Mielke, Michelle M.

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

Introduction: The association of prostate cancer and androgen deprivation therapy (ADT) use with the odds of developing mild cognitive impairment (MCI) was determined in men from the population-based Mayo Clinic Study of Aging (MCSA). Methods: The study included 2513 men (mean age of 73.1 y) enrolled in the MCSA. A history of prostate cancer, ADT use, and length of ADT exposure before their first MCSA visit was abstracted using the Rochester Epidemiology Project medical records-linkage system. MCI was diagnosed at the baseline visit. Logistic regression was used to determine whether prostate cancer and ADT use was associated with odds of MCI. Results: Of the 2513 participants, 349 (13.9%) had a history of prostate cancer; among whom 99 (28.3%) were treated with ADT before MCSA enrollment. There were 382 (15.2%) with a diagnosis of MCI. In the univariate logistic regression models, prostate cancer (odds ratio, 1.50; 95% confidence interval, 1.12-2.00), and ADT exposure (odds ratio, 1.57; 95% confidence interval, 0.96-2.58) were associated with higher odds of MCI. These associations were greatly attenuated and not significant in multivariable models. Conclusions: Neither a diagnosis of prostate cancer nor ADT use was associated with odds of MCI in this cross-sectional population-based study.

Abstract Background The development of cerebrospinal fluid and blood-based biomarkers for Alzheimer disease (AD) and related disorders is rapidly progressing. Such biomarkers may be used clinically to screen the population, to enhance diagnosis, or to help determine prognosis. Although the use of precision medicine methods has contributed to enhanced understanding of the AD pathophysiological changes and development of assays, one aspect not commonly considered is sex differences. Content There are several ways in which sex can affect the concentration or interpretation of biofluid biomarkers. For some markers, concentrations will vary by sex. For others, the concentrations might not vary by sex, but the impact or interpretation may vary by sex depending on the context of use (e.g., diagnostic vs prognostic). Finally, for others, there will be no sex differences in concentrations or their interpretation. This review will first provide a basis for sex differences, including differences in brain structure and function, and the means by which these differences could contribute to sex differences in biomarker concentrations. Next, the current state of sex differences in AD-related biofluid markers (i.e., amyloid-β, phosphorylated τ, total τ, neurofilament light chain, and neurogranin) will be reviewed. Lastly, factors that can lead to the misinterpretation of observed sex differences in biomarkers (either providing evidence for or against) will be considered. Summary This review is intended to provide an impetus to consider sex differences in the measurement and interpretation of AD-related biofluid-based biomarkers.

AbstractIntroductionFrontotemporal dementia disorders (FTDs) are heterogeneous phenotypical behavioral and language disorders usually associated with frontal and/or temporal lobe degeneration. We investigated their incidence in a population‐based cohort.MethodsUsing a records‐linkage system, we identified all patients with a diagnostic code for dementia in Olmsted County, MN, 1995–2010, and confirmed the diagnosis of FTD. A behavioral neurologist verified the clinical diagnosis and determined phenotypes.ResultsWe identified 35 FTDs cases. Overall, the incidence of FTDs was 4.3/100,000/year (95% CI: 2.9, 5.7). Incidence was higher in men (6.3/100,000, 95% CI 3.6, 9.0) than women (2.9/100,000; 95% CI: 1.3, 4.5); we observed an increased trend over time (B = 0.83, 95% CI: 0.54, 1.11, P < .001). At autopsy, clinical diagnosis was confirmed in eight (72.7%) cases.DiscussionWe observed an increased incidence and trends of FTDs over time. This may reflect a better recognition by clinicians and improvement of clinical criteria and diagnostic tools.

Abstract Recent study has shown that incident dementia risk is higher among older persons who decline in both cognition and gait. This study assesses whether this relationship exists in multiple other aging populations. Data are from the Baltimore Longitudinal Study of Aging (n=662, 51%women,22%blacks), Health, Aging and Body Composition Study (n=746, 51%women,44%blacks), and Mayo Clinic Study of Aging (n=2771, 48%women,0.3%blacks). Participants were at least 60, initially free of cognitive impairment, dementia, and dismobility (gait speed≤0.6m/s), with repeated measures of verbal memory and gait speed before dementia diagnosis (average follow-up 5.8-12.1 years). Within each cohort, participants were divided into four groups: memory decliners alone, gait decliners alone, dual decliners, or neither (healthy agers). Gait speed decline was defined as a loss of ≥0.05m/sec/year; memory decline was defined as cohort specific bottom slope tertile. Incident dementia risk was examined by Cox regression with healthy agers as reference, adjusted for sex, race, baseline age, gait speed and memory. Across studies, incident dementia ranged from 3% to 17%. Compared to healthy agers, memory decliners alone had 3.4 to 4.3 times higher risk for developing dementia (p&lt;0.01). Gait decliners alone had 2.1-5.6 times higher risk for dementia (p&lt;0.05). Dual decliners had 7.6-10.8 times the risk (p&lt;0.001). Dual decline signifies a more rapid progression to dementia. These consistent findings suggest that dual decliners might be a potentially valuable target group for both preventive interventions and mechanistic studies. Whether dual decline identifies a particular subtype or multiple subtypes of dementia remains to be investigated.