Petersen, Ronald C.

ObjectiveTo investigate the multifactorial processes underlying cognitive aging based on the hypothesis that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual through worsening brain health.MethodsWe identified 1,230 elderly subjects (aged ≥50 years) with an average of 4.9 years of clinical follow‐up and with amyloid positron emission tomography, diffusion tensor imaging, and structural magnetic resonance imaging scans from the population‐based Mayo Clinic Study of Aging. We examined imaging markers of amyloid and brain health (white matter microstructural integrity and cortical thinning), systemic vascular health preceding the imaging markers, and early to midlife intellectual enrichment to predict longitudinal cognitive trajectories. We used latent growth curve models for modeling longitudinal cognitive decline.ResultsAll the pathways (amyloid, vascular, resilience) converged through their effects on cortical thinning and worsening cognition and together explained patterns in cognitive decline. Resilience and vascular pathways (aging process, sex differences, education/occupation, and systemic vascular health) had significant impact on white matter microstructural integrity. Education/occupation levels contributed to white matter integrity through systemic vascular health. Worsening white matter integrity contributed to significant cortical thinning and subsequently longitudinal cognitive decline. Baseline amyloidosis contributed to a significant proportion of cognitive decline that accelerated with longer follow‐up times, and its primary impact was through cortical thinning.InterpretationWe developed an integrated framework to help explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important for both better comprehension of cognitive aging processes and will aid in the development of successful intervention strategies. ANN NEUROL 2019;86:866–877

AbstractIntroductionOur aim was to examine whether surgery with regional anesthesia (RA) is associated with accelerated long‐term cognitive decline comparable with that previously reported after general anesthesia (GA).MethodsLongitudinal cognitive function was analyzed in a cohort of 1819 older adults. Models assessed the rate of change in global and domain‐specific cognition over time in participants exposed to RA or GA.ResultsWhen compared with those unexposed to anesthesia, the postoperative rate of change of the cognitive global z‐score was greater in those exposed to both RA (difference in annual decline of −0.041, P = .011) and GA (−0.061, P < .001); these rates did not differ. In analysis of the domain‐specific scores, an accelerated decline in memory was observed after GA (−0.065, P < .001) but not RA (−0.011, P = .565).ConclusionsOlder adults undergoing surgery with RA experience decline of global cognition similar to those receiving GA; however, memory was not affected.

See Gordon and Tijms (doi:10.1093/brain/awz278) for a scientific commentary on this article. Jack et al. examine relationships between the bivariate distribution of β-amyloid and tau on PET and established neurocognitive clinical syndromes. Amyloidosis appears to be required for high levels of 3R/4R tau deposition. Whereas abnormal amyloid PET is compatible with normal cognition, highly abnormal tau PET is not.

AbstractBackground: hearing loss has been associated with mild cognitive impairment (MCI) and dementia. Studies have not assessed whether hearing difficulties (HD) that interfere with daily activities as reported by partners can be a marker for increased risk for cognitive decline and impairment.Objective: to assess the cross-sectional and longitudinal associations between informant-based HD, which interfere with daily activities and the risk for MCI and dementia.Methods: the study included 4812 participants without dementia, enrolled in the Mayo Clinic Study of Aging (mean age (SD) 73.7 (9.6) years) with cognitive evaluation and informant-based report on participant’s HD that interfere significantly with daily activities at baseline and for every 15 months. Cox proportional hazards models (utilising time-dependent HD status and age as the time scale) were used to examine HD and the risk for MCI or dementia, and mixed-effects models (allowing for random subject-specific intercepts and slopes) were used to examine the relationship between HD and cognitive decline.Results: about, 981 participants had HD and 612 (12.7%) had prevalent MCI at baseline; 759 participants developed incident MCI and 273 developed incident dementia. In cognitively unimpaired participants at baseline, those with HD had higher risk for MCI (hazard ratio [HR] = 1.29, 95% confidence interval [CI] (1.10, 1.51), P = 0.002; adjusting for sex, years of education). In participants without dementia, those with HD had higher risk for dementia (HR: 1.39, 95% CI, (1.08–1.79), P = 0.011; adjusting sex and education). In individuals with MCI, HD was associated with modestly greater cognitive decline.Conclusions: informant-based HD was associated with increased risk for MCI and dementia.

Abstract Introduction Neuroimaging biomarkers are important for early diagnosis of Alzheimer's disease, and comparing multimodality neuroimaging to autopsy data is essential. Methods We compared the pathologic findings from a prospective autopsy cohort (n = 100) to Pittsburgh compound B PET (PiB‐PET), 18 F‐fluorodeoxyglucose PET (FDG‐PET), and MRI. Correlations between neuroimaging biomarkers and neuropathologic schemes were assessed. Results PiB‐PET showed strong correlations with Thal amyloid phase and Consortium to Establish a Registry for Alzheimer's Disease score and categorized 44% of Thal phase 1 participants as positive. FDG‐PET and MRI correlated modestly with Braak tangle stage in Alzheimer's type pathology. A subset of participants with “none” or “sparse” neuritic plaque scores had elevated PiB‐PET signal due to diffuse amyloid plaque. Participants with findings characterized as “suspected non‐Alzheimer's pathophysiology” represented 15% of the group. Discussion PiB‐PET is associated with Alzheimer's disease, neuritic plaques, and diffuse plaques. FDG‐PET and MRI have modest correlation with neuropathologic schemes. Participants with findings characterized as suspected non‐Alzheimer's pathophysiology most commonly had primary age‐related tauopathy.