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NEUROLOGY 2009;72:354-360
© 2009 American Academy of Neurology

Factors associated with resistance to dementia despite high Alzheimer disease pathology

D. Erten-Lyons, MD, R. L. Woltjer, MD, H. Dodge, PhD, R. Nixon, MD, R. Vorobik, BA, J. F. Calvert, MD, M. Leahy, RN, T. Montine, MD and J. Kaye, MD

From the Veterans Affairs Medical Center (D.E.-L., J.K.), Portland; Departments of Neurology (D.E.-L., R.L.W., H.D., R.V., J.K.), Family Medicine (J.F.C.,), and Pathology (R.L.W., R.N.), Oregon Health & Science University, Portland; Oregon State University (H.D.), College of Health and Human Sciences, Corvallis; University of Pittsburgh (H.D.), Graduate School of Public Health, PA; Merle West Center for Medical Research (J.F.C., M.L.), Klamath Falls, OR; and University of Washington (T.M.), Department of Pathology, Seattle.

Address correspondence and reprint requests to Dr. Deniz Erten-Lyons, Layton Aging and Alzheimer's Disease Center, 3181 SW Sam Jackson Park Road CR 131, Portland, OR 97239 ertenlyo{at}ohsu.edu

Background: Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms.

Methods: A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups.

Results: In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease.

Conclusion: Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

AD = Alzheimer disease; CDR = Clinical Dementia Rating Scale; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; CIRS = Cumulative Illness Rating Scale; ICV = intracranial volume; LB = Lewy bodies; MMSE = Mini-Mental State Examination; NCSE = Neurobehavioral Cognitive Status Examination; NFT = neurofibrillary tangle; NIA = National Institute on Aging; NP = neuritic plaques; OHSU = Oregon Health & Science University; Ref = reference; SES = socioeconomic status; UPDRS = Unified Parkinson's Disease Rating Scale.

Supplemental data at www.neurology.org

Supported by Merit Review Grant & Research Career Development Award, Office of Research and Development, Department of Veterans Affairs, National Institute on Aging, National Institutes of Health (AG08017, MO1 RR000334).

Disclosure: The authors report no disclosures.

Received May 30, 2008. Accepted in final form September 29, 2008.




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Correspondence:

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Factors associated with resistance to dementia despite high Alzheimer disease pathology
Majid Fotuhi, MD, PhD, et al.
Neurology Online, 21 May 2009 [Full text]
Reply from the authors
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