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Review
. 2010 Dec;68 Suppl 2(Suppl 2):S74-87.
doi: 10.1111/j.1753-4887.2010.00352.x.

Vascular basis for brain degeneration: faltering controls and risk factors for dementia

Raj N Kalaria  1
Affiliations
Review

Vascular basis for brain degeneration: faltering controls and risk factors for dementia

Raj N Kalaria. Nutr Rev. 2010 Dec.

Abstract

The integrity of the vascular system is essential for the efficient functioning of the brain. Aging-related structural and functional disturbances in the macro- or microcirculation of the brain make it vulnerable to cognitive dysfunction, leading to brain degeneration and dementing illness. Several faltering controls, including impairment in autoregulation, neurovascular coupling, blood-brain barrier leakage, decreased cerebrospinal fluid, and reduced vascular tone, appear to be responsible for varying degrees of neurodegeneration in old age. There is ample evidence to indicate vascular risk factors are also linked to neurodegenerative processes preceding cognitive decline and dementia. The strongest risk factor for brain degeneration, whether it results from vascular or neurodegenerative mechanisms or both, is age. However, several modifiable risks such as cardiovascular disease, hypertension, dyslipidemia, diabetes, and obesity enhance the rate of cognitive decline and increase the risk of Alzheimer's disease in particular. The ultimate accumulation of brain pathological lesions may be modified by genetic influences, such as the apolipoprotein E ε4 allele and the environment. Lifestyle measures that maintain or improve cardiovascular health, including consumption of healthy diets, moderate use of alcohol, and implementation of regular physical exercise are important factors for brain protection.

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Figures

Figure 1
Figure 1
Schematic diagram showing various interfaces/barriers between blood or fluid and brain. Each of the sites can be affected to variable degree by ageing and more selectively as a consequence of neurodegenration. Abbreviations: AE: astrocytic endfoot, BM: basement membrane, EC: endothelial cell, P: pericyte, VSMC: vascular smooth muscle cell, FB: fibroblast, CSF: cerebrospinal fluid, Arach: arachnoid, SAS: subarachnoid space. Modified after Nils-Olof Hagnelius, 2009 (RNK, personal communication).
Figure 2
Figure 2
Hypothetical scheme showing the consequences of vascular disease risk clustering factors leading to brain degeneration and dementias. The general pathway may be modified by host influences including genetic, environmental or even perinatal influences. Abbreviations: Aβ, amyloid beta; AD, Alzheimer’s disease, APP, amyloid precursor protein; PSD, post-stroke dementia, VaD, vascular dementia; VCI, vascular cognitive impairment.
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