Neuropathologic features associated with Alzheimer disease diagnosis

Abstract

Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods:We conducted a cross-sectional analysis of 2,014 older adults (Ն70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made Յ1 year before death, n ϭ 419) or AD (at Ն65 years, n ϭ 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: Conclusion:Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. Neurology Age is arguably the strongest risk factor for dementia.1 Those 85 years or older, referred to as the oldest old, accounted for less than 1% of the population in 1996 but comprised approximately 40% of dementia cases.2,3 Despite high prevalence of dementia among the oldest old, cognitive impairment in this age group is not well characterized by symptoms or neuropathology, 4 with relatively few neuropathologic studies of Alzheimer disease (AD) in the oldest old. [5][6][7][8][9][10][11][12][13][14][15] Preliminary studies that compared the strength of association between dementia diagnosis or cognitive performance and AD neuropathology (neuritic plaques and neurofibrillary tangles) between the young old and the oldest old suggest that the association is weaker among the oldest old 6,13 ; however, these studies were limited by small to moderate size and considered

Diagnostic Accuracy of Statistical Pattern Recognition of Electroencephalogram Registration in Evaluation of Cognitive Impairment and Dementia

“…The authors, however, only used one dimension of the method (NRM vs. AD), when in reality the patients had different causes The clinical diagnosis of AD does not correlate very well with neuropathology, not least in the oldest individuals [37]. This is most probably the reason a minor fraction of those diagnosed with AD have EEG features of normal individuals as seen in figure 1.…”

“…Even though the MCI patients were followed for at least 2 years, the other clinical groups were diagnosed cross-sectionally and therefore mistakes in diagnosis cannot be ruled out. The methods used in the diagnostic work-up are similar to those used in most other memory clinics, it is likely that the proportion of incorrect diagnoses is of a similar magnitude as in other clinics or 5-15% [37].…”

Challenges in the Neuropathological Diagnosis of Dementias

“…In a prospective study of 180 demented patients (mean age 85±3.4 years), autopsy showed AD in 48%, AD with vascular pathology in 19%, VaD in 11%, DLB in 9%, and dementia of unknown etiology in 13% (Jellinger and Attems, 2010), confirming the notion that a high percentage of demented persons aged 80+ do not met the pathological criteria of AD or were classified as "dementia of unknown etiology" (Crystal et al, 2000;Jellinger, 2001). Non-AD pathology significantly improved precise differentiation between oldest-old and younger age groups (Middleton et al, 2011). …”

“…Increased densities of neuritic plaques and NFTs are absent in non-demented patients over age 85-90 (Polvikoski et al, 2006;Prohovnik et al, 2006;Haroutunian et al, 2008;Nelson et al, 2009;Middleton et al, 2011;Jellinger and Attems, 2012), and there is considerable overlap in the pathologies found in demented and non-demented patients (Fernando and Ince, 2004). On the other hand, by age 80-85 years, many cognitively unimpaired subjects may have substantial cortical AD pathology (JL Price et al, 2009), while others found significant positive correlation between the extent of dementia and senile plaque density (p=0.011), but not for the NFT density score (p=0.076) .…”

Neuropathology of Dementia Disorders

“…A 90+ study revealed significantly less severe Aβ, αSyn and TP'D-43 pathologies and hippocampal lesions in non-demented subjects, while Aβ distribution showed no esssential differences; non-demented individuals had limited hippocampal tau and neocortical Aβ pathology [241]. Non-AD pathology significantly improved precise differentiation between oldest-old and younger age groups [263]. …”