WML, strokes, and dementia increase with increasing age. WML show levels of heritability, are common in the elderly even when asymptomatic and are not the benign finding they were once thought to be. For a review see Hsu-Ko. WML or hyperintensities are related to increased cardiovascular risk and a reduction in cerebral blood flow, cerebral reactivity, and vascular density although it is unclear if the WML prompt the vessel loss or vice versa. They may also associated with further tissue changes in grey matter visible when using magnetisation transfer magnetic resonance imaging. WML are found more in frontal rather than posterior brain regions in keeping with cognitive and morphological findings discussed above) and the fact that WML are related to poor cognition has been shown. Other damage associated with ageing and related to blood pressure and vascular factors include strokes and small vessel disease. Moderate to high 24 hour ambulatory blood pressure has been related to increased brain atrophy as has increased variability of systolic blood www.postgradmedj.com pressure. In Japanese subjects raised systolic blood pressure was related to grey matter volume loss in a cross sectional study and in the Framingham offspring cohort an increased 10 year risk of first stroke was associated with decrements in cognitive function. The authors suggest that this may be attributable to cerebrovascular related injuries, accelerated atrophy, white matter abnormalities, or asymptomatic infarcts. That cerebral vasculature could be related to cognitive function is not surprising because microvasculature ability to respond to metabolic demand falls with increasing age and moreover functional adult neurogenesis may be related to good capilliary growth. For reviews see Lie et al and Riddle et al. In addition to this there have been many links made between dementia, even AD, and vascular risk factors.

Increasing evidence points to vascular factors not only contributing to cognitive problems in ageing but also to the two most common dementias seen in this population. The prevalence of dementia increases almost exponentially with increasing age with around 20% of those aged 80 affected rising to 40% of those aged 90.

The dementia types seen most frequently in the elderly are AD accounting for around 40%–70% of dementias, and vascular dementia (VaD) 15%–30%. In recent years, it has seemed increasingly likely that there is an overlap between these two dementias and there have been calls for AD to be reclassified as a vascular disorder or for dementia to become a multifactorial disorder A postmortem study found that 77% of VaD cases showed AD pathology and high blood pressure has been associated with increased neurofibrilliary tangles characteristic of AD. Multiple types of vascular pathology have been associated with AD includ- ing microvascular degeneration, disorders of the blood-brain barrier, WML, microinfarctions, and cerebral haemorrhages. It has been suggested that large vessel factors, for example, atherosclerosis, increase the risk of AD and may play a part in cerebral vessel amyloid deposition. AD patients do show significantly higher levels of cerebrovascular pathology when compared with controls at postmortem examination although this did not correlate with severity of cognitive decline. A similar finding, that small infarcts in AD do not affect the rate of cognitive decline, suggests that vascular factors may unmask or magnify underlying AD pathology, or shorten the pre-clinical phase of AD, at least in Western populations. Alternatively multiple risk factors may be acting together. The characteristic neurofibrilliary tangles and plaques found in AD are also evident to some degree in most elderly brains at postmortem examination even those without symptoms, as are white matter lesions. The issue of normal ageing is a difficult one because thereare studies that show cognitively intact adults aged 100, and yet a high percentage suffer from dementia and the line between mild cognitive impairment and normal memory changesis still a little blurred. What is in no doubt is that changes in brain vasculature, WML and intra/extra cellular changes are likely to begin in midlife. There are many influences on the ageing brain, genetics, biological, and environmental influences all of which contribute to the physiological and cognitive changes; Mattson provided a review.

Risk factors that have been put forward with regard to,ageing and development of dementia include hypertension, diabetes, hyperhomocysteinaemia, and a high cholesterol although the evidence for all but hypertension is far from clear. Protective factors include diet, alcohol, exercise, and intellectual pursuits.


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