Citations

AbstractIntroductionEfforts to model the cost‐effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing‐home (NH) costs.MethodsA stratified‐random sample of Olmsted County, MN, residents ages 70–89 years (N = 3545), well‐characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider‐linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH‐use intensity (NH days/follow‐up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between‐category mean‐annual cost differences were adjusted for patient characteristics and follow‐up days.ResultsCosts/follow‐up day distributions differed significantly across cognitive categories. Mean costs/follow‐up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted‐between‐category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired.DiscussionCost‐effectiveness for managing/modifying both MCI and dementia should consider end‐of‐life costs and NH‐use intensity. Results can help inform cost‐effectiveness models, predict future‐care needs, and aid decision‐making by individuals/providers/payers/policymakers.

Abstract Normal brain aging is accompanied by patterns of functional and structural change. Alzheimer's disease (AD), a representative neurodegenerative disease, has been linked to accelerated brain aging at respective age ranges. Here, we developed a deep learning-based brain age prediction model using fluorodeoxyglucose (FDG) PET and structural MRI and tested how the brain age gap relates to degenerative cognitive syndromes including mild cognitive impairment, AD, frontotemporal dementia, and Lewy body dementia. Occlusion analysis, performed to facilitate interpretation of the model, revealed that the model learns an age- and modality-specific pattern of brain aging. The elevated brain age gap in dementia cohorts was highly correlated with the cognitive impairment and AD biomarker. However, regions generating brain age gaps were different for each diagnosis group of which the AD continuum showed similar patterns to normal aging in the CU.

Abstract Posterior cortical atrophy is a neurodegenerative syndrome with a heterogeneous clinical presentation due to variable involvement of the left, right, dorsal and ventral parts of the visual system, as well as inconsistent involvement of other cognitive domains and systems. 18F-fluorodeoxyglucose (FDG)-PET is a sensitive marker for regional brain damage or dysfunction, capable of capturing the pattern of neurodegeneration at the single-participant level. We aimed to leverage these inter-individual differences on FDG-PET imaging to better understand the associations of heterogeneity of posterior cortical atrophy. We identified 91 posterior cortical atrophy participants with FDG-PET data and abstracted demographic, neurologic, neuropsychological and Alzheimer’s disease biomarker data. The mean age at reported symptom onset was 59.3 (range: 45–72 years old), with an average disease duration of 4.2 years prior to FDG-PET scan, and a mean education of 15.0 years. Females were more common than males at 1.6:1. After standard preprocessing steps, the FDG-PET scans for the cohort were entered into an unsupervised machine learning algorithm which first creates a high-dimensional space of inter-individual covariance before performing an eigen-decomposition to arrive at a low-dimensional representation. Participant values (‘eigenbrains’ or latent vectors which represent principle axes of inter-individual variation) were then compared to the clinical and biomarker data. Eight eigenbrains explained over 50% of the inter-individual differences in FDG-PET uptake with left (eigenbrain 1) and right (eigenbrain 2) hemispheric lateralization representing 24% of the variance. Furthermore, eigenbrain-loads mapped onto clinical and neuropsychological data (i.e. aphasia, apraxia and global cognition were associated with the left hemispheric eigenbrain 1 and environmental agnosia and apperceptive prosopagnosia were associated with the right hemispheric eigenbrain 2), suggesting that they captured important axes of normal and abnormal brain function. We used NeuroSynth to characterize the eigenbrains through topic-based decoding, which supported the idea that the eigenbrains map onto a diverse set of cognitive functions. These eigenbrains captured important biological and pathophysiologic data (i.e. limbic predominant eigenbrain 4 patterns being associated with older age of onset compared to frontoparietal eigenbrain 7 patterns being associated with younger age of onset), suggesting that approaches that focus on inter-individual differences may be important to better understand the variability observed within a neurodegenerative syndrome like posterior cortical atrophy.

Background: The modifying effect of sex on the relation between marital status and dementia has yet to be determined. Objective: To examine if sex modifies the association between marital status and incident dementia. Methods: Population-based samples from the Mayo Clinic Study of Aging (MCSA, N = 3,471) and the Gothenburg H70 Birth Cohort Study (H70-study, N = 913) were used. A multiplicative interaction term was used to analyze the modifying effect of sex on the relation between marital status (married versus not married) and incident dementia using Cox regression models. Further, risk of dementia by marital status was also evaluated in models separated by sex. Results: In the MCSA, there was an interaction between marital status and sex in relation to dementia (p = 0.015). In contrast, in the H70-study, no significant interaction was observed (p = 0.28). Nevertheless, in both studies, not married men had increased risk of dementia compared to married men in models adjusted for age, education, and number of children (H70-study: 1.99; 1.06–3.76, MCSA: 1.43; 1.08–1.89). Associations remained similar after additional adjustment for depression, BMI, hypertension, dyslipidemia, and diabetes mellitus (H70-study: 2.00; 1.05–3.82, MCSA: 1.32; 0.99–1.76). Further, no significant association was observed between marital status and dementia in women (H70-study: 1.24; 0.82–1.89, MCSA: 0.82; 0.64–1.04). Conclusion: Sex had a modifying effect on the association between marital status and incident dementia. In analyses separated by sex, not married men had an increased risk of dementia compared to married men, while no significant association was observed between marital status and risk of dementia in women.

Background: Longitudinal, but not cross-sectional, cognitive testing is one option proposed to define transitional cognitive decline for individuals on the Alzheimer’s disease continuum. Objective: Compare diagnostic accuracy of cross-sectional subtle objective cognitive impairment (sOBJ) and longitudinal objective decline (ΔOBJ) over 30 months for identifying 1) cognitively unimpaired participants with preclinical Alzheimer’s disease defined by elevated brain amyloid and tau (A+T+) and 2) incident mild cognitive impairment (MCI) based on Cogstate One Card Learning (OCL) accuracy performance. Methods: Mayo Clinic Study of Aging cognitively unimpaired participants aged 50 + with amyloid and tau PET scans (n = 311) comprised the biomarker-defined sample. A case-control sample of participants aged 65 + remaining cognitively unimpaired for at least 30 months included 64 who subsequently developed MCI (incident MCI cases) and 184 controls, risk-set matched by age, sex, education, and visit number. sOBJ was assessed by OCL z-scores. ΔOBJ was assessed using within subjects’ standard deviation and annualized change from linear regression or linear mixed effects (LME) models. Concordance measures Area Under the ROC Curve (AUC) or C-statistic and odds ratios (OR) from conditional logistic regression models were derived. sOBJ and ΔOBJ were modeled jointly to compare methods. Results: sOBJ and ΔOBJ-LME methods differentiated A+T+ from A-T- (AUC = 0.64, 0.69) and controls from incident MCI (C-statistic = 0.59, 0.69) better than chance; other ΔOBJ methods did not. ΔOBJ-LME improved prediction of future MCI over baseline sOBJ (p = 0.003) but not over 30-month sOBJ (p = 0.09). Conclusion: Longitudinal decline did not offer substantial benefit over cross-sectional assessment in detecting preclinical Alzheimer’s disease or incident MCI.

Background: There is a need for feasible, scalable assessments to detect cognitive impairment and decline. The Cogstate Brief Battery (CBB) is validated for Alzheimer’s disease (AD) and in unsupervised and bring your own device contexts. The CBB has shown usability for self-completion in the home but has not been employed in this way in a multisite clinical trial in AD. Objective: The objective of the pilot was to evaluate feasibility of at-home, self-completion of the CBB in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) over 24 months. Methods: The CBB was included as a pilot for cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI-2, invited to take the assessment in-clinic, then at at-home over a period of 24 months follow-up. Data were analyzed to explore acceptability/usability, concordance of in-clinic and at-home assessment, and validity. Results: Data were collected for 104 participants (46 CN, 51 MCI, and 7 AD) who consented to provide CBB data. Subsequent analyses were performed for the CN and MCI groups only. Test completion rates were 100%for both the first in-clinic supervised and first at-home unsupervised assessments, with few repeat performances required. However, available follow-up data declined sharply over time. Good concordance was seen between in-clinic and at-home assessments, with non-significant and small effect size differences (Cohen’s d between -0.04 and 0.28) and generally moderate correlations (r = 0.42 to 0.73). Known groups validity was also supported (11/16 comparisons with Cohen’s d≥0.3). Conclusion: These data demonstrate the feasibility of use for the CBB for unsupervised at-home, testing, including MCI groups. Optimal approaches to the application of assessments to support compliance over time remain to be determined.