%0 Journal Article %J J Alzheimers Dis %D 2023 %T Alzheimer's Disease Pathology Outside of the Cerebrum Is Related to a Higher Odds of Dementia. %A Buchman, Aron S %A Leurgans, Sue E %A Kim, Namhee %A Agrawal, Sonal %A Oveisgharan, Shahram %A Zammit, Andrea R %A VanderHorst, Veronique %A Nag, Sukrit %A Bennett, David A %X

BACKGROUND: Assessments of Alzheimer's disease pathology do not routinely include lower brainstem, olfactory bulb, and spinal cord.

OBJECTIVE: Test if amyloid-β (Aβ) and paired helical filament (PHF) tau-tangles outside the cerebrum are associated with the odds of dementia.

METHODS: Autopsies were obtained in decedents with cognitive testing (n = 300). Aβ plaques and PHF tau-tangles were assessed in 24 sites: cerebrum (n = 14), brainstem (n = 5), olfactory bulb, and four spinal cord levels. Since spinal Aβ were absent in the first 165 cases, it was not assessed in the remaining cases.

RESULTS: Age at death was 91 years old. About 90% had Aβ in cerebrum and of these, half had Aβ in the brainstem. Of the latter, 85% showed Aβ in the olfactory bulb. All but one participant had tau-tangles in the cerebrum and 86% had brainstem tau-tangles. Of the latter, 80% had tau-tangles in olfactory bulb and 36% tau-tangles in one or more spinal cord levels. About 90% of adults with tau-tangles also had Aβ in one or more regions. In a logistic model controlling for demographics, Aβ and tau-tangles within the cerebrum, the presence of Aβ in olfactory bulb [OR, 1.74(1.00, 3.05)]; tau-tangles in brainstem [OR, 4.00(1.1.57,10.21)]; and spinal cord [OR, 1.87 (1.21,3.11)] were independently associated with higher odds of dementia.

CONCLUSION: Regional differences in Aβ and tau-tangle accumulation extend beyond cerebrum to spinal cord and their presence outside the cerebrum are associated with a higher odds of dementia. Further studies are needed to clarify the extent, burden, and consequences of AD pathology outside of cerebrum.

%B J Alzheimers Dis %V 96 %P 563-578 %8 2023 Nov 07 %G eng %N 2 %R 10.3233/JAD-230223 %0 Journal Article %J J Alzheimers Dis %D 2021 %T Latent Cognitive Class at Enrollment Predicts Future Cognitive Trajectories of Decline in a Community Sample of Older Adults. %A Zammit, Andrea R %A Yang, Jingyun %A Buchman, Aron S %A Leurgans, Sue E %A Muniz-Terrera, Graciela %A Lipton, Richard B %A Hall, Charles B %A Boyle, Patricia %A Bennett, David A %X

BACKGROUND: Methods that can identify subgroups with different trajectories of cognitive decline are crucial for isolating the biologic mechanisms which underlie these groupings.

OBJECTIVE: This study grouped older adults based on their baseline cognitive profiles using a latent variable approach and tested the hypothesis that these groups would differ in their subsequent trajectories of cognitive change.

METHODS: In this study we applied time-varying effects models (TVEMs) to examine the longitudinal trajectories of cognitive decline across different subgroups of older adults in the Rush Memory and Aging Project.

RESULTS: A total of 1,662 individuals (mean age = 79.6 years, SD = 7.4, 75.4%female) participated in the study; these were categorized into five previously identified classes of older adults differing in their baseline cognitive profiles: Superior Cognition (n = 328, 19.7%), Average Cognition (n = 767, 46.1%), Mixed-Domains Impairment (n = 71, 4.3%), Memory-Specific Impairment (n = 274, 16.5%), and Frontal Impairment (n = 222, 13.4%). Differences in the trajectories of cognition for these five classes persisted during 8 years of follow-up. Compared with the Average Cognition class, The Mixed-Domains and Memory-Specific Impairment classes showed steeper rates of decline, while other classes showed moderate declines.

CONCLUSION: Baseline cognitive classes of older adults derived through the use of latent variable methods were associated with distinct longitudinal trajectories of cognitive decline that did not converge during an average of 8 years of follow-up.

%B J Alzheimers Dis %V 83 %P 641-652 %8 2021 Sep 21 %G eng %N 2 %R 10.3233/JAD-210484 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Class-Specific Incidence of All-Cause Dementia and Alzheimer's Disease: A Latent Class Approach. %A Zammit, Andrea R %A Hall, Charles B %A Katz, Mindy J %A Muniz-Terrera, Graciela %A Ezzati, Ali %A Bennett, David A %A Lipton, Richard B %X

Identifying preclinical Alzheimer's disease (AD) is an important step toward developing approaches to early treatment and dementia prevention. We applied latent class analysis (LCA) to 10 baseline neuropsychological assessments for 1,345 participants from Einstein Aging Study. Time-to-event models for all-cause dementia and AD were run examining events in 4-year intervals. Five classes were identified: Mixed-Domain Impairment (n = 107), Memory-Specific Impairment (n = 457), Average (n = 539), Frontal Impairment (n = 118), and Superior Cognition (n = 124). Compared to the Average class, the Mixed-Domain Impairment and Memory-Specific Impairment classes were at higher risk of incident all-cause dementia and AD in the first 4 years from baseline, while the Frontal Impairment class was associated with higher risk between 4 and 8 years of follow-up. LCA identified classes which differ in cross-sectional cognitive patterns and in risk of dementia over specific follow-up intervals.

%B J Alzheimers Dis %V 66 %P 347-357 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/30282367?dopt=Abstract %R 10.3233/JAD-180604 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Subtypes Based on Neuropsychological Performance Predict Incident Dementia: Findings from the Rush Memory and Aging Project. %A Zammit, Andrea R %A Muniz-Terrera, Graciela %A Katz, Mindy J %A Hall, Charles B %A Ezzati, Ali %A Bennett, David A %A Lipton, Richard B %X

BACKGROUND: In a previous report, we used latent class analysis (LCA) to identify natural subgroups of older adults in the Einstein Aging Study (EAS) based on neuropsychological performance. These subgroups differed in demographics, genetic profile, and prognosis. Herein, we assess the generalizability of these findings to an independent sample, the Rush Memory and Aging Project (MAP), which used an overlapping, but distinct neuropsychological battery.

OBJECTIVE: Our aim was to identify the association of natural subgroups based on neuropsychological performance in the MAP cohort with incident dementia and compare them with the associations identified in the EAS.

METHODS: MAP is a community-dwelling cohort of older adults living in the northeastern Illinois, Chicago. Latent class models were applied to baseline scores of 10 neuropsychological measures across 1,662 dementia-free MAP participants. Results were compared to prior findings from the EAS.

RESULTS: LCA resulted in a 5-class model: Mixed-Domain Impairment (n = 71, 4.3%), Memory-specific-Impairment (n = 274, 16.5%), Average (n = 767, 46.1%), Frontal Impairment (n = 222, 13.4%), and a class of Superior Cognition (n = 328, 19.7%). Similar to the EAS, the Mixed-Domain Impairment, the Memory-Specific Impairment, and the Frontal Impairment classes had higher risk of incident Alzheimer's disease when compared to the Average class. By contrast, the Superior Cognition had a lower risk of Alzheimer's disease when compared to the Average class.

CONCLUSIONS: Natural cognitive subgroups in MAP are similar to those identified in EAS. These similarities, despite study differences in geography, sampling strategy, and cognitive tests, suggest that LCA is capable of identifying classes that are not limited to a single sample or a set of cognitive tests.

%B J Alzheimers Dis %8 2018 Nov 29 %G eng %R 10.3233/JAD-180737