Neuropathological Findings in the Very Old: Results from the First 101 Brains of a Population‐based Longitudinal Study of Dementing Disorders

Abstract

We report a unique longitudinal epidemiological study of cognitive decline in the elderly population of the city of Cambridge, UK. A population sample of people aged 75 and over was surveyed between 1984-1996 (n = 2,616) and followed 2.4, 6, and 9 years later. CAMDEX diagnostic criteria were used for clinical assessment, and the neuropathological protocol (in 101 cases) was based on the CERAD method, with additional features to allow Braak staging of neurofibrillary pathology. The main findings are of the heterogeneity of lesions to be found in very old populations, and the existence of considerable overlap in the pathologies found in the demented and nondemented. It seems that white matter (ischemic) pallor an amyloid angiopathy, as well as neuritic plaques, neurofibrillary tangles and Lewy body formation are all lesions that increase the likelihood of dementia.

Prevalence and Pathology of Dementia with Lewy Bodies in the Oldest Old: A Comparison with Other Dementing Disorders

“…Cerebrovascular pathology may also contribute to cognitive impairment in the elderly, and its impact on dementia has repeatedly been reported [2,3,7,10,11,12,17,18,19,23,24,33,73], but studies on the prevalence of CVL in DLB are scarce and contradictory. They were not considered in the San Diego study of oldest-old DLB patients [39].…”

“…Although established estimates of dementia in general and particularly in oldest-old people are crucial for public health planning, many epidemiologic studies must be interpreted cautiously due to referral biases, confounding effects of their comparison because of a lack of common diagnostic criteria, small numbers of very old individuals in most studies [3,9,10,11,12], and the fact that aged subjects with and without dementia show a high frequency of mixed pathologies and comorbidities [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]. In several autopsy series, the prevalence of dementing disorders varied considerably – AD and vascular dementia (VaD) ranging between 12 and 67% and 4.5 and 46.8%, respectively, mixed dementia (definite AD with severe vascular encephalopathy) between 2 and 86% (!)…”

Cerebral Microinfarcts: A Systematic Review of Neuropathological Studies

“…The greater part (63%) concerned hospital-based cohorts, mostly patients admitted to geriatric hospitals or dementia clinics. Twelve studies (41%) described a population-based cohort (Arvanitakis et al, 2011;Ballard et al, 2000;Rossi et al, 2004;Brayne et al, 2009; Review on cerebral microinfarcts M Brundel et al Xuereb et al, 2000;White et al, 2002;Sonnen et al, 2007;Schneider et al, 2007a, b;Strozyk et al, 2010;Troncoso et al, 2008;White, 2009;Wang et al, 2009), mostly of elderly, that is, the ACT Study (Sonnen et al, 2007;Wang et al, 2009) or the Baltimore Longitudinal Study on Aging (Troncoso et al, 2008). Two of these population-based studies involved specific groups of individuals: that is, only men (HAAS) (White et al, 2002;White, 2009) or people from religious orders (Religious Orders Study (Arvanitakis et al, 2011)) ( Table 1).…”

“…The most commonly used neuropathological criteria for AD were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (Mirra et al, 1991) and the Braak criteria (Braak and Braak, 1991). Fifteen studies (41%) primarily classified the patients on clinical criteria (Erkinjuntti et al, 1988;Vinters et al, 2000;Xuereb et al, 2000;White et al, 2002;Gold et al, 2007;Sonnen et al, 2007;Schneider et al, 2007a, b;Strozyk et al, 2010;Troncoso et al, 2008;White, 2009;Wang et al, 2009;Brayne et al, 2009;Ghebremedhin et al, 2010;Sinka et al, 2010;Arvanitakis et al, 2011). The Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2000) was used most frequently, followed by the Cognitive Assessment Screening Instrument (Teng et al, 1994).…”

Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons

“…Although several studies suggest a link between CAA and dementia, 3-7 findings come mainly from highly selected samples, and AD and other common age-related neuropathologies have infrequently been considered. [8][9][10][11] Furthermore, little is known about the relation of CAA with cognitive decline. We previously reported associations between CAA, perceptual speed, and episodic memory proximate to death in a sample a third the size of that in this study, 12 but studies examining the relation of CAA with the rate of change in multiple cognitive systems over time are rare.…”