Vascular Risk Factors and Neurodegeneration in Ageing Related Dementias: Alzheimer’s Disease and Vascular Dementia

Rufus   O.   Akinyemi; Elizabeta   B.   Mukaetova-Ladinska; Johannes      Attems; Masafumi      Ihara; Raj   N.   Kalaria

Abstract

Age is the strongest risk factor for brain degeneration whether it results from vascular or neurodegenerative mechanisms or both. To evaluate the current views on the impact of vascular disease on the most common causes of dementia, most relevant articles to the selected subject headings were reviewed until November 2011 from the popularly used databases including Pubmed, Cochrane Database and Biological Abstracts. Within the past decade, there has been four-fold increased interest in the vascular basis of neurodegeneration and dementia. Vascular ageing involving arterial stiffness, endothelial changes and blood-brain barrier dysfunction affects neuronal survival by impairing several intracellular protective mechanisms leading to chronic hypoperfusion. Modifiable risk factors such as hypertension, diabetes, dyslipidaemia and adiposity linked to Alzheimer’s disease and vascular dementia promote the degeneration and reduce the regenerative capacity of the vascular system. These in tandem with accumulation of abnormal proteins such as amyloid β likely disrupt cerebral autoregulation, neurovascular coupling and perfusion of the deeper structures to variable degrees to produce white matter changes and selective brain atrophy. Brain pathological changes may be further modified by genetic factors such as the apoliopoprotein E ε4 allele. Lifestyle measures that maintain or improve vascular health including consumption of healthy diets, moderate use of alcohol and implementing regular physical exercise in general appear effective for reducing dementia risk. Interventions that improve vascular function are important to sustain cognitive status even during ageing whereas preventative measures that reduce risk of vascular disease are predicted to lessen the burden of dementia in the long-term.

Keywords: Ageing, Alzheimer´s disease, cerebral blood flow, dementia, diabetes, diet, physical actvity, stroke, vascular dementia, white matter lesions.