Cognition and Amyloid-ß in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes.

Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. CONCLUSIONS: Psychiatric and health factors likely contributed to Group 2's low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans' co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.

Regional White Matter Hyperintensities Relate to Specific Cognitive Abilities in Older Adults Without Dementia.

INTRODUCTION: White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or total WMH; less is known about associations of regional WMHs and cognitive abilities among older adults without dementia. METHODS: A total of 610 older adults with normal cognition (n=302) or mild cognitive impairment (n=308) from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and magnetic resonance imaging. Linear regression models examined associations between regional WMH volumes and cognition, adjusting for age, sex, education, apolipoprotein E ε4 allele frequency, and pulse pressure. RESULTS: Among all participants, greater regional WMH volume in all lobes was associated with poorer performance on memory and speed/executive functioning. Among participants with normal cognition, greater temporal and occipital WMH volumes were associated with poorer memory, whereas no regional WMH volumes were associated with speed/executive function. DISCUSSION: Results show that greater regional WMH volume relates to poorer cognitive functioning-even among those with normal cognition. Together with results from previous studies, our findings raise the possibility that WMH may be a useful therapeutic target and/or important effect modifier in treatment or prevention dementia trials.

Associations Between Body Mass Index and Cognitive Change in the ACTIVE Study: Variations by Race and Social Determinants of Health.

Objectives: The current study examines relationships between Body Mass Index (BMI) and cognitive performance and change in processing speed, memory, and reasoning, while accounting for variations by race and the influence of social determinants of health. Methods: Secondary data analysis of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which included participants who self-identified as African American or Black (n = 728) and White (n = 2028). Latent growth curve modeling was used to assess study aims. Results: Increases in BMI were associated with less cognitive decline over 10 years across each cognition domain. Race moderation effects were noted for speed and memory. Relationships between BMI and cognitive trajectories were mediated by economic stability for speed and reasoning. Discussion: Overall, these findings are consistent with the "obesity paradox." Further research is needed to elucidate patterns of results by race.

Do Associations Between Vascular Risk and Mild Cognitive Impairment Vary by Race?

Objectives: Given prevalence differences of mild cognitive impairment (MCI) among Black and white older adults, this study aimed to examine whether overall vascular risk factor (VRF) burden and individual VRF associations with amnestic (aMCI) and nonamnestic (naMCI) MCI status varied by Black/white race. Methods: Participants included 2755 older adults without dementia from the ACTIVE study. Comprehensive neuropsychological criteria were used to classify cognitively normal, aMCI, and naMCI. VRFs were primarily defined using subjective report and medication data. Multinomial logistic regression was run predicting MCI subtype. Results: Greater overall VRF burden, high cholesterol, and obesity evinced greater odds of naMCI in Black participants than whites. Across participants, diabetes and hypertension were associated with increased odds of aMCI and naMCI, respectively. Discussion: Results may reflect known systemic inequities on dimensions of social determinants of health for Black older adults. Continued efforts toward examining underlying mechanisms contributing to these findings are critical.

HIV, Vascular Risk Factors, and Cognition in the Combination Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis.

OBJECTIVES: Mounting evidence indicates that vascular risk factors (VRFs) are elevated in HIV and play a significant role in the development and persistence of HIV-associated neurocognitive disorder. Given the increased longevity of people living with HIV (PLWH), there is a great need to better elucidate vascular contributions to neurocognitive impairment in HIV. This systematic review and meta-analysis examine relationships between traditional VRFs, cardiovascular disease (CVD), and cognition in PLWH in the combination antiretroviral therapy era. METHODS: For the systematic review, 44 studies met inclusion criteria and included data from 14,376 PLWH and 6,043 HIV-seronegative controls. To better quantify the contribution of VRFs to cognitive impairment in HIV, a robust variance estimation meta-analysis (N = 11 studies) was performed and included data from 2139 PLWH. RESULTS: In the systematic review, cross-sectional and longitudinal studies supported relationships between VRFs, cognitive dysfunction, and decline, particularly in the domains of attention/processing speed, executive functioning, and fine motor skills. The meta-analysis demonstrated VRFs were associated with increased odds of global neurocognitive impairment (odds ratio [OR ]= 2.059, p = .010), which remained significant after adjustment for clinical HIV variables (p = .017). Analyses of individual VRFs demonstrated type 2 diabetes (p = .004), hyperlipidemia (p = .043), current smoking (p = .037), and previous CVD (p = .0005) were significantly associated with global neurocognitive impairment. CONCLUSIONS: VRFs and CVD are associated with worse cognitive performance and decline, and neurocognitive impairment in PLWH. Future studies are needed to examine these relationships in older adults with HIV, and investigate how race/ethnicity, gender, medical comorbidities, and psychosocial factors contribute to VRF-associated cognitive dysfunction in HIV.

Differences in temporal order memory among young, middle-aged, and older adults may depend on the level of interference.

Age-related changes in temporal order memory have been well documented in older adults; however, little is known about this ability during middle age. We tested healthy young, middle-aged, and older adults on a previously published visuospatial temporal order memory test involving high and low interference conditions. When interference was low, young and middle-aged adults did not differ, but both groups significantly outperformed older adults. However, when interference was high, significant differences were found among all three age groups. The data provide evidence that temporal order memory may begin to decline in middle age, particularly when temporal interference is high.