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BACKGROUND: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. METHODS: Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. RESULTS: At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience.

Bilingualism is thought to confer advantages in executive functioning, thereby contributing to cognitive reserve and a later age of dementia symptom onset. While the relation between bilingualism and age of onset has been explored in Alzheimer's dementia, there are few studies examining bilingualism as a contributor to cognitive reserve in frontotemporal dementia (FTD). In line with previous findings, we hypothesized that bilinguals with behavioral variant FTD would be older at symptom onset compared to monolinguals, but that no such effect would be found in patients with nonfluent/agrammatic variant primary progressive aphasia (PPA) or semantic variant PPA. Contrary to our hypothesis, we found no significant difference in age at symptom onset between monolingual and bilingual speakers within any of the FTD variants, and there were no notable differences on neuropsychological measures. Overall, our results do not support a protective effect of bilingualism in patients with FTD-spectrum disease in a U.S. based cohort.

INTRODUCTION: The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood. METHODS: Thirty-five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults [TOFHLA]), structural and resting state functional magnetic resonance imaging, and an episodic memory test (Free and Cued Selective Reminding Test). Illiteracy was defined as a TOFHLA score < 53. We evaluated the correlation between hippocampal connectivity at rest and both free recall and literacy scores. RESULTS: Participants were mostly female (57.1%) and self-declared as being Black individuals (84.8%), with a median age of 50 years. The median TOFHLA literacy score was 28.0 [21.0; 42.5] out of 100 points and the median free recall score was 30.0 [26.2; 35] out of 48 points. The median gray matter volume of both the left and right hippocampi was 2.3 [2.1; 2.4] cm3. We observed a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. The right hippocampal connectivity positively correlated with the literacy scores (β = 0.58, P = 0.008). There was no significant association between episodic memory and hippocampal connectivity. Neither memory nor literacy scores correlated with hippocampal gray matter volume. DISCUSSION: Low literacy levels correlated with hippocampal connectivity in illiterate adults. The lack of association with memory scores might be associated with low brain reserve in this sample. HIGHLIGHTS: A significant link was found between health literacy and hippocampal connectivity.Enhanced hippocampus- ventromedial prefrontal cortex connectivity suggests potential cognitive reserve improvement.Higher cognitive reserve may protect against hippocampal atrophy and neurodegeneration.Health literacy improvements could help prevent cognitive impairment in illiterate populations.Study highlights importance of considering structural racism in brain connectivity research.

UNLABELLED: The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve. OBJECTIVE: This manuscript aims to explore the relationship between SES and learning, as well as cognitive outcomes, in an older illiterate population. METHODS: This six-month clinical trial (NCT04473235) involved 108 participants, of which 77 concluded all assessments, enrolled in late-life basic education. SES assessments included Quality of Urban Living Index, Municipal Human Development Index and Household SES calculated for each participant. Cognitive assessments encompassed the Free and Cued Selective Reminding Test (FCSRT), a word list to assess reading, and the Beta III matrix. RESULTS: The sample consisted primarily of women, with a mean age of 58.5. Participants improved their reading (p=0.01) and their FCSRT (p=0.003). Regarding episodic memory, women outperformed men (p=0.007) and younger participants improved more than their older counterparts (p=0.001). There was no association observed between SES and cognitive outcomes. CONCLUSION: Irrespective of SES, participants demonstrated positive outcomes after attending basic education. These findings highlight that late life education could be an important non-pharmacologic preventative measure, especially in LMICs.

Background: Reserves' mechanisms explain inconsistencies between accumulation of neuropathological damage and clinical manifestations. Leisure activities are believed to promote reserves. Objective: This study evaluates whether cognitive, social, and physical leisure activities performed over life-span predict current cognitive functioning in normal aging and Alzheimer's disease (AD) continuum. Methods: 35 AD, 24 amnestic-Mild Cognitive Impairment (a-MCI) patients, 21 individuals with subjective cognitive complaint (SCD), and 25 controls underwent a questionnaire developed to quantify leisure activities in different life periods, the Addenbrooke's Cognitive Examination-Revised (ACE-R), and T1-weighted 3T-MRI scans for brain volumetrics and cortical thickness quantification. Partial/total leisure activities' scores and demographic and brain variables were entered as predictors, while ACE-R scores as dependent variables in linear regression analyses. Results: Current level of cognition was predicted by (i) social and physical activities performed in middle age and current cognitive activity in AD; (ii) cognitive and social activities performed in middle age, current age and cortical thickness in a-MCI; (iii) recreational activities the set of lifetime, current age, and brain features in SCD; (iv) education and the set of lifetime leisure activities over lifespan in controls. Conclusions: This study shows a funnel effect due to gradual reduction of stimulatory activities in the transition from healthy aging to AD. Reserve indices taking into account different types of stimulatory activities allow to capture even smallest residual effects of reserves accumulated over lifespan, until their complete depletion at advanced AD stages. These results may help target tailored interventions during normal and pathological aging. [ABSTRACT FROM AUTHOR]

Background: Females have a higher age-adjusted incidence of Alzheimer's Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building cognitive reserve, particularly through stimulating avocational activities and occupational attainment presents a crucial, underexplored, dementia prevention approach for mid-life. It is currently unknown, however, whether modifiable lifestyle factors can protect against AD processes, from mid-life, differentially for females and males who carry inherited risk for late-life dementia. To address this gap, this study investigated the impact of biological sex and APOE4 carrier status on the relationship between stimulating activities, occupational attainment, and cognition in mid-life. Methods: We leveraged the PREVENT–Dementia program, the world's largest study investigating the origins and early diagnosis of dementia in mid-life at-risk individuals (N = 700; 40–59 years). Cognitive performance was measured using the Cognito Battery and the Visual Short Term Memory Binding task. Mid-life specific reserve contributors were assessed via the Lifetime of Experiences Questionnaire. Results: Females had significantly better episodic and relational memory (p < 0.001), and lower occupational attainment than males (p < 0.001). Engagement in stimulating activities was positively associated with episodic and relational memory, regardless of sex and APOE4 status (β = 0.05, CI 0.03–0.07, p < 0.001). APOE4 carriers showed significant sex differences in the association between occupational attainment and episodic and relational memory (β = 0.38, CI 0.12–0.63, p = 0.003). APOE4 carrier females with higher occupational attainment showed better cognition (β = 0.16, CI -0.002–0.32, p = 0.053), whereas APOE4 carrier males showed the opposite effect (β = -0.20, CI -0.40 – -0.001, p = 0.049). Conclusion: Our findings suggest that occupational attainment in mid-life contributes to cognitive reserve against inherited risk of dementia in females, but not males. They highlight the need for high precision approaches that consider biological sex and APOE4 carrier status to inform Alzheimer's disease prevention strategies and clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods: A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 (C9orf72) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results: For the ALS group, the statistical model explained 38.8% of variance in ECAS total (p < 0.001), 59.4% of executive functions (p < 0.001), and 55% of behavioral symptoms (p < 0.001). For controls, it accounted for 52.8% of variance in ECAS total (p < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups (p < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls (p = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom' predictor in patients (p = 0.009). Conclusion: This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS. [ABSTRACT FROM AUTHOR]

Background: As the population ages, the concept of frailty becomes increasingly relevant and may be considered a precursor between aging and the development of dementia in later life. Similarly, the construct of cognitive reserve (CR) is an accepted model of cognitive resilience that may account for individual differences in trajectories of brain aging, mitigating the clinical expression of dementia. Objective: We aim to estimate the role of CR and frailty in moderating the prediction of dementia in the population aged over 80 who are attending an Italian outpatient memory clinic. Methods: Comprehensive Geriatric Assessment, Clinical Frailty Scale (CFS) to screen for frailty, and Cognitive Reserve Index questionnaire (CRIq) to evaluate CR, were used to assess patients systematically. We performed multivariate logistic regression to assess associations with dementia. Model performance and interaction between frailty and cognitive reserve were then evaluated. Results: 166 patients were consecutively enrolled (mean age was 85.7 years old, females composed 68%); 25% had a diagnosis of amnestic mild cognitive impairment, and 75% had a diagnosis of dementia. Multivariate regression analysis showed that CRIq and CFS were the main clinical assessment tools associated with the presence of dementia, even after collinearity adjustment. No significant interaction of CFS*CRIq was found. Conclusions: To our knowledge, this is the first study to investigate the association between CR, frailty, dementia, and their related interacting terms in a real-world population of very old patients. Our findings may suggest that both CR and frailty shape an individual's resilience throughout their lifetime. This may potentially counteract the effects of brain neuropathology, in line with the hypothesis that meaningful associations exist between CR, frailty, and cognition in later life. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study examines the role of lifestyle factors in cognitive reserve among older adults, focusing on the moderating effect of apolipoprotein E (APOE) ε4 status. METHODS: Data from 157 participants aged 45 and older from the Healthy Brain Initiative (HBI) were analyzed. Cognitive reserve was estimated using residual scores from Cognivue Clarity tests after accounting for brain atrophy and white matter hyperintensities (WMHs). Lifestyle factors included education, occupational attainment, physical activity, social engagement, diet, and mindfulness. Structural equation models were conducted to assess interactions. RESULTS: Significant interactions were found between APOE ε4 status and mindfulness and social engagement on cognitive reserve, indicating stronger associations for APOE ε4 carriers. DISCUSSION: APOE ε4 carriers may benefit more from certain lifestyle factors, potentially through stress reduction and anti‐inflammatory pathways. These findings support integrating APOE ε4 genetic screening into personalized prevention strategies to enhance interventions aimed at preserving cognitive function and delaying dementia onset in at‐risk populations. Highlights: Mindfulness and social engagement have increased cognitive reserve in APOE ε4 carriers.Study uses residual scores from Cognivue Clarity tests to estimate cognitive reserve.APOE ε4 carriers show stronger associations with certain lifestyle factors on cognitive reserve.Personalized interventions could enhance cognitive resilience in genetically at‐risk populations.Comprehensive assessment of multiple lifestyle factors highlights targeted intervention benefits. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We investigated distinctive factors associated with cognitive reserve (CR) based on education level. METHODS: Among 1247 participants who underwent neuropsychological assessment, amyloid positron emission tomography, and brain magnetic resonance imaging, 336 participants with low education (≤6 years) and 697 with high education (≥12 years) were selected. CR was measured as the difference between the predicted and observed value of cognitive function based on cortical thickness. Multiple linear regression was conducted in each group after controlling for age and sex. RESULTS: In the low‐education group, low literacy, long sleep duration(>8 h/day), and diabetes were negatively associated with CR, whereas cognitive and physical activity were positively associated with CR. In the high‐education group, cognitive activity was positively related to CR, whereas low literacy, long sleep duration (> 8 h/day), and depression were negatively related to CR. DISCUSSION: This study provides insights into different strategies for enhancing CR based on educational background. Highlights: Factors associated with cognitive reserve (CR) varied according to the education level.Diabetes and physical activity were associated with CR in the low‐education group.Depression was related to CR in the high‐education group.Low literacy, sleep duration, and cognitive activity were associated with CR in both groups.Dementia‐prevention strategies should be tailored according to educational level. [ABSTRACT FROM AUTHOR]

Cognitive training (CT) programs aim to improve cognitive performance and impede its decline. Thus, defining the characteristics of individuals who can benefit from these interventions is essential. Our objectives were to assess if the cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers) and/or hippocampal volume might predict the effectiveness of a CT program. Participants were older adults without dementia (n = 226), randomized into parallel experimental and control groups. The assessment consisted of a neuropsychological protocol and additional data regarding total intracranial, gray matter, left/right hippocampus volume; APOE genotype; and Cognitive Reserve (CR). The intervention involved multifactorial CT (30 sessions, 90 min each), with an evaluation pre- and post-training (at six months); the control group simply following the center's routine activities. The primary outcome measures were the change in cognitive performance and the predictors of change. The results show that APOE-e4 non-carriers (79.1%) with a larger left hippocampal volume achieved better gains in semantic verbal fluency (R2 =.19). Subjects with a larger CR and a greater gray matter volume better improved their processing speed (R2 =.18). Age was correlated with the improvement in executive functions, such that older age predicts less improvement (R2 =.07). Subjects with a larger left hippocampal volume achieved more significant gains in general cognitive performance (R2 =.087). In conclusion, besides the program itself, the effectiveness of CT depends on age, biological factors like genotype and brain volume, and CR. Thus, to achieve better results through a CT, it is essential to consider the different characteristics of the participants, including genetic factors. Trial registration: Trial retrospectively registered on January 29th, 2020—(ClinicalTrials.gov -NCT04245579). [ABSTRACT FROM AUTHOR]

As the literature related to cognitive reserve (CR) in individuals with frontotemporal dementia (FTD) is only emerging, a clear consensus on the relationship among CR proxies, brain status, and clinical performance has not been reached. The primary aim of this systematic review was to examine the relationship among sociobehavioral proxies of CR, brain status, and clinical performance in individuals with various types of FTD. Additionally, characteristics of patient population, sociobehavioral proxies, disease severity tools, and brain status measures used were identified. The systematic review was conducted using comprehensive search terms in Medline, PsychINFO, PubMed, and Web of Science. Eligibility criteria were for studies to include at least one CR and one brain status measure for individuals with FTD, be published in a peer-reviewed journal, and be published in English. The Newcastle-Ottawa Quality Assessment Scale was used to assess study quality and bias risk. A total of 237 titles and abstracts were screened, with 13 studies meeting inclusion criteria. Together, these studies report 1,423 participants with FTD. Based on the included studies, partial support was demonstrated for CR in individuals with FTD when education, occupation, and leisure were utilized as CR proxies. The variability in results among studies could be related to the different tools used to measure CR, brain status, and disease severity. This review provides recommendations for future studies: incorporating longitudinal designs, in depth neuropsychological testing, consistent disease duration measure, and transparant statistical output reporting. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives To investigate the determinants of resilience phenotype in aging, operationalized as the maintenance of cognitive, physical, and psychological health in very old individuals (80+), we investigated the structure and interrelated impact of the main resilience-enhancing factors, which are usually studied in separate research fields. Methods Participants were older adults without dementia recruited for the fifth wave of the InveCe.Ab population-based cohort study (aged 83–87 years). Multidimensional evaluation comprised blood sampling, social and lifestyle survey, and geriatric and neuropsychological assessment. We classified resilient individuals as displaying normal cognition, functional independence, and mental health. First, we performed exploratory factor analysis (EFA) to examine the underlying structure of the relevant cognitive, lifestyle, physical, and psychological resilience-enhancing factors. The factors obtained were included as predictors of the resilience phenotype in the logistic regression model, controlling for sociodemographic and cumulative exposure to physical and psychosocial stressors, including COVID-19 infection. Results Among the 404 enrolled participants, 153 (38%) exhibited the resilience phenotype. EFA resulted in the identification of six factors (59% of variance): cognitive reserve, affective reserve, insecure attachment, current lifestyle, physical reserve, and avoidant attachment. Among these factors, cognitive reserve, affective reserve, and current lifestyle significantly and independently predicted resilience status, controlling for cumulative exposure to age-related stressors and COVID-19 infection. Discussion Our findings showed that, even in very old age, both early and late life modifiable factors affect individuals' ability to adapt to the aging process, thus confirming the importance of a life-course approach to improve health outcomes in the aged population. Clinical Trials Registration Number NCT01345110 [ABSTRACT FROM AUTHOR]

Background: State-of-the-art stroke treatment significantly reduces lesion size and stroke severity, but it remains unclear whether these therapeutic advances have diminished the burden of post-stroke cognitive impairment (PSCI). Aims: In a cohort of patients receiving modern state-of-the-art stroke care including endovascular therapy, we assessed the frequency of PSCI and the pattern of domain-specific cognitive deficits, identified risk factors for PSCI, and determined the impact of acute PSCI on stroke outcome. Methods: In this prospective monocentric cohort study, we examined patients with first-ever anterior circulation ischemic stroke without pre-stroke cognitive decline, using a comprehensive neuropsychological assessment ⩽10 days after symptom onset. Normative data were stratified by demographic variables. We defined PSCI as at least moderate (<1.5 standard deviation) deficits in ⩾2 cognitive domains. Multivariable regression analysis was applied to define risk factors for PSCI. Results: We analyzed 329 non-aphasic patients admitted from December 2020 to July 2023 (67.2 ± 14.4 years old, 41.3% female, 13.1 ± 2.7 years of education). Although most patients had mild stroke (median National Institutes of Health Stroke Scale (NIHSS) 24 h = 1.00 (0.00; 3.00); 87.5% with NIHSS ⩽ 5), 69.3% of them presented with PSCI 2.7 ± 2.0 days post-stroke. The most severely and often affected cognitive domains were verbal learning, episodic memory, executive functions, selective attention, and constructive abilities (39.1%–51.2% of patients), whereas spatial neglect was less frequent (18.5%). The risk of PSCI was reduced with more years of education (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23–0.99) and right hemisphere lesions (OR = 0.47, 95% CI = 0.26-0.84), and increased with stroke severity (NIHSS 24 h, OR = 4.19, 95% CI = 2.72-6.45), presence of hyperlipidemia (OR = 1.93, 95% CI = 1.01–3.68), but was not influenced by age. After adjusting for stroke severity and depressive symptoms, acute PSCI was associated with poor functional outcome (modified Rankin Scale > 2, F = 13.695, p < 0.001) and worse global cognition (Montreal Cognitive Assessment (MoCA) score, F = 20.069, p < 0.001) at 3 months post-stroke. Conclusion: Despite modern stroke therapy and many strokes having mild severity, PSCI in the acute stroke phase remains frequent and associated with worse outcome. The most prevalent were learning and memory deficits. Cognitive reserve operationalized as years of education independently protects post-stroke cognition. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited. METHODS: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US‐representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross‐sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression. RESULTS: In weighted models, greater loneliness was associated with microinfarcts, lower episodic and working memory in the absence of AD pathology, lower working memory in the absence of infarcts, a stronger association of infarcts with lower episodic memory, and a stronger association of microinfarcts with lower working and semantic memory. DISCUSSION: Loneliness may relate to AD through multiple pathways involving cerebrovascular pathology and cognitive reserve. Highlights: Loneliness was associated with worse cognition in five domains.Loneliness was associated with the presence of microinfarcts.Loneliness moderated cognition–neuropathology associations.Transportability methods can provide insight into selection bias. [ABSTRACT FROM AUTHOR]

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Introduction: Cognitive frailty and the related concepts of cognitive reserve and imaging-based brain frailty are of increasing interest in older adult care. However, there is uncertainty regarding their importance within a stroke population. We aimed to establish the prevalence of cognitive frailty and reserve in stroke and determine impact on outcomes. Methods: We conducted a systematic review across multidisciplinary electronic databases using validated search syntax. The protocol for this review has been published (PROSPERO, CRD42023433385). We identified studies on cognitive frailty and cognitive reserve, including studies that used related concepts. We extracted data to inform estimates of prevalence and associations with outcomes of physical function, cognition and quality of life, performing meta-analyses where possible. Risk of bias was assessed using Newcastle-Ottawa tools appropriate to study design. Results: Our search returned 12,095 studies, from which 14 papers met our criteria. No studies described cognitive frailty, and rather studies described cognitive reserve and brain frailty. Cognitive reserve was assessed using proxy measures of education, employment, and leisure time. Four studies used the Cognitive Reserve Index Questionnaire (CRIq) with pooled estimate score of 103.25, 95% CI: 96.87–109.65 (indicating moderate cognitive reserve). Cognitive reserve had varying associations with post-stroke outcomes, three studies (n = 7,759 participants) reporting significant negative association with cognitive measures. Brain frailty was assessed using imaging markers. Across four studies (n = 3,086 participants), pooled prevalence of brain frailty was 73.8%, 95% CI: 72.2–75.3. Higher brain frailty was associated with poorer post-stroke outcomes for majority of studies assessed. Seven studies (50%) were scored as low risk of bias. Conclusion: Attempts to synthesise these data were complicated by inconsistency in terminology and heterogeneity in methods. However, our findings suggest that brain frailty is common in stroke and associated with poorer outcomes. The epidemiology of cognitive frailty and reserve is less well described. All these measures may be useful for prognostication in stroke, but there are multiple areas where more research is needed. [ABSTRACT FROM AUTHOR]

AbstractA new model of reserve, the Sensory, Emotional, and Cognitive Reserve (SEC) model, has been recently proposed, but so far this model has not been operationalized in instruments to evaluate the different domains of the reserve. This study introduces the SEC reserve inventory (SECri) along with preliminary data obtained from a study involving 57 adults, aged 35 and older. The SECri assesses the SEC domains using specific proxies: (a) sensory reserve (SR) through sensory acuity and sensory perception proxies; (b) emotional reserve (ER) through life events, resilience, and emotional regulation proxies; and (c) cognitive reserve (CR) through education, occupation, socioeconomic status, bilingualism, leisure activities, and personality traits proxies. Key features of SECri include self- and informant-report forms, fine-grained response scales, and the evaluation of reserve development across the lifespan. Findings on the acceptability, convergent validity between SECri domains and validated tests for the same constructs, internal consistency of each domain, and predictive validity of Montreal Cognitive Assessment scores support further research with this inventory. Future studies should consider determining SECri’s psychometric properties in clinical and subclinical conditions to evaluate its prognostic value in cases of neurocognitive decline. [ABSTRACT FROM AUTHOR]

AbstractObjective: Cognitive reserve (CR) is the brain’s ability to cope with changes related to aging and/or disease. Originally introduced to explain individual differences in the clinical manifestations of dementia, CR has recently emerged as a relevant construct in stroke and traumatic brain injury (TBI). This systematic review aims to investigate whether CR could predict post-stroke and TBI clinical recovery and rehabilitation outcomes, and how different variables used to estimate CR (i.e., proxies) are related to the prognosis and effectiveness of rehabilitation in these clinical populations. Method: A search was made in Pubmed, Embase, and PsycInfo for articles published until 12 January 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol guidelines. Results: 31 studies were included after completing all screening stages. Overall, results show that a higher CR was associated with a better prognosis and a more effective rehabilitation in most of the clinical aspects considered: cognitive functioning, functional, occupational, and socio-emotional abilities, as well as psychiatric and neurological scales. Conclusions: A higher CR seems to be associated with a more favorable prognosis and a better rehabilitation outcome after stroke and TBI. Results suggest that CR should be taken into account in clinical practice to make more accurate predictions about recovery and effectiveness of rehabilitation. However, some inconsistencies suggest the need for further investigations, possibly using multiple proxies for CR. [ABSTRACT FROM AUTHOR]

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance. Aims: The objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P). Methods: 68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables. Results: Simple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (β > 0.3, p <.001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale. Conclusion: As CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater. [ABSTRACT FROM AUTHOR]

Soft skills are key factors for success in multiple contexts of daily life, as well as for life satisfaction, but little is known about their role in late adulthood and older age. In this study, we aimed to investigate the relationships of soft skills, as defined by the World Economic Forum, with two indicators of successful/healthy aging: life satisfaction and cognitive reserve. A sample of 435 adults aged 50 and over completed self-reported measures of soft skills, life satisfaction, and cognitive reserve. As control, fluid (reasoning) and crystalized (vocabulary) intelligence were assessed too, along with socio-demographic characteristics. A series of regression analyses showed that soft skills were positively related to both life satisfaction and, to a lower extent, cognitive reserve, above and beyond gender, age, and both fluid and crystallized intelligence. Interestingly, these associations were independent from participants' age. Overall, these results highlight the importance of considering soft skills also over the middle-late adult life course, due to the potential role of these individual qualities in supporting an individual's well-being and an active and engaged lifestyle, with implications for the promotion of a healthy aging. [ABSTRACT FROM AUTHOR]

Objective: The present study examined the cognitive reserve (CR) theory at late stages of Alzheimer's disease (AD). The objective is to replicate previous studies and examine the complex role of education and family size as indicators of CR. Participants and methods: This is a retrospective study included 642 patients diagnosed with AD after age 65, categorized into low education (LE, ≤ 8 years, n = 141) and medium-high education (MHE, ≥ 9 years, n = 442) groups. Participants were followed up longitudinally using the Mini Mental State Examination. Results: Higher education in the MHE group, but not in the LE group, correlated with delayed diagnosis. In both groups, higher education correlated with accelerated cognitive decline. In the MHE group, country of origin was associated with cognitive decline, while in the LE group, it was linked to family size. Conclusions: This study shows that in patients with MHE but not in LE, higher education resulted in delayed diagnosis. Conversely, in cases of LE, this measure may not fully reflect CR and abilities. Additionally, higher education was associated with faster deterioration, a finding that has not been replicated often in the literature. The study illustrates the complex impact of CR proxies on age of diagnosis and cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives Tests of physical function are often thought to measure functioning that is (1) musculoskeletal, and (2) newly declining in adult life. In contrast, this study aimed to: (1) add to evidence that physical-function tests also measure brain function, and (2) test the novel hypothesis that adult physical function is associated with brain function beginning in early childhood. We investigated early childhood brain function and midlife physical function in the Dunedin Study, a 5-decade longitudinal birth cohort (n  = 1,037). Methods Brain function was measured at age 3 using 5 measures which formed a reliable composite (neurological examination, cognitive and motor tests, and temperament ratings). Physical function was measured at age 45 using 5 measures which formed a reliable composite (gait speed, step-in-place, chair stands, balance, and grip strength). Results Children with worse age-3 brain function had worse midlife physical function as measured by the age-45 composite, even after controlling for childhood socioeconomic status (β: 0.23; 95% CI: 0.16 to 0.30; p  < .001). Worse age-3 brain function significantly predicted slower gait speed, fewer steps-in-place and chair-stands, worse balance, and weaker grip strength. Discussion Children with poorer brain function were more likely to have poorer physical-function scores as adults. In addition to indicating recent musculoskeletal decline, physical-function tests may also provide indications of lifelong, integrated brain–body health. By reconceptualizing the meaning of physical-function scores, clinicians can orient the use of physical-function tests in a more holistic approach to health care. [ABSTRACT FROM AUTHOR]

A higher level of education was correlated with less severe motor impairment in Parkinson's Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study's findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD. [ABSTRACT FROM AUTHOR]

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition – not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life. • Cognitive reserve permits people to cope with brain pathology and delay dementia. • Cognitive reserve can be accrued from cognitive, physical, and social activities. • Cognitive reserve slowed age-related cognitive decline – not gait speed decline. • Results were consistent across cognitive, physical, and social reserve proxies. [ABSTRACT FROM AUTHOR]

Abstract Background Females have a higher age-adjusted incidence of Alzheimer’s Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building cognitive reserve, particularly through stimulating avocational activities and occupational attainment presents a crucial, underexplored, dementia prevention approach for mid-life. It is currently unknown, however, whether modifiable lifestyle factors can protect against AD processes, from mid-life, differentially for females and males who carry inherited risk for late-life dementia. To address this gap, this study investigated the impact of biological sex and APOE4 carrier status on the relationship between stimulating activities, occupational attainment, and cognition in mid-life. Methods We leveraged the PREVENT–Dementia program, the world’s largest study investigating the origins and early diagnosis of dementia in mid-life at-risk individuals (N = 700; 40–59 years). Cognitive performance was measured using the Cognito Battery and the Visual Short Term Memory Binding task. Mid-life specific reserve contributors were assessed via the Lifetime of Experiences Questionnaire. Results Females had significantly better episodic and relational memory (p

Background Cognitive dysfunction is frequently seen in multiple sclerosis (MS). However, there are conflicting findings regarding the factors it is associated with.

Background and objectivesThe existing literature highlights the importance of reading books in middle-to-older adulthood for cognitive functioning; very few studies, however, have examined the importance of childhood cognitive resources for cognitive outcomes later in life.Research design and methodsUsing data from 11 countries included in the Survey of Health, Ageing, and Retirement in Europe (SHARE) data set (N = 32,783), multistate survival models (MSMs) were fit to examine the importance of access to reading material in childhood on transitions through cognitive status categories (no cognitive impairment and impaired cognitive functioning) and death. Additionally, using the transition probabilities estimated by the MSMs, we estimated the remaining years of life without cognitive impairment and total longevity. All models were fit individually in each country, as well as within the pooled SHARE sample.ResultsAdjusting for age, sex, education, and childhood socioeconomic status, the overall pooled estimate indicated that access to more books at age 10 was associated with a decreased risk of developing cognitive impairment (adjusted hazard ratio = 0.79, confidence interval: 0.76-0.82). Access to childhood books was not associated with risk of transitioning from normal cognitive functioning to death, or from cognitive impairment to death. Total longevity was similar between participants reporting high (+1 standard deviation [SD]) and low (-1 SD) number of books in the childhood home; however, individuals with more access to childhood books lived a greater proportion of this time without cognitive impairment.Discussion and implicationsFindings suggest that access to cognitive resources in childhood is protective for cognitive aging processes in older adulthood.

IntroductionHigher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations.MethodsIn a diverse cohort (n = 1536), linear mixed-effects models estimated associations between main lifetime occupational complexity and domain-specific cognitive decline (z-standardized). Occupational complexity with data, people, and things were classified using the Dictionary of Occupational Titles.ResultsFor occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (β = 0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (β = 0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (β = 0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (β = 0.29; 95% CI 0.18-0.40), verbal episodic memory (β = 0.12; 95% CI 0.00-0.24), and semantic memory (β = 0.23; 95% CI 0.12-0.34).DiscussionIn a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts.HighlightFew studies have examined associations of occupational complexity with cognition in diverse populations. Racial and ethnic minorities are disproportionately exposed to lower occupational complexity. Occupational complexity with data and people are associated with better cognition.

BACKGROUND: The effect of years of education on the maintenance of healthy cognitive functioning may differ by race and ethnicity given historical and ongoing inequities in educational quality. METHODS: We examined 20,311 Black, Latinx, and White adults aged 51-100 from the Health and Retirement Study (2008-2016). Telephone Interview for Cognitive Status-27 data was used to measure cognitive functioning. Generalized additive mixed models were stratified by race and ethnicity and educational attainment (≥12 vs.

Aging is often accompanied by changes in brain structure and executive functions, particularly in tasks involving cognitive flexibility, such as task-switching. However, substantial individual differences in the degree of cognitive impairment indicate that some individuals can cope with brain changes more effectively than others, suggesting higher cognitive reserve (CR). This study identified a neural basis for CR by examining the longitudinal relationship between task-related brain activation, structural brain changes, and changes in cognitive performance during an executive task-switching paradigm including single and dual conditions. Fifty-two older individuals were assessed at baseline and followed up after five years. Structural brain changes related to task-switching performance were analyzed using elastic net regression. Task-related functional brain activation was measured using ordinal trends canonical variate analysis (OrT CVA), capturing patterns of activation increasing from single to dual conditions. A differential task-related expression score (dOrT) was calculated as the difference in pattern expression scores between single and dual conditions at baseline. A linear regression model tested whether dOrT moderated the impact of brain changes on changes in switch cost over five years. Results showed a significant interaction between changes in brain structure and dOrT activation on switch cost change, indicating a moderation effect of task-related activation. Higher dOrT buffered the impact of brain structural decline on switch costs, enabling older adults to better cope with age-related brain structural changes and preserve cognitive flexibility. These findings suggest that these task-related activation patterns represent a neural basis for CR. • Longitudinal study on task activation as neural basis of cognitive reserve in aging. • Functional brain activation moderates effects of structural decline on cognition. • Higher differential activation lessens brain change effects on set-switching ability. [ABSTRACT FROM AUTHOR]

Purpose: Two-sample Mendelian randomization methods were used to explore the causal effects of cognitive reserve proxies, such as educational attainment, occupational attainment, and physical activity (PA), on biological (leukocyte telomere length), phenotypic (sarcopenia-related features), and functional (frailty index and cognitive performance) aging levels. Results: Educational attainment had a potential protective effect on the telomere length (β = 0.10, 95% CI: 0.08–0.11), sarcopenia-related features (β = 0.04–0.24, 95% CI: 0.02–0.27), frailty risk (β = −0.31, 95% CI: −0.33 to −0.28), cognitive performance (β = 0.77, 95% CI: 0.75–0.80). Occupational attainment was causally related with sarcopenia-related features (β = 0.07–0.10, 95% CI: 0.05–0.14), and cognitive performance (β = 0.30, 95% CI: 0.24–0.36). Device-measured PA was potentially associated with one sarcopenia-related feature (β = 0.14, 95% CI: 0.03–0.25). Conclusions: Our findings support the potential causality of educational attainment on biological, phenotypic, and functional aging outcomes, of occupational attainment on phenotypic and functional aging-related outcomes, and of PA on phenotypic aging-related outcomes. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) are associated with later cognitive decline. However, the mechanisms underlying the effects of different types of ACEs are unclear. This study examined how ACEs impact cognitive function, specifically deprivation-related ACEs (DrACEs) and threat-related ACEs (TrACEs). Additionally, we explored the potential role of cognitive reserve (CR) and depression in these relationships. Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2020. CR, depressive symptoms and cognitive function measures were collected from 2020. ACEs were assessed at the 2014 Life Course Survey. The main analyses included 7113 participants aged 45 years or older. To explore potential associations, linear regression and SPSS Macro PROCESS were employed. Among middle-aged and older adults, only exposure to DrACEs was associated with cognitive function ((β = −0.101 [95% CI : −0.150, −0.052]) for DrACEs = 1; (β = −0.250 [95% CI : −0.333, −0.167]) for DrACEs ≥ 2). The indirect effects mediated by CR and depressive symptoms were statistically significant. The use of retrospective self-reported data for ACEs may introduce recall bias. Chinese middle-aged and older adults who have experienced DrACEs exhibit poorer cognitive function, while the association between TrACEs and cognitive function was not significant. And the impact of DrACEs on cognitive function was mediated by CR and depressive symptoms. Further research is necessary to validate our findings, establish causal links, and uncover the underlying mechanisms involved. • Deprivation-related adverse childhood experiences led to lower cognitive function in later life. • Threat-related experiences had no significant impact on cognitive function in later life. • The impact of deprivation was mediated by cognitive reserve and depressive symptoms. [ABSTRACT FROM AUTHOR]

Abstract Objectives To identify the prevalence and associated factors of cognitive dysfunction, 1 year after ICU discharge, among adult patients, and it´s relation with quality of life. Methods Multicenter, prospective cohort study including ICUs of 10 tertiary hospitals in Brazil, between May 2014 and December 2018. The patients included were 452 adult ICU survivors (median age 60; 47.6% women) with an ICU stay greater than 72 h. Results At 12 months after ICU discharge, a Montreal Cognitive Assessment (tMOCA) telephone score of less than 12 was defined as cognitive dysfunction. At 12 months, of the 452 ICU survivors who completed the cognitive evaluation 216 (47.8%) had cognitive dysfunction. In multivariable analyses, the factors associated with long-term (1-year) cognitive dysfunction were older age (Prevalence Ratio–PR = 1.44, P

Abstract Background Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. Methods Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. Results At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p

Objectives. Among people over the age of 65, the prevalence of olfactory disorders can reach nearly 14%. The buildup of beta-amyloid plaques and tau neurofibrillary tangles in neurons in the hippocampus and entorhinal cortex causes olfactory dysfunction, a decline in memory and learning processes, and, eventually, Alzheimer's disease. According to current research, people aged 57 to 85 who have hyposmia are twice as likely to develop dementia within five years as people of the same age who do not have hyposmia. Anosmia is one of the most common COVID-19 symptoms. Methodology. An 81-year-old female patient is referred to the psychiatry clinic by her family physician after presenting with a two-year history of panic attacks, anxiety, and anosmia following the SARS-CoV-2 infection. At the first visit, the patient was examined neurologically, psychiatrically, and neurocognitively with the Mini-Mental State Examination-2 and Cognitive Reserve Questionnaire. The patient was recommended for laboratory tests, magnetic resonance imaging scan, and a complex neuropsychological evaluation. Results. The score on the Mini-Mental State Examination-2 (standard version) was 28/30, with fluent language, high cognitive reserve (score of 168), normal muscle tone and strength, and no evidence of cerebellar dysfunction or balance impairment with a normal gait. The extensive neuropsychological evaluation scores were: Mini-Mental State Examination-2 (extended version) 42/90; three words from 25 retained from short story recall; Montreal Cognitive Assessment 20/30; poor verbal fluency (patient was able to produce only six animal names and one word that starts with the letter F in one minute); and impaired visuospatial and executive abilities. Brain imaging results reveal moderate cortical atrophy, cerebral microangiopathy modifications with leukoaraiosis, and cerebral lacunarism. Conclusions. Olfactory impairment is a possible sign of prodromal dementia. Infection with the SARS-Cov-2 virus has worsened cognitive decline in patients with Alzheimer's disease.

Abstract Background Mild cognitive impairment (MCI) describes an aging profile characterized by a cognitive decline that is worse than expected in normal aging but less pervasive and critical than full-blown dementia. In the absence of an effective treatment strategy, it is important to identify factors that can protect against progression to dementia. In this field, it is hypothesized that one aspect that may be a protective factor against the neurotypical outcome of dementia is cognitive reserve (CR). Cognitive reserve is the ability to maintain cognitive functionality despite accumulating brain pathology. Objectives The present study aimed to identify and analyze the differences in CR between healthy adults and patients with MCI. Specifically, it is hypothesized that (i) healthy older adult people have higher CR than older adult people diagnosed with MCI, and (II) CR could predict the classification of subjects into people with or without MCI. Methods Two hundred forty-three adults (mean age = 60.4, SD = 7.4) participated in the present study and were classified into three groups based on Petersen’s MCI criteria: healthy controls (HC), amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The Cognitive Reserve Index questionnaire (CRIq) was administered to assess the level of CR, Findings Results showed that HC had significantly higher CR scores than participants diagnosed with aMCI and naMCI. Moreover, a binomial logistic regression suggested that low CR was a significant risk factor for the MCI diagnosis. Conclusions The clinical picture that emerged from the results showed that lower CR could be considered a characteristic of pathological aging, such as MCI.Public significance statement, Since the brain attempts to cope with life-related changes or pathologies, it is fundamental for both clinicians and researchers to investigate further the factors that contribute to brain resilience. As an indirect expression of brain reserve, cognitive reserve may be both a marker and a predictor of adaptive aging.

Abstract Human aging is a physiological, progressive, heterogeneous global process that causes a decline of all body systems, functions, and organs. Throughout this process, cognitive function suffers an incremental decline with broad interindividual variability. The first objective of this study was to examine the differences in the performance on the MoCA test (v. 7.3) per gender and the relationship between the performance and the variables age, years of schooling, and depressive symptoms .The second objective was to identify factors that may influence the global performance on the MoCA test (v. 7.3) and of the domains orientation, language, memory, attention/calculation, visuospatial and executive function, abstraction, and identification. A cross-sectional study was carried out in which five hundred seventy-three (573) cognitively healthy adults ≥ 50 years old were included in the study. A sociodemographic questionnaire, the GDS-15 questionnaire to assess depression symptoms and the Spanish version of the MoCA Test (v 7.3) were administered. The evaluations were carried out between the months of January and June 2022. Differences in the MoCA test performance per gender was assessed with Student’s t-test for independent samples. The bivariate Pearson correlation was applied to examine the relationship between total scoring of the MoCA test performance and the variables age, years of schooling, and depressive symptoms. Different linear multiple regression analyses were performed to determine variables that could influence the MoCA test performance. We found gender-related MoCA Test performance differences. An association between age, years of schooling, and severity of depressive symptoms was observed. Age, years of schooling, and severity of depressive symptoms influence the MoCA Test performance, while gender does not.

Background and objectives: Cognitive reserve (CR) is a property of the brain that allows for better-than-expected cognitive performance relative to the degree of brain change over the course of life. However, neurophysiological markers of CR remain under-investigated. Electroencephalography (EEG) features may function as suitable neurophysiological markers of CR. To assess this, we investigated whether the dorsal attention network (DAN) and ventral attention network (VAN) activities, as measured during resting-state EEG, moderate the relationship between hippocampal volume and episodic memory. Methods: Participants were recruited as part of the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Hippocampal volume was determined using magnetic MRI, and episodic memory was measured using word lists. After testing the effect of hippocampal volume on memory performance using multiple regression analysis, we evaluated the interactions between hippocampal volume and DAN and VAN network activities. We further used the Johnson-Neyman technique to quantify the moderating effects of DAN and VAN network activities on the relationship between hippocampal volume and word list memory, as well as to identify specific ranges of DAN and VAN network activity with significant hippocampal-memory association. Results: A total of 449 participants were included in this study. Our analysis revealed significant moderation of DAN with a slope of β = -0.00012 (95% CI: -0.00024; -0.00001, p = 0.040), and VAN with a slope of β = 0.00014 (95% CI: 0.00001; 0.00026, p = 0.031). Further, we found that a larger hippocampal volume was associated with improved memory performance, and that this association became stronger as the DAN activity decreased until a limit of DAN activity of 944.9, after which the hippocampal volume was no longer significantly related to word-list memory performance. For the VAN, we found that a higher hippocampal volume was more strongly associated with better memory performance when VAN activity was higher. However, when VAN activity extended beyond -914.6, the hippocampal volume was no longer significantly associated with word-list memory. Discussion: Our results suggest that attentional networks help to maintain memory performance in the face of age-related structural decline, meeting the criteria for the neural implementation of cognitive reserve. [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging, manifesting as superior performance on cognitive tasks compared to monolingual counterparts. Yet, the cognitive impacts of acquiring a new language in older adulthood remain unexplored. In this study, we assessed both behavioral and fMRI responses during a Stroop task in older adults, preand post language-learning intervention. Methods: A group of 41 participants (age:60-80) from a predominantly monolingual environment underwent a four-month online language course, selecting a new language of their preference. This intervention mandated engagement for 90 minutes a day, five days a week. Daily tracking was employed to monitor progress and retention. All participants completed a color-word Stroop task inside the scanner before and after the language instruction period. Results: We found that performance on the Stroop task, as evidenced by accuracy and reaction time, improved following the language learning intervention. With the neuroimaging data, we observed significant differences in activity between congruent and incongruent trials in key regions in the prefrontal and parietal cortex. These results are consistent with previous reports using the Stroop paradigm. We also found that the amount of time participants spent with the language learning program was related to differential activity in these brain areas. Specifically, we found that people who spent more time with the language learning program showed a greater increase in differential activity between congruent and incongruent trials after the intervention relative to before. Discussion: Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations. We propose that with sufficient engagement, language learning can enhance specific domains of cognition such as the executive functions. These results extend the understanding of cognitive reserve and its augmentation through targeted interventions, setting a foundation for future investigations. [ABSTRACT FROM AUTHOR]

Most researchers have assessed cognitive functions in post-COVID-19 patients by means of screening tools and found cognitive sequelae in addition to anxiety, stress, depression, and a reduced quality of life (QoL). This study was aimed at investigating cognitive and psychological sequelae in patients admitted to the intensive care unit (ICU) six months (t6) and one year (t12) after discharge from the hospital, the impact of critical illness on well-being and QoL, and the protective role of cognitive reserve (CR). Twenty-three ICU patients underwent an extensive neuropsychological test battery at t6 and t12; a healthy control group underwent the same evaluation. Patient scores were compared with control scores: patients reported significantly lower scores in visual–spatial functions, both at t6 (U = 122; p = 0.033) and at t12 (U = 70; p = 0.003), and higher levels of anxiety (U = 126; p = 0.043) and depression (U = 97; p = 0.005) at t6; the levels of anxiety decreased at t12, while only depression symptoms persisted (U = 99.5; p = 0.025). Regarding the QoL, patients obtained lower scores in the physical component of QoL, both at t6 (U = 72; p = 0.008) and at t12 (U = 56.5; p = 0.005). Few and moderate correlations emerged between isolated cognitive functions and CR and the length of hospital stay. The results suggest a prevalent visual–spatial involvement, the medium- and long-term persistence of psychological sequelae, and a reduced QoL in ICU patients. [ABSTRACT FROM AUTHOR]

AbstractObjective: The current study examined the longitudinal relationship between cognitive reserve (CR), depression, and executive function (EF) in a cohort of older adults. Methods: 416 participants were selected from the Wisconsin Registry for Alzheimer’s Prevention. They were native English speakers, aged ≥50+, and cognitively unimpaired at baseline, with no history of neurological or other psychiatric disorders aside from depression. Depression was assessed with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). A composite score, based on the premorbid IQ (WRAT-3 Reading subtest) and years of education was used to estimate CR. Another composite score from four cognitive tests was used to estimate EF. A moderation analysis was performed to evaluate the effects of CR and Depression on EF at follow-up after controlling for age, gender, and APOE risk score. Moreover, a multinomial logistic regression was used to predict conversion to Mild Cognitive Impairment (MCI) from the healthy baseline. Results: The negative relationship between depression and EF was stronger in individuals with higher CR levels, suggesting a possible floor effect at lower CR levels. In the multinomial regression, the interaction between CR and depression predicted conversion to MCI status, indicating that lower CR paired with more severe depression at baseline was associated with a higher risk of subsequent impairment. Conclusions: This study sheds light on the intricate relationship between depression and EF over time, suggesting that the association may be influenced by varying levels of CR. Further studies may replicate these findings in clinical populations. [ABSTRACT FROM AUTHOR]

Asymptomatic Alzheimer's disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer's disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aβ, preserving brain health, and slowing AD pathology progression. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the interaction of cognitive reserve (CR) and state anxiety in adrenocortical and electrodermal responses. Thirty-nine healthy, middle-aged men completed the State–Trait Anxiety Inventory and Escala de Reserva Cognitiva (Cognitive Reserve Scale). Following this, they performed a cognitively demanding task adapted from the Trier Social Stress Test. Electrical skin conductance level and cortisol concentrations were recorded during the task. These measures were used as indicators of stress response. Our results seem to indicate that CR has a protective effect against cortisol responses in stressful situations. This effect was observed in participants who showed high CR and high state anxiety. At the same time, CR showed a positive correlation with "recovery to baseline conductance level" after the occurrence of stressful events. As a whole, these results suggest that having high CR could protect against the development of allostatic load. The regulatory system of physiological and endocrine activity would be more efficient in individuals with high scores in CR, thus avoiding the development of allostatic load. [ABSTRACT FROM AUTHOR]

Emotional intelligence (EI) and neurocognition (NC) impairments are common in first-episode psychosis (FEP), yet their evolution over time remains unclear. This study identified patient profiles in EI and NC performance in FEP. 98 adult FEP patients and 128 healthy controls (HCs) were tested on clinical, functional, EI, and NC variables at baseline and two-year follow-up (FUP). A repeated-measures ANOVA compared the effects of group (patients and HCs) and time on EI. Significant EI improvements were observed in both groups. Four groups were created based on NC and EI performance at baseline and FUP in patients: impairment in NC and EI, impairment in NC only, impairment in EI only, and no impairment. At FUP, patients impaired in NC and EI showed less cognitive reserve (CR), greater negative and positive symptoms, and poorer functional outcomes. At FUP, three group trajectories were identified: (I) maintain dual impairment (II) maintain no impairment or improve, (III) maintain sole impairment or worsen. The maintain dual impairment group had the lowest levels of CR. EI and NC impairments progress differently in FEP. Greater CR may protect against comorbid EI/NC impairment. Identifying these patient characteristics could contribute to the development of personalised interventions. [ABSTRACT FROM AUTHOR]

Background/Objectives: High cognitive reserve (CR) has been shown to have beneficial effects on global cognition, cognitive decline, and risk of dementia in Parkinson's disease (PD). We evaluated the influence of CR on the long-term cognitive outcomes of patients with PD who underwent subthalamic nucleus deep brain stimulation (STN-DBS). Methods: Twenty-five patients with PD underwent neuropsychological screening using the Montreal Cognitive Assessment (MoCA) at baseline, 1 year, and 5 years after bilateral STN-DBS. CR was assessed using the Cognitive Reserve Index questionnaire. According to CR score, patients were assigned to two different groups (LowCR group ≤ 130, HighCR group > 130). Results: Our data showed that patients in the HighCR group obtained a better performance with the MoCA total score at long-term follow-up compared to those in the LowCR group ([mean ± SE] LowCR group: 21.4 ± 1.2 vs. HighCR group: 24.5 ± 1.3, p = 0.05). The cognitive profile of the HighCR group remained unchanged over time. Conversely, the LowCR group had worse global cognition 5 years after surgery (T0: 25.3 ± 0.6 vs. T2: 21.4 ± 1.2, p = 0.02). Cognitive decline was not associated with mood, demographics, or clinical variables. Conclusions: These preliminary findings suggest that higher CR may be protective in PD cognition after STN-DBS. Specifically, a high CR may help cope with long-term decline in the context of surgical treatment. Quantifying a patient's CR could lead to more personalized medical care, tailoring postoperative support and monitoring for those at higher risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to explore the suitability of the vocabulary knowledge (VOC) test as an accurate and reliable proxy of cognitive reserve (CR) by evaluating its psychometric properties and discrimination accuracy compared with other CR measures in multiple sclerosis (MS). Methods: Sixty-eight consecutive people with multiple sclerosis (pwMS), followed at our MS outpatient clinic, completed a clinical evaluation and neuropsychological assessment including: VOC, Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), Beck Depression Inventory-II, and State-Trait Anxiety Inventory. Reliability, convergent and divergent validity, and discrimination accuracy of the VOC were assessed using educational level as reference standard. The possible effects of sociodemographic and clinical factors on VOC and their role in predicting global cognitive status were also explored. Results: VOC demonstrated good internal consistency (Cronbach's α = 0.894) and adequate construct validity. It showed an acceptable level of discrimination between pwMS with high and low CR, comparable to the CRIq score. Education strongly affected VOC scores, which in turn were independent of MS features. VOC emerged as an independent predictor of global cognitive status together with MS-related disability. Conclusion: We demonstrated the validity of VOC as a reliable CR measure in pwMS. Thus, CR may also be estimated using fixed objective measures, independent of brain pathology and clinical features. Early CR estimation may help clinicians identify pwMS at a higher risk of cognitive decline and plan strict neuropsychological monitoring and cognitive interventions. [ABSTRACT FROM AUTHOR]

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact of specific, empirically derived occupational skills and requirements on cognitive and motor functioning in ALS. Individuals with ALS (n = 150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) measured cognition, and the Penn Upper Motor Neuron (PUMNS) and ALS Functional Rating Scales (ALSFRS-R) measured motor symptoms. We derived 17 factors representing distinct occupational skills and requirements from the Occupational Information Network (O*NET), which were related to cognitive and motor scores using multiple linear regression. Occupational roles involving greater reasoning ability (β = 2.12, p <.05), social ability (β = 1.73, p <.05), analytic skills, (β = 3.12, p <.01) and humanities knowledge (β = 1.83, p<.01) were associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=−2.57, p <.01) and technical skills (β=−2.16, p<.01) were associated with lower ECAS scores. Jobs requiring more precision skills (β = 1.91, p <.05) were associated with greater motor dysfunction on the PUMNS. Occupational histories involving more cognitively complex skills and activities were related to preserved cognitive functioning in ALS consistent with the cognitive reserve hypothesis, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. Jobs involving more repetitive movements were associated with worse motor functioning, possibly due to overuse. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS. [ABSTRACT FROM AUTHOR]