Roberts, Rosebud O.

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

Hypertension is highly prevalent in the elderly population and microinfarcts are the most common vascular brain pathology identified in older adults at autopsy. We investigated the associations between systolic and diastolic blood pressures measured antemortem and the presence of microinfarcts at autopsy. Study subjects (n=302; age range=71-95) were participants in the population-based Mayo Clinic Study of Aging autopsy study, who had blood pressure measurements recorded during life. We investigated both cross-sectional systolic and diastolic blood pressure measurements at the baseline visit and the change in blood pressure (slope). Presence and location (subcortical or cortical) of chronic microinfarcts was abstracted from the autopsy reports. Of the 302 study subjects, 47 (16%) had cerebral microinfarcts, and, of those, 18 (38%) had subcortical microinfarcts and 29 (62%) had only cortical microinfarcts. The baseline blood pressures were not different between subjects with no microinfarcts, subcortical microinfarcts, and only cortical microinfarcts. In a logistic regression model including time between last blood pressure measurement and death, a greater decline in systolic [OR= 1.06 (1.01, 1.11); p=0.02]) and greater decline in diastolic [OR= 1.11 (1.02, 1.20); p=0.01] blood pressures were predictors of the presence of subcortical microinfarcts at autopsy. However, these variables were not associated with the presence of cortical microinfarcts. In conclusion, microinfarcts are common in the older adult population, and most of them are located in the cortex. A greater decline in both systolic and diastolic blood pressures and their association with subcortical microinfarcts, but not with cortical microinfarcts, may have implications for aggressive lowering of blood pressure in the elderly population.

AbstractObjectiveTo examine the association of baseline elevated brain amyloid and neurodegeneration with changes in activities of daily living in participants without dementia (ND; i.e., cognitively unimpaired and participants with mild cognitive impairment) at baseline in the population‐based Mayo Clinic Study of Aging.MethodsWe included 1747 ND participants with 11C‐PiB PET and MR imaging in the study, with data on activities of daily living (as assessed by the Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating scale Sum of Boxes for functional domains (CDR‐SOB (functional)), with a median (range) of 4.3 (0.0–12.7) years of follow‐up. Abnormal (elevated; A+) 11C‐PiB‐PET retention ratio was defined as standardized uptake value ratio ≥ 1.48, and abnormal (reduced) AD signature cortical thickness as ≤ 2.68 mm (neurodegeneration; N+). Associations were examined with mixed effects models, adjusting for age, sex, education, apolipoprotein E ε4 allele carrier status, and global cognitive z‐score.ResultsMean age (SD) was 71.4 years (10.1), 46.7% were females, 195 (11.2%) had A+N‐, 442 (25.3%) had A‐N+, and 339 (19.4%) had A+N+ biomarkers. The A+N+ group had the largest annualized change in the FAQ score from baseline (difference in annual change A+N+ vs. A‐N‐; ß (SE): 0.80 (0.07)); associations were substantially attenuated when a time‐varying global cognitive composite was included in the model (A+N+ vs. A‐N‐; ß (SE): 0.31 (0.05)). CDR‐SOB (functional) findings partly agreed with FAQ score findings.InterpretationThe longitudinal increase in functional limitations is greater for individuals with abnormal neuroimaging biomarkers, especially for those with both elevated brain amyloid and neurodegeneration.

OBJECTIVE To examine the association between being a medical doctor (MD) and the risk of incident dementia. DESIGN Cohort study. SETTING Olmsted County, Minnesota. PARTICIPANTS A total of 3460 participants (including 104 MDs), aged 70 years or older, of the population‐based Mayo Clinic Study of Aging. MEASUREMENTS Participants were randomly selected from the community and had comprehensive cognitive evaluations at baseline and approximately every 15 months to assess for diagnosis of dementia. For participants who withdrew from the follow‐up, dementia diagnosis was also assessed using information available in their medical record. The associations were examined using Cox proportional hazards models, adjusting for sex, education, and apolipoprotein E ε4, using age as the time scale. RESULTS MDs were older (vs “general population”), and most were males (93.3%). MDs without dementia at baseline did not have a significantly different risk for incident dementia (hazard ratio = 1.12; 95% confidence interval = 0.69‐1.82; P = .64) compared to the general population. CONCLUSIONS Although the study includes a small number of older, mainly male, MDs, it provides a preliminary insight on cognitive health later in life in MDs, while most previous studies examine the health of younger MDs. Larger longitudinal studies are needed to examine these associations and investigate if associations are modified by sex. J Am Geriatr Soc 68:1250–1255, 2020.