Neuropathology of Cognitively Normal Elderly

Abstract

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.

Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia

“…Neuropathologically, control cases had low burden of Alzheimer's pathology: all have Braak scores ≤3 and CERAD score B or less (only one case had C) ( Table 1). These data are in agreement with published results regarding Alzheimer's pathology in cognitively intact elderly [56]. Of 21 PD cases, 8 (38%) had no additional clinical diagnosis, whereas 13 (62%) were additionally diagnosed with dementia.…”

Very low levels of education and cognitive reserve

“…1 Approximately 30% of cognitively normal subjects have intermediate-to high-likelihood AD pathology at autopsy. [2][3][4][5][6][7] According to this theory, subjects with greater cognitive reserve require a more severe neuropathologic burden to reach the threshold for clinical dementia. 8 Previous clinicopathologic studies suggest that although education is not directly related to the development of neuropathologic lesions, it appears to reduce the impact of such lesions on the development of dementia, thereby increasing cognitive reserve.…”

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

“…The five stable isotope labeled internal standards were well separated chromatographically at the following retention times: 8-[8- Three replicate analyses were performed to determine the dynamic range of each stable isotope labeled internal standard. Positive significant correlations were observed between the instrument response over a range of 500 pmol to 100 nmol for: 8 30 min at 4°C. The supernatant (PBS-soluble pool) was collected and the remaining pellet sonicated (10×0.5 sec pulses at 100 W) in 2% (w/v) SDS with PIC and centrifuged at 20,800×g for 30 min at 14°C.…”

“…Subjects with mild cognitive impairment (MCI) experience a perceived and verifiable change in cognition but are not demented and maintain functional independence antemortem [2][3][4] and postmortem exhibit AD associated pathology but to a lesser extent than demented AD subjects [5]. More recently postmortem analyses have described the presence of senile plaques (SP) and neurofibrillary tangles (NFT) in the brains of cognitively normal subjects suggestive of an extended 'preclinical AD' (PCAD) stage of AD in which extensive pathology exists in the absence of obvious clinical manifestations [6][7][8][9].…”