title: Alzheimer and vascular neuropathological changes associated with different cognitive States in a non-demented sample.
abstract: The state between aging with no cognitive impairment and dementia has become a major focus for intervention. The neuropathological and neurobiological correlates of this intermediate state are therefore of considerable interest, particularly from population representative samples. Here we investigate the neuropathological profile associated with different cognitive ability levels measured using strata defined by Mini Mental State Examination (MMSE) scores. One hundred and fifty one individuals were stratified into three cognitive groups including: non-, mildly, and moderately impaired at death. Alzheimer's disease, atrophy, and vascular pathologies were investigated. Mild impairment was associated with an increased risk of vascular pathologies including small vessel disease and lacunes. In contrast, the moderately impaired group showed a more extensive pattern of pathology, including tangles and neuritic plaques (entorhinal/hippocampus), atrophy (cortical and hippocampal), and vascular disease (small vessel disease, lacunes, and infarcts). In a population-based sample of older people, MMSE score defined strata are associated with multiple pathologies. The profile of AD and vascular changes becomes more complex with increased cognitive impairment and these changes are likely to constitute a major substrate for age associated cognitive impairment. The results highlight the need for rigorous investigation of both neurodegenerative and vascular risks factors in old age.
authors.affiliation: Department of Public Health and Primary Care, Institute of Public Health, Cambridge, UK. bcms2@cam.ac.uk
authors.forename: Blossom C M
authors.initials: BC
authors.lastname: Stephan
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Matthews
authors.forename: Brandy
authors.initials: B
authors.lastname: Ma
authors.forename: Graciela
authors.initials: G
authors.lastname: Muniz
authors.forename: Sally
authors.initials: S
authors.lastname: Hunter
authors.forename: Daniel
authors.initials: D
authors.lastname: Davis
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
authors.forename: Gill
authors.initials: G
authors.lastname: Foster
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ince
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology*; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000145:classification / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology*