title: Correlation of Alzheimer disease neuropathologic changes with cognitive status:  a review of the literature.
abstract: Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
authors.affiliation: Sanders-Brown Center on Aging, Department of Pathology, University of Kentucky, Lexington 40536-0230, USA. pnels2@email.uky.edu
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.forename: Constantin
authors.initials: C
authors.lastname: Bouras
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Rudolph J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Crain
authors.forename: Peter
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authors.lastname: Davies
authors.forename: Kelly
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authors.lastname: Del Tredici
authors.forename: Charles
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authors.lastname: Duyckaerts
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Vahram
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authors.lastname: Haroutunian
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hulette
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jellinger
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.forename: Enikö
authors.initials: E
authors.lastname: Kövari
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: David M
authors.initials: DM
authors.lastname: Mann
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sonnen
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.forename: Randall L
authors.initials: RL
authors.lastname: Woltjer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D006801:Humans; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D013223:Statistics as Topic
chemical_list: D016229:Amyloid beta-Peptides