Epidemiological Neuropathology: The MRC Cognitive Function and Aging Study Experience

Abstract

We here describe the study-design major findings from the neuropathological component of the Medical Research Council Cognitive Function and Aging Study (MRC CFAS). MRC CFAS is a population-representative study of aging and health including more than 18000 participants at baseline. More than 500 brain donations were accrued to date and have been subjected to comprehensive pathological assessment. This resource enables a thorough epidemiological description of the neuropathology associated with dementia in the UK. Results to date reveal a high prevalence of mixed Alzheimer and vascular pathology, a significant population who die with dementia but with a more limited pathological burden than is traditionally associated with dementia, and a group who die with a significant pathological burden yet remained cognitively intact until death. This dissociation between pathology and dementia increases with increasing age. Further studies have described the distribution and etiology of neurodegenerative disease in the population, and determined pathological correlates of cognitive impairment and dementia. Brain donation programs linked to epidemiological studies provide an invaluable resource for describing the pathological correlates of dementia in a way that is representative of the population, thereby identifying targets for and assessing the likely effect of therapeutic and preventive interventions.

Strictly Lobar Microbleeds Are Associated With Executive Impairment in Patients With Ischemic Stroke or Transient Ischemic Attack

“…29 Community-based pathological studies, including the Honolulu-Asia Aging Study and MRC Cognitive Function and Aging Study, found CAA to be associated with cognition even after controlling for age and neurodegenerative pathology. 28,30 The Religious Orders Study showed that moderate-to-severe CAA was linked to impairment in specific cognitive domains, particularly perceptual speed, assessed with the Symbol Digit Modalities Tests and Number Comparison tests 31 ; however, we found no association between CMBs and speed and attention functions, also assessed by the Symbol Digit Modalities test. Possible explanations include the following: first, our patients all attended hospital with ischemic stroke or TIA, whereas the Religious Orders Study included community-based subjects, in whom only 36% had cerebral infarction at autopsy; and second, the Religious Orders Study found associations with moderate-to-severe CAA pathology, whereas our patients with strictly lobar CMBs probably have less severe CAA pathology.…”

Mesial Temporal Astrocyte Tau Pathology in the MRC-CFAS Ageing Brain Cohort

“…The study details have been described in detail elsewhere [11][12][13][14]. Assessment of dementia in the study was based on a standardised assessment for psychiatric disorders in older people (GMS AGECAT).…”

Epidemiological findings of vascular risk factors in Alzheimer’s disease: implications for therapeutic and preventive intervention

“…Population-based autopsy studies show that brain infarctions and severe intracranial atherosclerosis increase the odds of dementia independent of AD pathologies [109][110][111][112], suggesting that intracranial atherosclerosis and microvascular pathologies play a part in the development of the dementia syndrome. Indeed, intracranial atherosclerosis and AD may share common pathogenic mechanisms, such as oxidative stress, inflammation and toxic b-amyloid.…”