Petersen, Ronald C.

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.

ObjectiveTo investigate β‐amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients.MethodsPatients with MS (n = 16) and controls (n = 80) matched for age, sex, andAPOEε4 status from the population‐based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age.ResultsAD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98],p= 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99],p= 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90],p= 0.040) were lower in MS than controls. Although AD‐signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35],p= 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006],p= 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005],p= 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls.InterpretationAlthough both β‐amyloid and tau are biomarkers of cognitive aging and AD, cortical β‐amyloid deposition was lower in MS than age‐matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β‐amyloid but not the accumulation of tau.ANN NEUROL 2020;87:556–567

Background: Transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with hippocampal atrophy in Alzheimer’s disease (AD), but whether the association is modified by other factors is unknown. Objective: To evaluate whether the associations between TDP-43 and hippocampal volume and atrophy rate are affected by age, gender, apolipoprotein E ( APOE) ɛ4, Lewy bodies (LBs), amyloid-β (Aβ), or Braak neurofibrillary tangle (NFT) stage. Methods: In this longitudinal neuroimaging-clinicopathological study of 468 cases with AD neuropathological changes (Aβ-positive) that had completed antemortem head MRI, we investigated how age, gender, APOE ɛ4, presence of LBs, Aβ, TDP-43, and Braak NFT stages are associated with hippocampal volumes and rates of atrophy over time. We included field strength in the models since our cohort included 1.5T and 3T scans. We then determined whether the associations between hippocampal atrophy and TDP-43 are modified by these factors using mixed effects models. Results: Older age, female gender, APOE ɛ4, higher field strength, higher TDP-43, and Braak NFT stages were associated with smaller hippocampi. Rate of atrophy was greater with higher TDP-43 and Braak NFT stage, but lower in older patients. The association of TDP-43 with greater rate of atrophy was enhanced in APOE ɛ4 carriers ( p = 0.04). Conclusion: Neurodegenerative effects of TDP-43 seem to be independent of most factors except perhaps APOE in cases with AD neuropathological changes. TDP-43 and tau appear to behave independently of one another.