Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

By Peter T. Nelson, I. Alafuzoff, Eileen Bigio, C. Bouras, H. Braak, Nigel J. Cairns, Rudolph Castellani, B. Crain, P. Davies, K. Del Tredici and 27 more. Journal of Neuropathology and Experimental Neurology, 2012

1,882 citations recorded by the source corpus.

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. &bgr;-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&bgr; plaques and neurofibrillary tangles. Although A&bgr; plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.

Subfields: Physiology, Psychiatry and Mental health, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/bce678baa6d56ad7c06197507d7903b6c7619507

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Citations in the corpus

Alzheimer’s disease: experimental models and reality (2017, background): “There have been many clinicopathological studies that have correlated amyloid plaques with cognitive deficits in AD, with an emerging picture that the strongest correlation exists in the earliest stages of the disease and this association greatly weakens as NFTs and neocortical degeneration become m”
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. (2016, background): “…has a devastating effect on synaptic function (Gomez-Isla et al., 1997; Beharry et al., 2014; Spires-Jones and Hyman, 2014) and relates more strongly to cognitive functions during life than does amyloid-b (Arriagada et al., 1992; Nelson et al., 2012; van Rossum et al., 2012; Rolstad et al., 2013).”
Inflammation as a central mechanism in Alzheimer's disease (2018, background): “[38] Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ,”
Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease (2017, background): “In contrast, amyloid-b pathology has only a relatively modest direct correlation with cognition (Nelson et al., 2012).”
Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014, background): “First, the strongest correlation between amyloid plaques and cognition is in the early stages of the disease and this association weakens as NFTs and gross neocortical neurodegeneration become more widespread (Thal et al., 2002; Nelson et al., 2009b, 2012).”
PET Imaging of Tau Deposition in the Aging Human Brain (2016, neutral): “…participants according to Braak stage, we also found, consistent with previous findings (Braak and Braak, 1991, 1997; Braak et al., 2006, 2011; Nelson et al., 2012; Serrano-Pozo et al., 2011), increasing Braak stage in cognitively healthy and diseased participants to be associated with…”
Primary age-related tauopathy (PART): a common pathology associated with human aging (2014, background): “This criterion is supported by extensive genetic and clinicopathologic observations [108].”
Tau PET imaging in aging and early Alzheimer’s disease (2015, background): “We observed a significant relationship between age and inferior temporal (18)F T807 binding within the relatively restricted age range of our normal participants, consistent with large autopsy studies.(2) Studies of (18)F T807 PET in younger subjects will be required to test whether entorhinal corte”
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, positive): “For example, there is minimal correlation between phases of amyloid deposition and degree of cognitive decline (Nelson et al., 2012).”
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “These tissue changes precede the onset of clinical signs by several years, implying that AD neuropathological lesions may be found in a subset of cognitively normal elderly persons (130).”