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Background: The 2021 Alzheimer's Association International Conference press release forecasted global dementia cases to triple by 2050, due to the major contribution of increases in vascular risk factors. The Global Vascular Risk Score (GVRS) was developed to predict vascular events using a point‐based index for risk factor variables, though has demonstrated to be a significant predictor of global and domain‐specific cognitive performance in a multi‐ethnic cohort (Rundek, T. et al. Global Vascular Risk Score and CAIDE Dementia Risk Score Predict Cognitive Function in the Northern Manhattan Study. J Alzheimers Dis 73, 1221‐1231 (2020)). However, more than half of the variance in global and domain‐specific cognitive performance is still unexplained by GVRS variables. We sought to explain additional variance in cognitive performance by addition of MRI biomarkers of cerebral small vessel disease to the GVRS model. Method: We included 1290 subjects from the multiethnic Northern Manhattan Study population (age 64+/‐8 years, 40% women, 66% Hispanic, 17% non‐Hispanic Black, 15% non‐Hispanic White, education 10+/‐5 years). Multivariate linear regression models were employed to assess the added value of the cerebral small vessel disease MRI measures (white matter hyperintensity volume, silent brain infarcts, cerebral microbleeds, and perivascular spaces) beyond GVRS variables in explaining more variance in global and domain‐specific (episodic memory, executive function, semantic memory, and processing speed) cognitive performance. The explained variance (R2) of the GVRS model was compared to the proposed model with added imaging markers to determine their predictive performance. Statistical significance was determined using F‐statistic difference test between the models. Result: The explained variance (R2) and F‐statistic for models of global and domain‐specific cognition are in the table. Addition of MRI measures significantly improved the model for global cognition (F(4, 1108) = 2.68, p < 0.05) and domain‐specific cognitive performance models of episodic memory (F(4, 1096) = 3.34, p < 0.01) and processing speed (F(4, 1096) = 2.40, p < 0.05). Conclusion: MRI measures of cerebral small vessel disease explain more variance in global cognition, episodic memory, and processing speed than GVRS factors alone. However, most of the variance in cognitive performance remains unexplained. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's Disease (AD) is the most common cause of dementia, and the risk of developing AD increases with age. Age‐related cognitive decline (ARCD) refers to the cognitive changes that can occur in individuals because of aging. Research suggests that the underlying mechanism behind ARCD is a loss of synaptic plasticity and altered dendritic spine morphology. Similarly, the cognitive changes in AD are also thought to arise from impaired synaptic plasticity and dendritic spine loss. Souvenaid, contains a specific combination of precursors and cofactors for phospholipid biosynthesis, and has shown beneficial effects on memory, cognition, and brain atrophy in prodromal AD. In addition, data from this previous study imply a stronger effect would be expected in participants at earlier stages of prodromal AD. To test the effect of Souvenaid in ARCD, the REACTION (Reducing the Effects of Aging on Cognition with Therapeutic Intervention of an Oral multi‐Nutrient combination) pilot study was developed. Method: REACTION1 is a 6‐month single‐center randomized, double‐blind placebo‐controlled pilot clinical trial. The study factors in local COVID‐19 restrictions and is conducted fully virtually. Participants will be aged 55‐89 with ARCD, and screened and randomized to the oral multi‐nutrient combination (Souvenaid) or placebo on a 1:1 basis. The main outcome of this trial is feasibility (recruitment rate and time, adherence rate and retention rate). Other outcomes include memory (e.g. Ray Verbal Learning Task), cognition (e.g. Oral Trail Making Test), and quality of life (e.g. Amsterdam IADL Questionnaire) outcome measures. Result: Of 141 inquiries over 7 months, 60 eligible participants were recruited. 54 were successfully screened for randomization. As of 3 Feb 2022, 47 participants have been randomized to placebo or Souvenaid (6 are awaiting randomization, 1 withdrew prior to randomization.) Detailed baseline characteristics of the study population will be presented at the meeting, including descriptive statistics on demographics and the inclusion criteria such as the RBANS, MoCA and SCD 9‐item brief screening tool score. Conclusion: With the rapidly growing prevalence of ARCD and limited pharmacological curative treatment options currently available, nutritional interventions may potentially play an important role to prevent or delay the onset of ARCD. 1. Clinicaltrial.gov identifier: NCT04147624 [ABSTRACT FROM AUTHOR]

Background: PVS are fluid filled compartments surrounding small intracerebral vessels. They are conduits for fluid transport, exchange, and waste clearance. Their relationship to cardiovascular markers is unknown. We tested whether ePVS counts are affected by vascular risk factors and comorbidities. Method: We analyzed nondemented subjects’ brains from the FL‐VIP (comprised of 1Florida ADRC participants with available high quality 3T MRI). ePVS were defined as parenchymal hypo/hyperintensities of <3 mm seen on a single axial T1, T2 or FLAIR section through the basal ganglia (BG) and centrum semiovale (CSO). ePVS were defined as parenchymal hyperintensities <3 mm and graded as 0 (none), 1 (<10), 2 (11‐20), 3 (21‐40), and 4 (>40). The side with highest ePVS count was graded. BG and CSO scores were summed to yield a 0‐8 total. Generalized linear models were used to estimate ePVS score associations with demographics, vascular risk factors, and vascular comorbidities (VASCom score). Result: Of 228 non‐demented participants (mean age 72±8 years; 61% women, 60% Hispanic, mean education 15±4 years, 33% ApoE4 carriers), 59% were hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. ePVS scores ranged from 0‐7 (mean 2.5±1.4), 0‐4 for BG (mean 1.3±0.7) and CSO (mean 1.2 ±0.9). Majority of subjects (73%) had a total ePVS score greater than 1. In unadjusted analysis, BG ePVS were correlated with age (r=0.27, P<0.001), hypertension (r=0.19, p=0.008), MI/CHF/Angina (r=0.14, P=0.03), and coronary bypass (r=0.20, P=0.004). CSO ePVS were correlated with age (r=0.23, P=0.0005), obesity (r=‐0.15, p=0.03), and dyslipidemia (r=‐0.14, P=0.04). In multivariable stepwise regression analyses, BG ePVS were associated with age (β=0.024 per year, p=0.0001), being Hispanic (OR=0.21, P=0.035), coronary bypass (OR=0.70, p=0.025), and hypertension (OR =0.17, p=0.079). CSO PeVS were associated with age (β=0.028 per year, P<0.001) and dyslipidemia (OR=‐0.31, P=0.02). Conclusion: ePVS were more prevalent with aging, greater vascular risk burden, and Hispanic origin. Hypertension, cardiovascular disease and prior coronary bypass surgery were associated with ePVS in BG, but not in CSO. BG ePVS may be an important marker of small vessel disease linking vascular burden and cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: PVS are fluid filled compartments surrounding small intracerebral vessels. They are conduits for fluid transport, exchange, and waste clearance. ePVS are observed in AD, but their relation to SVD markers and neurodegeneration is unknown. We tested whether ePVS are correlated with markers of SVD but not cortical atrophy. Method: We analyzed subjects’ brains from the FL‐VIP (comprised of all 1Florida ADRC participants with high quality 3T MRI). ePVS were defined as parenchymal hypo/hyperintensities of <3 mm seen on a single axial T1,T2, or FLAIR section through the basal ganglia (BG) and centrum semiovale (CSO). ePVS were graded as 0 (none), 1 (<10), 2 (11‐20), 3 (21‐40), and 4 (>40). The side with highest ePVS count was graded. BGBG and CSO scores were summed to yield a 0‐8 ePVS total. Generalized linear models were used to estimate ePVS score associations with White‐Matter Hyperintensity Volume (WMHV), silent brain infarcts (SBIs), cerebral microbleeds (CMBs), and mean total cortical thickness. We adjusted for demographics, vascular risk factors and comorbidities, and ApoE4 status. Result: Of 228 non‐demented participants (mean age 72±8 years; 61% women, 60% Hispanic, mean education 15±4 years, 33% ApoE4 carriers), 59% were hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. 73% of subjects had a total ePVS score >1. Scores ranged from 0‐7 total (mean 2.5±1.4), 0‐4 for BG (mean 1.3±0.7) and CSO (1.2 ±0.9). In unadjusted analyses, total ePVS correlated with WMHV (r=0.46, p<0001), SBI (r=0.17, p=0.009), and CMB (r=0.16, p=0.016). BG ePVS correlated with WMHV, SBI and CMB. CSO ePVS correlated only with WMHV (r=0.32, p=0.002). In multivariable analyses, ePVS correlated with WMHV (β=4.97, p<0.001), SBI (OR=1.36, p=0.027), and CMB (OR=1.43, p=0.019). BG ePVS remained associated with WMHV, SBI and CMB; and CSO ePVS only with WMHV (β=4.70, p=0.039). Total, BG, and CSO ePVS were not associated with cortical thickness. Conclusion: BG ePVS are highly related to MRI markers of SVD, but not total cortical thickness, and therefore may be considered hallmark features of small vessel disease. CSO ePVS may not have as a prominent role in SVD. [ABSTRACT FROM AUTHOR]