Resting-state functional magnetic resonance imaging (rs-fMRI) allows estimation of individual-specific cortical parcellations. We have previously developed a multi-session hierarchical Bayesian model (MS-HBM) for estimating high-quality individual-specific network-level parcellations. Here, we extend the model to estimate individual-specific areal-level parcellations. While network-level parcellations comprise spatially distributed networks spanning the cortex, the consensus is that areal-level parcels should be spatially localized, that is, should not span multiple lobes. There is disagreement about whether areal-level parcels should be strictly contiguous or comprise multiple noncontiguous components; therefore, we considered three areal-level MS-HBM variants spanning these range of possibilities. Individual-specific MS-HBM parcellations estimated using 10 min of data generalized better than other approaches using 150 min of data to out-of-sample rs-fMRI and task-fMRI from the same individuals. Resting-state functional connectivity derived from MS-HBM parcellations also achieved the best behavioral prediction performance. Among the three MS-HBM variants, the strictly contiguous MS-HBM exhibited the best resting-state homogeneity and most uniform within-parcel task activation. In terms of behavioral prediction, the gradient-infused MS-HBM was numerically the best, but differences among MS-HBM variants were not statistically significant. Overall, these results suggest that areal-level MS-HBMs can capture behaviorally meaningful individual-specific parcellation features beyond group-level parcellations. Multi-resolution trained models and parcellations are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Kong2022_ArealMSHBM).
Elder mistreatment is recognized internationally as a prevalent and growing problem, meriting the attention of policymakers, practitioners, and the general public. Studies have demonstrated that elder mistreatment is sufficiently widespread to be a major public health concern and that it leads to a range of negative physical, psychological, and financial outcomes. This article provides an overview of key issues related to the prevention and treatment of elder mistreatment, focusing on initiatives that can be addressed by the White House Conference on Aging. We review research on the extent of mistreatment and its consequences. We then propose 3 challenges in preventing and treating elder mistreatment that relate to improving research knowledge, creating a comprehensive service system, and developing effective policy. Under each challenge, examples are provided of promising initiatives that can be taken to eliminate mistreatment. To inform the recommendations, we employed recent data from the Elder Justice Roadmap Project, in which 750 stakeholders in the field of elder mistreatment were surveyed regarding research and policy priorities.
ImportanceNational Institute on Aging–Alzheimer’s Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD).ObjectiveTo assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD.Design, Setting, and ParticipantsThis longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years.ExposuresBased on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T−, A−T+, A−T−). Presence (+) or absence (−) of neurodegeneration (N) was assessed using temporal cortical thickness.Main Outcomes and MeasuresEach cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups.ResultsAmong 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable.Conclusions and RelevanceThe clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.
Background: Major prevention trials for Alzheimer's disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In two cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-beta and tau deposits.Methods: Some 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD cohort) underwent amyloid and tau positron emission tomography (PET) and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the Dominantly Inherited AD (DIAN) cohort with amyloid PET and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results:In PREVENT-AD, lower neuroticism, neuropsychiatric burden and higher education were associated with less amyloid deposition (p=0.014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p=0.006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p=0.005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions:In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multi-domain interventions might help delay AD onset or progression.
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