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01-12-2019 | Autopsy | Original Communication

Cognitive function and neuropathological outcomes: a forward-looking approach

Authors: Elizabeth Munoz, Teresa Filshtein, Brianne M. Bettcher, Donald McLaren, Trey Hedden, Doug Tommet, Dan Mungas, Terry Therneau

Published in: Journal of Neurology | Issue 12/2019

Abstract

Objective

To evaluate the risk of Alzheimer’s disease-related neuropathology burden at autopsy given older adults’ current cognitive state.

Method

Participants included 1,303 individuals who enrolled in the Religious Orders Study (ROS) and 1,789 who enrolled in the Rush Memory and Aging Project (MAP). Cognitive status was evaluated via standardized assessments of global cognition and episodic memory. At the time of analyses, about 50% of participants were deceased with the remaining numbers right censored. Using multi-state Cox proportional hazard models, we compared the cognitive status of all subjects alive at a given age and estimated future risk of dying with different AD-related neuropathologies. Endpoints considered were Braak Stages (0–2, 3–4, 5–6), CERAD (0, 1, 2, 3), and TDP-43 (0, 1, 2, 3) level.

Results

For all three pathological groupings (Braak, CERAD, TDP-43), we found that a cognitive test score one standard deviation below average put individuals at up to three times the risk for being diagnosed with late stage AD at autopsy according to pathological designations. The effect remained significant after adjusting for sex, APOE-e4 status, smoking status, education level, and vascular health scores.

Conclusion

Applying multi-state modeling techniques, we were able to identify those at risk of exhibiting specific levels of neuropathology based on current cognitive test performance. This approach presents new and approachable possibilities in clinical settings for diagnosis and treatment development programs.

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Title: Cognitive function and neuropathological outcomes: a forward-looking approach
Authors: Elizabeth Munoz
Teresa Filshtein
Brianne M. Bettcher
Donald McLaren
Trey Hedden
Doug Tommet
Dan Mungas
Terry Therneau
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keywords: Autopsy
Alzheimer's Disease
Alzheimer's Disease
Pathology
Published in: Journal of Neurology / Issue 12/2019
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-019-09516-5

At a glance: The STEP trials

Springer Medicine

Cognitive function and neuropathological outcomes: a forward-looking approach

Abstract

Objective

Method

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Method

Results

Conclusion

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