Michelle R. Caunca

Cognitive correlates of white matter lesion load and brain atrophy: The Northern Manhattan Study

Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance.

Leisure-time physical activity associates with cognitive decline The Northern Manhattan Study

Objective: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. Methods: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). Results: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (β = −0.231 ± 0.112, p = 0.040) and episodic memory (β = −0.223 ± 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. Conclusions: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.

Cerebral Microbleeds, Vascular Risk Factors, and Magnetic Resonance Imaging Markers: The Northern Manhattan Study

Background Cerebral microbleeds (CMBs) represent intracerebral hemorrhages due to amyloid angiopathy or exposure to modifiable risk factors. Few community‐based stroke‐free studies including blacks and Hispanics have been done. Methods and Results The Northern Manhattan Study (NOMAS) is a stroke‐free, racially and ethnically diverse cohort study. Brain MRI was performed in 1290 participants, 925 of whom had available T2* gradient‐recall echo data. We used multivariable logistic regression to examine the association of sociodemographics, vascular risk factors, apolipoprotein E (APOE) genotype, and brain MRI markers with CMB presence and location. The prevalence of CMBs in our cohort was 5%. Of the 46 participants with CMBs, 37% had only deep CMBs, 48% had only lobar CMBs, and 15% had CMBs in both locations. The difference in CMB distribution was not statistically significant across race/ethnic group or APOE genotype. In multivariable analyses, age (OR [95% CI]: 1.09 [1.04, 1.15]) and SBIs (2.58 [1.01, 6.59]) were positively associated with CMB presence, and diabetes medication use was negatively associated (0.25 [0.07, 0.86]). Conclusions CMBs may represent the severity of vascular disease in this racially and ethnically diverse cohort. Larger studies are needed to elucidate the association between diabetes medication use and CMB presence.

Ultrasound Markers of Carotid Atherosclerosis and Cognition

Background and Purpose— Ultrasound markers of carotid atherosclerosis may be related to cognitive status. We hypothesized that individuals with greater carotid intima–media thickness (cIMT) and carotid plaque burden would exhibit worse cognition. Methods— One thousand one hundred sixty-six stroke-free participants from the NOMAS (Northern Manhattan Study) underwent carotid ultrasound and neuropsychological examination. Among them, 826 underwent a second neuropsychological examination an average of 5 years later. cIMT and plaque were assessed by a standardized B-mode ultrasound imaging and reading protocol. We used multivariable linear regression to examine cIMT, carotid plaque presence, and carotid plaque area as correlates of domain-specific neuropsychological Z scores cross-sectionally and over time. We also investigated possible effect modification by APOE &egr;4 allele, age, and race/ethnicity. Results— Participants had a mean (SD) age of 70 (9) years and were 60% women, 66% Hispanic, 15% white, and 18% black. Those with greater cIMT exhibited worse episodic memory after adjustment for demographics and vascular risk factors (&bgr;=−0.60; P=0.04). APOE &egr;4 carriers with greater cIMT exhibited worse episodic memory (&bgr;=−1.31; P=0.04), semantic memory (&bgr;=−1.45; P=0.01), and processing speed (&bgr;=−1.21; P=0.03). Participants with greater cIMT at baseline did not exhibit significantly greater cognitive decline after adjustment. APOE &egr;4noncarriers with greater cIMT exhibited greater declines in executive function (&bgr;=−0.98; P=0.06). Carotid plaque burden was not significantly associated with cognition at baseline or over time. Conclusions— Subclinical carotid atherosclerosis was associated with worse cognition among those at higher risk for Alzheimer disease. Interventions targeting early stages of atherosclerosis may modify cognitive aging.

Mediterranean Diet in Preventing Neurodegenerative Diseases

Purpose of ReviewWe reviewed the most recent literature examining the associations between the Mediterranean-style diet (MD), neurodegenerative diseases, and markers and mechanisms of neurodegeneration.Recent FindingsMost, but not all, epidemiologic studies report a protective association between MD adherence, cognitive impairment, and brain health. Data from clinical trials supporting these observational findings are also emerging. Limited evidence suggests that MD adherence may be protective for Parkinson’s disease risk. Mechanistically, plant polyphenols may activate similar molecular pathways as caloric restriction diets, which helps explain the neuroprotective properties of the MD.SummaryEvidence for cognitive disorders is abundant, but there is a dearth of literature for other neurodegenerative disorders and for markers of neurodegeneration. Further research is needed to elucidate the protective role of MD on neurodegeneration, the most salient components of the MD, and the most sensitive time periods over the lifecourse at which the MD may exert its effects.

MRI Markers Predict Cognitive Decline Assessed by Telephone Interview: The Northern Manhattan Study.

Background: Brain magnetic resonance imaging (MRI) allows researchers to observe structural pathology that may predict cognitive decline. Some populations are less accessible through traditional in-person visits, and may be under-represented in the literature. Methods: We examined white matter hyperintensity volume (WMHV) and cerebral parenchymal fraction (CPF) as predictors of cognitive decline measured by a modified Telephone Interview for Cognitive Status (TICS-m) in the Northern Manhattan Stroke Study, a racially and ethnically diverse cohort study. Participants were stroke-free, above 50 years old, and had no contraindications to MRI. A total of 1143 participants had MRI and TICS-m data available [mean age 70 (SD=9), 61% women, 66% Hispanic, 17% Black, 15% white]. Results: Those in the third and fourth quartiles of WMHV had significantly greater decline in TICS-m over time as compared with those in the first quartile (Q3: −0.17 points/year, Q4: −0.30 points/year). Those in the bottom 2 quartiles of CPF had significantly greater decline in TICS-m than those in the top quartile (Q1: −0.3 points/year, Q2: −0.2 points/year). Apolipoprotein E (APOE) e4 allele carriers had greater cognitive decline per unit of CPF. Those with greater CPF preserve TICS-m performance better despite greater WMHV. Conclusions: Telephone cognitive assessments can detect decline due to white matter lesions and smaller brain volumes.