TY - JOUR
T1 - Cognitive function and neuropathological outcomes
T2 - a forward-looking approach
AU - Munoz, Elizabeth
AU - Filshtein, Teresa
AU - Bettcher, Brianne M.
AU - McLaren, Donald
AU - Hedden, Trey
AU - Tommet, Doug
AU - Mungas, Dan
AU - Therneau, Terry
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Cognition
KW - Multi-state model
KW - Neuropathology
UR - http://www.scopus.com/inward/record.url?scp=85071272050&partnerID=8YFLogxK
U2 - 10.1007/s00415-019-09516-5
DO - 10.1007/s00415-019-09516-5
M3 - Article
C2 - 31435771
AN - SCOPUS:85071272050
SN - 0340-5354
VL - 266
SP - 2920
EP - 2928
JO - Journal of Neurology
JF - Journal of Neurology
IS - 12
ER -