Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature.
Nelson, Peter T. MD, PhD; Alafuzoff, Irina MD, PhD; Bigio, Eileen H. MD; Bouras, Constantin MD; Braak, Heiko MD; Cairns, Nigel J. PhD, FRCPath; Castellani, Rudolph J. MD; Crain, Barbara J. MD, PhD; Davies, Peter PhD; Tredici, Kelly Del MD, PhD; Duyckaerts, Charles MD, PhD; Frosch, Matthew P. MD, PhD; Haroutunian, Vahram PhD; Hof, Patrick R. MD; Hulette, Christine M. MD; Hyman, Bradley T. MD, PhD; Iwatsubo, Takeshi MD; Jellinger, Kurt A. MD; Jicha, Gregory A. MD, PhD; Kovari, Eniko MD; Kukull, Walter A. PhD; Leverenz, James B. MD; Love, Seth MBBCH, PhD; Mackenzie, Ian R. MD; Mann, David M. PhD, FRCPath; Masliah, Eliezer MD; McKee, Ann C. MD; Montine, Thomas J. MD, PhD; Morris, John C. MD; Schneider, Julie A. MD, MS; Sonnen, Joshua A. MD; Thal, Dietmar R. MD; Trojanowski, John Q. MD, PhD; Troncoso, Juan C. MD; Wisniewski, Thomas MD; Woltjer, Randall L. MD, PhD; Beach, Thomas G. MD, PhD
Journal of Neuropathology & Experimental Neurology.
71(5):362-381, May 2012.
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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. [beta]-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 forunderstanding 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 A[beta] plaques and neurofibrillary tangles. Although A[beta] plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
(C) 2012 American Association of Neuropathologists, Inc