populations and those with new-onset type 2 diabetes., (© 2022 by the American Diabetes Association.)