Cognitive function and neuropathological outcomes: a forward-looking approach

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of Neurology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Cognition
Autopsy
Episodic Memory
Proportional Hazards Models
Health Status
Blood Vessels
Alzheimer Disease
Smoking
Education
Neuropathology

Keywords

  • Alzheimer’s disease
  • Cognition
  • Multi-state model
  • Neuropathology

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Munoz, E., Filshtein, T., Bettcher, B. M., McLaren, D., Hedden, T., Tommet, D., ... Therneau, T. (Accepted/In press). Cognitive function and neuropathological outcomes: a forward-looking approach. Journal of Neurology. https://doi.org/10.1007/s00415-019-09516-5

Cognitive function and neuropathological outcomes : a forward-looking approach. / Munoz, Elizabeth; Filshtein, Teresa; Bettcher, Brianne M.; McLaren, Donald; Hedden, Trey; Tommet, Doug; Mungas, Dan M; Therneau, Terry.

In: Journal of Neurology, 01.01.2019.

Research output: Contribution to journalArticle

Munoz, Elizabeth ; Filshtein, Teresa ; Bettcher, Brianne M. ; McLaren, Donald ; Hedden, Trey ; Tommet, Doug ; Mungas, Dan M ; Therneau, Terry. / Cognitive function and neuropathological outcomes : a forward-looking approach. In: Journal of Neurology. 2019.
@article{b29f42cb524a4ceea07bf7abfaca18e8,
title = "Cognitive function and neuropathological outcomes: a forward-looking approach",
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.",
keywords = "Alzheimer’s disease, Cognition, Multi-state model, Neuropathology",
author = "Elizabeth Munoz and Teresa Filshtein and Bettcher, {Brianne M.} and Donald McLaren and Trey Hedden and Doug Tommet and Mungas, {Dan M} and Terry Therneau",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00415-019-09516-5",
language = "English (US)",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "D. Steinkopff-Verlag",

}

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 M

AU - Therneau, Terry

PY - 2019/1/1

Y1 - 2019/1/1

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

UR - http://www.scopus.com/inward/citedby.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

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

ER -