Ecology of the aging human brain

Joshua A. Sonnen, Karen Santa Cruz, Laura S. Hemmy, Randall (Randy) Woltjer, James B. Leverenz, Kathleen S. Montine, Clifford R. Jack, Jeffrey Kaye, Kelvin Lim, Eric B. Larson, Lon White, Thomas J. Montine

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Background: Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. Objective: To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Design: Autopsy study. Setting: Community- and population based. Participants: A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Main Outcome Measures: Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Results: Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these,6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. Conclusions: These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.

Original languageEnglish (US)
Pages (from-to)1049-1056
Number of pages8
JournalArchives of Neurology
Volume68
Issue number8
DOIs
StatePublished - Aug 2011

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Lewy Body Disease
Ecology
Neurofibrillary Tangles
Amyloid Plaques
Cerebrovascular Trauma
Autopsy
Brain
Population
Brain Diseases
Substantia Nigra
Neuroimaging
Dementia
Comorbidity
Alzheimer Disease
Biomarkers
Outcome Assessment (Health Care)
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sonnen, J. A., Santa Cruz, K., Hemmy, L. S., Woltjer, R. R., Leverenz, J. B., Montine, K. S., ... Montine, T. J. (2011). Ecology of the aging human brain. Archives of Neurology, 68(8), 1049-1056. https://doi.org/10.1001/archneurol.2011.157

Ecology of the aging human brain. / Sonnen, Joshua A.; Santa Cruz, Karen; Hemmy, Laura S.; Woltjer, Randall (Randy); Leverenz, James B.; Montine, Kathleen S.; Jack, Clifford R.; Kaye, Jeffrey; Lim, Kelvin; Larson, Eric B.; White, Lon; Montine, Thomas J.

In: Archives of Neurology, Vol. 68, No. 8, 08.2011, p. 1049-1056.

Research output: Contribution to journalArticle

Sonnen, JA, Santa Cruz, K, Hemmy, LS, Woltjer, RR, Leverenz, JB, Montine, KS, Jack, CR, Kaye, J, Lim, K, Larson, EB, White, L & Montine, TJ 2011, 'Ecology of the aging human brain', Archives of Neurology, vol. 68, no. 8, pp. 1049-1056. https://doi.org/10.1001/archneurol.2011.157
Sonnen JA, Santa Cruz K, Hemmy LS, Woltjer RR, Leverenz JB, Montine KS et al. Ecology of the aging human brain. Archives of Neurology. 2011 Aug;68(8):1049-1056. https://doi.org/10.1001/archneurol.2011.157
Sonnen, Joshua A. ; Santa Cruz, Karen ; Hemmy, Laura S. ; Woltjer, Randall (Randy) ; Leverenz, James B. ; Montine, Kathleen S. ; Jack, Clifford R. ; Kaye, Jeffrey ; Lim, Kelvin ; Larson, Eric B. ; White, Lon ; Montine, Thomas J. / Ecology of the aging human brain. In: Archives of Neurology. 2011 ; Vol. 68, No. 8. pp. 1049-1056.
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abstract = "Background: Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. Objective: To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Design: Autopsy study. Setting: Community- and population based. Participants: A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Main Outcome Measures: Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Results: Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these,6{\%} also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8{\%} also had nigral and 4{\%} isocortical LBD. The presence of any cerebral microinfarcts was identified in 33{\%} and of high-level cerebral microinfarcts in 10{\%} of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. Conclusions: These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.",
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AU - Woltjer, Randall (Randy)

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AU - Montine, Kathleen S.

AU - Jack, Clifford R.

AU - Kaye, Jeffrey

AU - Lim, Kelvin

AU - Larson, Eric B.

AU - White, Lon

AU - Montine, Thomas J.

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N2 - Background: Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. Objective: To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Design: Autopsy study. Setting: Community- and population based. Participants: A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Main Outcome Measures: Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Results: Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these,6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. Conclusions: These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.

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