Alzheimer Disease Pathology in Subjects Without Dementia in 2 Studies of Aging: The Nun Study and the Adult Changes in Thought Study

• Published in: Journal of neuropathology and experimental neurology Vol. 70; no. 10; pp. 832 - 840
• Main Authors: SantaCruz, Karen S., Sonnen, Joshua A., Pezhouh, Maryam Kherad, Desrosiers, Mark F., Nelson, Peter T., Tyas, Suzanne L.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.10.2011; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Aged; Aged, 80 and over; Aging - pathology; Alzheimer Disease - complications; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Apolipoproteins E - genetics; Biological and medical sciences; Brain - pathology; Cognition & reasoning; Cognition Disorders - etiology; Cognition Disorders - pathology; Cognitive ability; Data collection; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia - complications; Dementia - epidemiology; Dementia - pathology; Disease; Female; Humans; Lewy Bodies - pathology; Longitudinal Studies; Male; Medical sciences; Metabolic disorders; Neurofibrillary Tangles - pathology; Neurology; Neuropsychological Tests; Pathology; Retrospective Studies; Statistics, Nonparametric; Studies; Human; Nervous system diseases; Senescence; Nun Study; Alzheimer disease; Central nervous system; Adult Changes in Thought study; Brain reserve; Asymptomatic; Cerebral disorder; Encephalon; Presymptomatic; Anatomic pathology; Central nervous system disease; Degenerative disease; Preclinical; Dementia
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1097/NEN.0b013e31822e8ae9

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.