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P1‐090: Dementia in advanced aging: A manifestation of many different brain diseases
Author(s) -
Nelson Peter,
Neltner Janna
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.366
Subject(s) - neuropathology , medicine , pathological , prodrome , disease , dementia , autopsy , hippocampal sclerosis , cognitive impairment , brain aging , pathology , gerontology , psychiatry , psychosis , temporal lobe , epilepsy
Background: Correlation between Alzheimer’s disease (AD) neuropathology and cognitive impairment is not simplistic. Like most chronic diseases, there is an expected prodrome phase (i.e., preclinical disease) and imperfect clinical-pathological correlation at autopsy. Cognitive impairment in advanced aging is the norm although the brains of many aged individuals lack appreciable AD pathology. Two key non-AD brain pathologies are cerebrovascular disease (CVD) and hippocampal sclerosis (HS-Aging). Rubrics are still evolving for clinical-pathological correlation in these brain diseases.Methods:We assessed large autopsy series including the National Alzheimer’s Coordinating Center (NACC) Registry, the University of Kentucky AD Center, the Nun Study, and the Georgia Centenarian Study. Each of these data sources has highly textured clinical data (patients were followed longitudinally) and quantitative neuropathological metrics. Results: CVD pathology is practically ubiquitous in extreme old age. The clinical impact of CVD although difficult to predict confidently for any individual patient – is correlated with systematic changes in pathological outcomes. Persons with CVD tend to have lower AD-related pathology with a given degree of cognitive impairment. Correspondingly, as people become older (with more CVD), a larger percentage of AD patients die with more moderate AD pathology-Braak stage V rather than Braak stage VI. We are also increasingly impressed by the prevalence and impact of HS-Aging. Based on data from the largest series of HS-Aging cases to date, it seems as though prior low estimates of HS-Aging prevalence were partially biased by inclusion of younger patients. The average age at death for HS-Aging in this large cohort was over 90 years. In this group, each year after age 95 brought higher risk for HS-Aging pathology, but lower risk for AD pathology. Since HS-Aging shares a key biomarker with AD (shrunken hippocampi on MRI), there is likely to be clinical diagnostic uncertainty in some cases. Conclusions: CVD and HS-Aging neuropathology from large autopsy cohorts provides key insights of direct relevance to Alzheimerologists: some high-morbidity brain diseases, unlike AD, peak in extreme old age.