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#BrainHealth: delaying or preventing age-related cognitive impairment

Preserving the population's cognitive capital will reduce the burden of dementia on Society. #BrainHealth #HealthyAgeing

At the 2017 Association of British Neurologists (ABN) meeting in Liverpool, Professor Martin Rossor, in his ABN Medalist Lecture, made the point that at a population level we should be attempting to preserve Cognitive Capital. He was making a plea for public health officials to focus on ways to encourage the population to preserve their cognition, which in turn would help delay the onset of neurodegenerative diseases. This is exactly our thinking and what underpins the hypothesis that to reduce all-cause dementia we should be testing population level prevention strategies targeting simple things such as vascular comorbidities and lifestyle factors that are established risk factors for dementia, or are associated with the development of dementia.  

What are the chances of this strategy working for Alzheimer's disease (AD) the commonest cause of dementia? The study below shows that AD is frequently associated with small vessel disease. The hypothesis is therefore very simple; if you target small vessel disease you protect brain and cognitive reserve, which in turn protects you from getting dementia. This is easier said than done, but unless we try we won't know if we can delay or prevent the avalanche of dementia that threatens our society. From the perspective of the an individual this is also important as it will allow you to age more healthily and hence improve, or maintain, your quality of life. Viewed like this our proposed strategy is more about 'Healthy Ageing' than 'Dementia Prevention'. 

Arvanitakis et al. Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol. 2016 Aug;15(9):934-943.

BACKGROUND: Few data on the pathology of cerebral vessel disease, dementia, and cognition are available. We examined the association of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer's disease dementia and cognitive function.

METHODS: This cross-sectional study included men and women aged 65 years or older who had yearly clinical assessments and had agreed to brain autopsy at the time of death, as part of one of two cohort studies of ageing (The Religious Orders Study and the Rush Memory and Aging Project). Individuals without dementia or with Alzheimer's disease dementia, and with complete neuropathological data, are included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Clinical data recorded between 1994 and 2015 were used to determine presence of Alzheimer's disease dementia. Systematic neuropathological assessments documented the severity of cerebral large vessel (atherosclerosis) and small vessel (arteriolosclerosis) disease. By use of regression analyses adjusted for demographics, gross and microscopic infarcts, and Alzheimer's disease pathology, we examined associations of vessel disease severity (mild, moderate, and severe) with odds of probable and possible Alzheimer's diseasedementia and cognitive function.

FINDINGS: Study enrolment began in January, 1994, and two cohort studies are ongoing. 1143 individuals were included in our analyses (median age at death 88·8 years; 478 [42%] with Alzheimer's disease dementia). Moderate-to-severe atherosclerosis was present in 445 (39%) individuals, and arteriolosclerosis in 401 (35%) individuals. Each level increase in the severity of atherosclerosis or arteriolosclerosis was associated with significantly higher odds of Alzheimer's disease dementia (odds ratio [OR] for atherosclerosis 1·33, 95% CI 1·11-1·58; OR for arteriolosclerosis 1·20, 1·04-1·40). Atherosclerosis was associated with lower scores for global cognition (estimate -0·10 [SE 0·04], p=0·0096) and four cognitive domains (episodic memory -0·10 [0·04], p=0·017; semantic memory -0·11 [0·05], p=0·018; perceptual speed -0·14 [0·04], p=0·00080; and visuospatial abilities -0·13 [0·04], p=0·0080), but not working memory (-0·05 [0·04], p=0·21). Arteriolosclerosis was associated with lower scores for global cognition (estimate -0·10 [0·03], p=0·0015) and four domains (episodic memory -0·12 [0·04], p=0·00090; semantic memory -0·10 [0·04], p=0·013; working memory -0·07 [0·03], p=0·045; perceptual speed -0·12 [0·04], p=0·0012), and a non-significant association was noted for visuospatial abilities (-0·07 [0·03], p=0·052). Findings were unchanged in analyses controlling for the presence of APOE ε4 allele or vascular risk factors.

INTERPRETATION: Cerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer's disease dementia, and are also associated with low scores in most cognitive domains. Cerebral vessel pathology might be an under-recognised risk factor for Alzheimer's disease dementia.


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