Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old

Christian Lachner; Gregory S. Day; Gamze Balci Camsari; Naomi Kouri; Nilüfer Ertekin-Taner; Bradley F. Boeve; Sydney A. Labuzan; John A. Lucas; E. Aubrey Thompson; Habeeba Siddiqui; Julia E. Crook; Janisse N. Cabrera-Rodriguez; Keith A. Josephs; Ronald C. Petersen; Dennis W. Dickson; R. Ross Reichard; Michelle M. Mielke; David S. Knopman; Neill R. Graff-Radford; Melissa E. Murray

doi:10.3233/JAD-220440

Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old

Christian Lachner
, Gregory S. Day
, Gamze Balci Camsari
, Naomi Kouri
, Nilüfer Ertekin-Taner
, Bradley F. Boeve
, Sydney A. Labuzan
, John A. Lucas
, E. Aubrey Thompson
, Habeeba Siddiqui
, Julia E. Crook
, Janisse N. Cabrera-Rodriguez
, Keith A. Josephs
, Ronald C. Petersen
, Dennis W. Dickson
, R. Ross Reichard
, Michelle M. Mielke
, David S. Knopman
, Neill R. Graff-Radford
, Melissa E. Murray

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

BACKGROUND: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes.

OBJECTIVE: Investigate the contributions of vascular factors and cancer to dementia and neuropathology.

METHODS: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology.

RESULTS: Participants (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01).

CONCLUSION: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.

Original language	English (US)
Pages (from-to)	405-417
Number of pages	13
Journal	Journal of Alzheimer's Disease
Volume	90
Issue number	1
DOIs	https://doi.org/10.3233/JAD-220440
State	Published - Oct 25 2022

Bibliographical note

Publisher Copyright:
© 2022 – The authors. Published by IOS Press.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Aging
Alzheimer’s disease
cancer
dementia
neuropathology
vascular disease
Cerebrovascular Disorders/epidemiology
Diabetes Mellitus/epidemiology
Neuropathology
Comorbidity
Humans
Male
Coronary Artery Disease
Aged, 80 and over
Female
Apolipoproteins E
Alzheimer Disease/pathology
Plaque, Amyloid/pathology
Neoplasms/epidemiology
Nervous System Diseases

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

Publisher link

10.3233/JAD-220440

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Lachner, C., Day, G. S., Camsari, G. B., Kouri, N., Ertekin-Taner, N., Boeve, B. F., Labuzan, S. A., Lucas, J. A., Thompson, E. A., Siddiqui, H., Crook, J. E., Cabrera-Rodriguez, J. N., Josephs, K. A., Petersen, R. C., Dickson, D. W., Reichard, R. R., Mielke, M. M., Knopman, D. S., Graff-Radford, N. R., & Murray, M. E. (2022). Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old. Journal of Alzheimer's Disease, 90(1), 405-417. https://doi.org/10.3233/JAD-220440

Lachner, C, Day, GS, Camsari, GB, Kouri, N, Ertekin-Taner, N, Boeve, BF, Labuzan, SA, Lucas, JA, Thompson, EA, Siddiqui, H, Crook, JE, Cabrera-Rodriguez, JN, Josephs, KA, Petersen, RC, Dickson, DW, Reichard, RR, Mielke, MM, Knopman, DS, Graff-Radford, NR & Murray, ME 2022, 'Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old', Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 405-417. https://doi.org/10.3233/JAD-220440

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title = "Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old",

abstract = "BACKGROUND: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes.OBJECTIVE: Investigate the contributions of vascular factors and cancer to dementia and neuropathology.METHODS: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology.RESULTS: Participants (n = 161; 83\% female; 99\% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28\%]) versus dementia (11/88 [12\%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43\%]) versus dementia (23/89 [26\%]; p = 0.03) associated with 56\% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63\% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01).CONCLUSION: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.",

keywords = "Aging, Alzheimer{\textquoteright}s disease, cancer, dementia, neuropathology, vascular disease, Cerebrovascular Disorders/epidemiology, Diabetes Mellitus/epidemiology, Neuropathology, Comorbidity, Humans, Male, Coronary Artery Disease, Aged, 80 and over, Female, Apolipoproteins E, Alzheimer Disease/pathology, Plaque, Amyloid/pathology, Neoplasms/epidemiology, Nervous System Diseases",

author = "Christian Lachner and Day, \{Gregory S.\} and Camsari, \{Gamze Balci\} and Naomi Kouri and Nil{\"u}fer Ertekin-Taner and Boeve, \{Bradley F.\} and Labuzan, \{Sydney A.\} and Lucas, \{John A.\} and Thompson, \{E. Aubrey\} and Habeeba Siddiqui and Crook, \{Julia E.\} and Cabrera-Rodriguez, \{Janisse N.\} and Josephs, \{Keith A.\} and Petersen, \{Ronald C.\} and Dickson, \{Dennis W.\} and Reichard, \{R. Ross\} and Mielke, \{Michelle M.\} and Knopman, \{David S.\} and Graff-Radford, \{Neill R.\} and Murray, \{Melissa E.\}",

note = "Publisher Copyright: {\textcopyright} 2022 – The authors. Published by IOS Press.",

year = "2022",

month = oct,

day = "25",

doi = "10.3233/JAD-220440",

language = "English (US)",

volume = "90",

pages = "405--417",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

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TY - JOUR

T1 - Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old

AU - Lachner, Christian

AU - Day, Gregory S.

AU - Camsari, Gamze Balci

AU - Kouri, Naomi

AU - Ertekin-Taner, Nilüfer

AU - Boeve, Bradley F.

AU - Labuzan, Sydney A.

AU - Lucas, John A.

AU - Thompson, E. Aubrey

AU - Siddiqui, Habeeba

AU - Crook, Julia E.

AU - Cabrera-Rodriguez, Janisse N.

AU - Josephs, Keith A.

AU - Petersen, Ronald C.

AU - Dickson, Dennis W.

AU - Reichard, R. Ross

AU - Mielke, Michelle M.

AU - Knopman, David S.

AU - Graff-Radford, Neill R.

AU - Murray, Melissa E.

PY - 2022/10/25

Y1 - 2022/10/25

N2 - BACKGROUND: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes.OBJECTIVE: Investigate the contributions of vascular factors and cancer to dementia and neuropathology.METHODS: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology.RESULTS: Participants (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01).CONCLUSION: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.

AB - BACKGROUND: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes.OBJECTIVE: Investigate the contributions of vascular factors and cancer to dementia and neuropathology.METHODS: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology.RESULTS: Participants (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95-106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19-0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39-163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17-0.78]; p < 0.01) and lower Braak stage (p = 0.01).CONCLUSION: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.

KW - Aging

KW - Alzheimer’s disease

KW - cancer

KW - dementia

KW - neuropathology

KW - vascular disease

KW - Cerebrovascular Disorders/epidemiology

KW - Diabetes Mellitus/epidemiology

KW - Neuropathology

KW - Comorbidity

KW - Humans

KW - Male

KW - Coronary Artery Disease

KW - Aged, 80 and over

KW - Female

KW - Apolipoproteins E

KW - Alzheimer Disease/pathology

KW - Plaque, Amyloid/pathology

KW - Neoplasms/epidemiology

KW - Nervous System Diseases

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UR - https://www.scopus.com/pages/publications/85141003597#tab=citedBy

U2 - 10.3233/JAD-220440

DO - 10.3233/JAD-220440

M3 - Article

C2 - 36213996

AN - SCOPUS:85141003597

SN - 1387-2877

VL - 90

SP - 405

EP - 417

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 1

ER -

Cancer and Vascular Comorbidity Effects on Dementia Risk and Neuropathology in the Oldest-Old

Abstract

Bibliographical note

UN SDGs

Keywords

PubMed: MeSH publication types

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