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Introduction: Disproportionately Enlarged Subarachnoid space Hydrocephalus (DESH) is considered as an important imaging feature of idiopathic normal pressure hydrocephalus (iNPH)., Method: Subjects aged 60 and over in a memory clinic and a community-based cohort were assessed for the presence of ventriculomegaly, Sylvian dilatation, and high convexity tightness by neuroimaging, and a clinical triad of iNPH symptoms, i.e. cognitive, gait and urinary symptoms., Results: In the memory clinic-based study (548 subjects), the prevalence of DESH was 1.1% and increased with age. The clinical triad was significantly more frequent in subjects with DESH (50%) compared to those with normal images (none), Sylvian dilatation (7%), and ventriculomegaly (12%). Gait disturbance was also significantly more frequent in DESH (83%) compared to those with normal images (2%), Sylvian dilatation (14%), and ventriculomegaly (26%). In the community-based cohort (946 subjects), the prevalence of DESH was 1.0% and increased with age. The clinical triad (11%) was significantly more common in subjects with DESH compared to those with normal images (none), Sylvian dilatation (2%), and ventriculomegaly (7%). Gait disturbance was also significantly more common in DESH (33%) compared to those with normal images (1%), Sylvian dilatation (4%), and ventriculomegaly (10%)., Conclusion: The reported prevalence of DESH was approximately 1%, and increased with age. DESH and high convexity tightness were specifically associated with the clinical triad of iNPH. Of the triad, gait disturbance was associated to DESH and high convexity tightness., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intracranial stenosis (ICS) and brain amyloid-beta (Aβ) have been associated with cognition and dementia. We aimed to investigate the association between ICS and brain Aβ and their independent and joint associations with cognition.Methods: We conducted a cross-sectional study of 185 patients recruited from a memory clinic. ICS was measured on 3-dimensional time-of-flight magnetic resonance angiography and defined as stenosis ≥50%. Brain Aβ was measured with [ 11 C] Pittsburgh compound B-positron emission tomography imaging. Cognition was assessed with a locally validated neuropsychological battery.Results: A total of 17 (9.2%) patients had ICS, and the mean standardized uptake value ratio was 1.4 (±0.4 SD). ICS was not significantly associated with brain Aβ deposition. ICS was significantly associated with worse global cognition (β: -1.26, 95% CI: -2.25; -0.28, P =0.013), executive function (β: -1.04, 95% CI: -1.86; -0.22, P =0.015) and visuospatial function (β: -1.29, 95% CI: -2.30; -0.27, P =0.015). Moreover, in ICS patients without dementia (n=8), the presence of Aβ was associated with worse performance on visuomotor speed.Conclusions: ICS was significantly associated with worse cognition and showed interaction with brain Aβ such that patients with both pathologies performed worse on visuomotor speed specifically in those without dementia. Further studies may clarify if ICS and brain Aβ deposition indeed have a synergistic association with cognition. [ABSTRACT FROM AUTHOR]

Background: The underlying cause of cognitive decline in individuals who are positive for biomarkers of neurodegeneration (N) but negative for biomarkers of amyloid‐beta (A), designated as Suspected non‐Alzheimer's pathophysiology (SNAP), remains unclear. We evaluate whether cerebrovascular disease (CeVD) is more prevalent in those with SNAP compared to A−N− and A+N+ individuals and whether CeVD is associated with cognitive decline over time in SNAP patients. Methods: A total of 216 individuals from a prospective memory clinic cohort (mean [SD] age, 72.7 [7.3] years, 100 women [56.5%]) were included and were diagnosed as no cognitive impairment (NCI), cognitive impairment no dementia (CIND), Alzheimer's dementia (AD) or vascular dementia (VaD). All individuals underwent clinical evaluation and neuropsychological assessment annually for up to 5 years. Carbon 11‐labeled Pittsburgh Compound B ([11C]‐PiB) or [18F]‐flutafuranol‐positron emission spectrometry imaging was performed to ascertain amyloid‐beta status. Magnetic resonance imaging was performed to assess neurodegeneration as measured by medial temporal atrophy ≥2, as well as significant CeVD (sCeVD) burden, defined by cortical infarct count ≥1, Fazekas score ≥2, lacune count ≥2 or cerebral microbleed count ≥2. Results: Of the 216 individuals, 50 (23.1%) A−N+ were (SNAP), 93 (43.1%) A−N−, 36 (16.7%) A+N− and 37 (17.1%) A+N+. A+N+ individuals were significantly older, while A+N+ and SNAP individuals were more likely to have dementia. The SNAP group had a higher prevalence of sCeVD (90.0%) compared to A−N−. Moreover, SNAP individuals with sCeVD had significantly steeper decline in global cognition compared to A−N− over 5 years (p = 0.042). Conclusions: These findings suggest that CeVD is a contributing factor to cognitive decline in SNAP. Therefore, SNAP individuals should be carefully assessed and treated for CeVD. [ABSTRACT FROM AUTHOR]

Background: P-wave terminal force in lead V1 (PTFV1) on electrocardiography has been associated with atrial fibrillation and ischemic stroke.Objective: To investigate whether PTFV1 is associated with cerebral small vessel disease (CSVD) markers and etiological subtypes of cognitive impairment and dementia.Methods: Participants were recruited from ongoing memory clinic study between August 2010 to January 2019. All participants underwent physical and medical evaluation along with an electrocardiography and 3 T brain magnetic resonance imaging. Participants were classified as no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, and dementia subtypes (Alzheimer's disease and vascular dementia). Elevated PTFV1 was defined as > 4,000μV×ms and measured manually on ECG.Results: Of 408 participants, 78 (19.1%) had elevated PTFV1 (37 women [47%]; mean [SD] age, 73.8 [7.2] years). The participants with elevated PTFV1 had higher burden of lacunes, cerebral microbleeds (CMB), and cortical microinfarcts. As for the CMB location, persons with strictly deep CMB and mixed CMB had significantly higher PTFV1 than those with no CMB (p = 0.005, p = 0.007). Regardless of adjustment for cardiovascular risk factors and/or heart diseases, elevated PTFV1 was significantly associated with presence of CMB (odds ratio, 2.26; 95% CI,1.33-3.91).Conclusion: Elevated PTFV1 was associated with CSVD, especially deep CMB. PTFV1 in vascular dementia was also higher compared to Alzheimer's disease. Thus, PTFV1 might be a potential surrogate marker of brain-heart connection and vascular brain damage. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular disease (CeVD) is an underlying cause of cognitive impairment and dementia. Hypertension is a known risk factor of CeVD, but the effects of mean of visit-to-visit blood pressure (BP) on incident CeVD and functional-cognitive decline remains unclear.Objective: To determine the association between mean of visit-to-visit BP with the incidence and progression of CeVD [white matter hyperintensities (WMH), infarcts (cortical infarcts and lacunes), cerebral microbleeds (CMBs), intracranial stenosis, and hippocampal volume] as well as functional-cognitive decline over 2 years of follow-up.Methods: 373 patients from a memory-clinic underwent BP measurements at baseline, year 1, and year 2. The mean of visit-to-visit systolic BP, diastolic BP, pulse pressure, and mean arterial pressure were calculated. Baseline and year 2 MRI scans were graded for WMH, infarcts, CMBs, intracranial stenosis, and hippocampal volume. Functional-cognitive decline was assessed using locally validated protocol. Logistic and linear regression models with odds ratios, mean difference, and 95%confidence interval were constructed to analyze associations of visit-to-visit BP on CeVD incidence and progression as well as functional-cognitive decline.Results: Higher mean of visit-to-visit diastolic BP was associated with WMH progression. Higher tertiles of diastolic BP was associated with WMH progression and incident CMBs. There was no association between mean of visit-to-visit BP measures with incident cerebral infarcts, intracranial stenosis, change in hippocampal volume, and functional-cognitive decline.Conclusion: These findings suggest the possibility of hypertension-related vascular brain damage. Careful monitoring and management of BP in elderly patients is essential to reduce the incidence and progression of CeVD. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracranial stenosis (ICS) is a risk factor for cognitive impairment and dementia in cross‐sectional studies. However, data examining the effect of ICS on cognitive decline are limited. We investigated the effect of ICS on cognition over a period of 3 years in a memory clinic cohort. Methods: Patients were recruited from the National University Hospital in Singapore. Data were collected using a standardised questionnaire, physical examination, and 3‐T magnetic resonance imaging (MRI) at baseline. ICS was defined as arterial narrowing that exceeded 50% of the luminal diameter in any intracranial vessel. Cognition was measured at baseline and annually for 3 years using the Mini‐Mental State Examination, the Montreal Cognitive Assessment, and a detailed neuropsychological test battery. The association between ICS and cognitive decline was analysed using generalised estimating equations. Results: A total of 364 patients were included in the analysis. The mean (±SD) age was 71.9 (±8.0) years, and 164 (45.1%) patients were male. A total of 66 (18.1%) patients had ICS. ICS was associated with worse executive function (β = −0.37, 95% confidence interval = −0.68 to −0.05, p = 0.022) and modified the effect of follow‐up time on memory (p = 0.005) and visuomotor speed (p = 0.047). These results remained significant after controlling for demographics, overall diagnosis, cardiovascular risk factors, and MRI markers of cerebrovascular disease. Conclusions: Intracranial stenosis was independently associated with worse executive function across all time points, and cognitive decline in memory and visuomotor speed over 3 years of follow‐up. This suggests that ICS may be a useful indicator of vascular brain damage leading to cognitive decline and may warrant consideration of antiatherosclerotic treatment in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited.Objective: This study investigated the role of SVD and NPS progressions on cognitive outcomes over 2 years in a dementia-free elderly cohort.Methods: 170 dementia-free elderly with baseline and 2-year neuropsychological assessments and MRI scans were included in this study. White matter hyperintensities (WMH), lacunes, and microbleeds (CMBs) were graded as markers of SVD. The Neuropsychiatric Inventory (NPI) was used to measure NPS. Generalized estimating equations modelling evaluated the relationship between NPI change and SVD progression. Logistic regression evaluated the risk of incident cognitive decline with both SVD and NPS. All models were adjusted for demographics, baseline cerebrovascular diease, and medial temporal lobe atrophy.Results: Higher NPI scores were associated with higher SVD burden at baseline. Subjects with WMH progression had greater increase in total NPI (β[SE] = 0.46[0.19], p = 0.016), driven by hyperactivity subsyndrome (β[SE] = 0.88[0.34], p = 0.007). Subjects with incident CMBs had greater increase in psychosis subsyndrome (β[SE] = 0.89[0.30], p < 0.001). Subjects with progressions in both SVD and NPS were more likely to develop cognitive decline over 2 years (OR[95% CI] = 4.17[1.06-16.40], p < 0.05).Conclusion: Our findings support worsening of NPS as a clinical indicator of SVD progression and are associated with cognitive decline over 2 years. Early detection of NPS and targeted interventions on SVD burden may improve NPS outcomes. [ABSTRACT FROM AUTHOR]

Background: Enlarged perivascular spaces (ePVS) are common finding on magnetic resonance imaging (MRI) in elderly. ePVS are thought to be associated with cerebral small vessel disease (SVD) such as white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs). However, the different location of SVD and its relationship to ePVS distribution requires further investigation. Objective: To study the association between location and severity of SVD with ePVS from memory clinic and population-based settings. Methods: This study includes patients from an ongoing memory clinic based case-control study and participants from the population-based: Epidemiology of Dementia in Singapore study (EDIS). All participants underwent a comprehensive standardized evaluation including physical, medical and neuropsychological assessment and a brain MRI. CMBs and lacune location were categorized into strictly lobar, strictly deep and mixed, and ePVS location into centrum semiovale and basal ganglia. WMH volume was automatically segmented and was classified into anterior and posterior distribution. Negative binomial regression models were constructed to analyse associations between SVD and ePVS and the rate ratios (RR) and 95% confidence intervals (CI) were reported. Results: Of 375 patients (median age = 73 years) from memory clinic and 583 participants (median age = 70 years) from EDIS, the median total ePVS count was 17.0 and 7.0, respectively. Increased severity of SVD was not associated with total ePVS counts in both memory clinic and EDIS study. Analysis with the location of SVD and ePVS also showed similar results. However, in EDIS study, presence of ≥2 lacunes [RR = 1.61, 95% CI = 1.3, 2.30, p = 0.009], presence of ≥2 CMBs [RR = 1.40, 95% CI = 1.08, 1.83, p = 0.012], and higher volume of WMH [RR = 1.41, 95% CI = 1.10, 1.81, p = 0.006] were associated with basal ganglia ePVS independent of age, gender and vascular risk factors. Conclusion: In this study, we found that the ePVS were not associated with the location and severity of SVD in the memory-clinic patients. However, only severity of SVD was associated with basal ganglia ePVS in the population-based setting. Our findings will need to be studied further in different cohorts so as to understand the mechanism underlying different SVD types in subclinical and clinical phases as well as for predicting cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (SVD) is one of the major contributors to cognitive impairment and dementia. However, data on the incidence and progression of SVD in an Asian population are lacking.Objective: The present study aims to investigate the incidence, progression, associated risk factors, and clinical relevance of SVD in a memory clinic setting.Methods: A prospective case-control study, where 346 patients underwent repeated brain MRI with a mean interval of 24.5 months, accessing white matter hyperintensities (WMH), lacunes and cerebral microbleeds (CMBs). Severity of cognitive impairment was assessed using Clinical Dementia Rating scale and change in clinical diagnosis. Data on demographics, vascular risk factors, and clinical history were collected at baseline.Results: The prevalence of significant WMH (Fazekas ≥2) was 56.6% at baseline which progressed to 59.0% at follow-up. Overall prevalence of CMBs increased from 42.2% to 47.4% (9% new cases) and lacunes increased from 31.8% to 33.2% (2.1% new cases). Hypertension was associated with WMH progression (OR: 1.78, 95% CI: 1.01, 2.99) and increasing age was associated with incident CMBs (OR: 1.04, 95% CI: 1.01, 1.08). Moreover, the use of lipid-lowering medications decreased the incidence of lacunes (OR: 0.15, 95% CI: 0.04, 0.61). The major risk factor for incident SVD was baseline SVD lesion load. WMH progression was associated with increased severity of cognitive impairment (OR: 1.95, 95% CI: 1.16, 3.23).Conclusion: Vascular risk factors and baseline severity of SVD lesion load were associated with progression of SVD. Furthermore, WMH progression was linked with increased severity of cognitive impairment. Future studies should be aimed to slow cognitive deterioration by preventing SVD related brain damage by targeting vascular risk factors. [ABSTRACT FROM AUTHOR]