2 results
13 Regional White Matter Hyperintensities are Associated with Cognition in Prospective Alzheimer’s Clinical Trial Participants
- Clarissa D. Morales, Dejania Cotton-Samuel, Kay C. Igwe, Patrick J. Lao, Julia F. Chang, Amirreza Sedaghat, Mohamad J. Alshikho, Rafael Lippert, Kelsang C. Bista, Kacie Deters, Molly E. Zimmerman, Adam M. Brickman
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 224-225
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Previous research established that white matter hyperintensities (WMH), a biomarker of small vessel cerebrovascular disease, are strong predictors of cognitive function in older adults and associated with clinical presentation of Alzheimer’s disease (AD), particularly when distributed in posterior brain regions. Secondary prevention clinical trials, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, target amyloid accumulation in asymptomatic amyloid positive individuals, but it is unclear the extent to which small vessel cerebrovascular disease accounts for performance on the primary cognitive outcomes in these trials. The purpose of this study was to examine the relationship between regional WMH volume and performance on the Preclinical Alzheimer Cognitive Composite (PACC) among participants screened for participation in the A4 trial. We also determined whether the association between WMH and cognition is moderated by amyloid positivity status.
Participants and Methods:We assessed demographic, amyloid PET status, cognitive screening, and raw MRI data for participants in the A4 trial and quantitated regional (by cerebral lobe) WMH volumes from T2-weighted FLAIR in amyloid positive and amyloid negative participants at screening. Cognition was assessed using PACC scores, a z-score sum of four cognitive tests: The Mini-Mental State Examination (MMSE), the Free and Cued Selective Reminding Test, Logical Memory Test, and Digit Symbol Substitution Test. We included 1329 amyloid positive and 329 amyloid negative individuals (981 women; mean age=71.79 years; mean education=16.58 years) at the time of the analysis. The sample included Latinx (n=50; 3%), non-Latinx (n=1590; 95.9%), or unspecified ethnicity (n=18; 1.1%) individuals who identified as American Indian/Alaskan Native (n=7; 0.4%), Asian (n=38; 2.3%), Black/African American (n=41; 2.5%), White (n=1551 ; 93.5%), or unspecified (n=21; 1.3%) race. We first examined the associations of total and regional WMH volume and amyloid positivity on PACC scores (the primary cognitive outcome measure for A4) using separate general linear models and then determined whether amyloid positivity status and regional WMH statistically interacted for those WMH regions that showed significant main effects.
Results:Both increased WMH, in the frontal and parietal lobes particularly, and amyloid positivity were independently associated with poorer performance on the PACC, with similar magnitude. In subsequent models, WMH volume did not interact with amyloid positivity status on PACC scores.
Conclusions:Regionally distributed WMH are independently associated with cognitive functioning in typical participants enrolled in a secondary prevention clinical trial for AD. These effects are of similar magnitude to the effects of amyloid positivity on cognition, highlighting the extent to which small vessel cerebrovascular disease potentially drives AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered explicitly when evaluating outcomes in trials, both as potential effect modifiers and as possible targets for intervention or prevention. The findings from this study cannot be generalized widely, as the participants are not representative of the overall population.
6 Racial Discrimination and White Matter Integrity Among Black Older Adults
- Jordan D Palms, Mohamad J. Alshikho, Patrick J. Lao, Clarissa D. Morales, Jennifer J. Manly, Nicole Schupf, Adam M. Brickman, Laura B. Zahodne
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 788-789
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Non-Hispanic Black older adults experience a disproportionate burden of Alzheimer’s Disease and related dementias (ADRD) risk compared to non-Hispanic White older adults. It is necessary to identify mechanisms that may be contributing to inequities in cognitive aging. Psychosocial stressors that disproportionately affect Black adults (e.g., discrimination) have the potential to impact brain health through stress pathways. The brain’s white matter, which appears to be particularly important for ADRD risk among Black older adults, may be uniquely vulnerable to stress-related physiological dysfunction. To further understand whether and how discrimination can affect ADRD risk, this study aimed to examine associations between multiple forms of racial discrimination and white matter integrity, operationalized through diffusion tensor imaging.
Participants and Methods:Cross-sectional data were obtained from 190 non-Hispanic Black residents aged 65+ without dementia in northern Manhattan. Racial discrimination was self-reported using the Everyday Discrimination and Major Experiences of Lifetime Discrimination scales. Example items from the Everyday Discrimination Scale include: “You are treated with less respect than other people”; “You are called names or insulted.” Example items from the Major Experiences of Lifetime Discrimination Scale include: “At any time in your life, have you ever been unfairly fired from a job?”; “Have you ever been unfairly denied a bank loan?” Racial discrimination was operationalized as experiences attributed to “race” or “skin color.” White matter integrity was assessed using fractional anisotropy (FA) via diffusion tensor imaging. Multivariable regression models evaluated the unique effects of everyday and major experiences of lifetime racial discrimination on mean FA in the whole brain and specific regions. Initial models controlled for age, sex/gender, intracranial volume, and white matter hyperintensities. Subsequent models additionally controlled for socioeconomic and health factors to consider potential confounders or mediators of the relationship between discrimination and white matter integrity.
Results:Major experiences of lifetime discrimination were negatively associated with mean FA within the left cingulum cingulate gyrus and the right inferior fronto-occipital fasciculus. These associations persisted when controlling for additional covariates (i.e., education, depression, and cardiovascular diseases). In contrast, major experiences of lifetime discrimination were positively associated with mean FA within the right superior longitudinal fasciculus (temporal part). This association was attenuated when controlling for additional covariates. Everyday racial discrimination was not associated with mean FA in any regions.
Conclusions:These results extend prior work linking racial discrimination to brain health and provide evidence for both risk and resilience among Black older adults. Major experiences of lifetime racial discrimination, a proxy for institutional racism, may have a stronger effect on white matter integrity than everyday racial discrimination, a proxy for interpersonal racism. Educational opportunities and cardiovascular risk factors may represent mediators between racial discrimination and white matter integrity. White matter integrity within specific brain regions may be a mechanism through which racially patterned social stressors contribute to racial disparities in ADRD. Future research should characterize within-group heterogeneity in order to identify factors that promote resilience among Black older adults.