Ken Nagata, Takashi Yamazaki and Daiki Takano
Epidemiological studies disclosed that there are common risk factors in Alzheimer’s disease (AD) and vascular dementia (VaD). Theycan be classified into 4 major categories: Demographic, genetic, vascular and comorbidity risk factors. The demographic risk factor includes gender, age, past history, years in educational and occupational attainment. Male gender is a risk for VaD and stroke, whereas female gender is known as a risk factor for AD. The genetic factors for VaD may include such familial VaD as CADASIL. ApoE? 4 are known to be the possible common genetic factor for both VaD and AD. The lifestyle risk factors turn out to be obesity, lack of physical activity, cigarette smoking, excessive alcohol intake, and certain psychosocial factors. The vascular risk factors encompass hypertension in midlife, hypotension in late life, diabetes mellitus, dyslipidemia, congestive heart failure, myocardial infarction, arrhythmia, and chronic kidney disease. It is suggested that effective management of these vascular risk factors may prevent onset of dementia and cognitive decline. Randomized placebocontrolled trials of antihypertensive drugs showed that antihypertensive therapy may reduce the risk of VaD as well as AD. Low cardiac output due to hypotension and/or congestive heart failure has been regarded as a risk factor for cognitive impairment and dementia especially in elderlypatients whose autoregulation of cerebral blood flow is impaired. Although further research is needed, those evidences may support a rationale for the efficacious management of vascular risk factors in the prevention of VaD as well as AD. Alzheimer disease (AD) and vascular cognitive impairment (VCI) are estimated to be the number one and two leading causes of irreversible cognitive impairment of late life, respectively. VCI is a relatively new nosological term that takes into account the spectrum of severity of cognitive impairment associated with vascular disease (eg, mild, moderate, and severe, or the full-blown state called vascular dementia); the underlying pathophysiological mechanism (eg, subcortical ischemic vascular disease, amyloid angiopathy, cortical infarction, etc.); and the potential for intervention and prevention based on the pathophysiological mechanism of the “brain-at-risk” stage. Because both AD and stroke show an exponential increase in frequency with age, AD and VCI may coexist as a mixed form of cognitive impairment or the existence of stroke may unmask or potentiate AD.4,5 It has been hypothesized that there may be a synergism between AD and stroke pathogenic mechanisms.6 Cerebral ischemia and amyloid may synergize to produce AD and vascular changes in the brain. Furthermore, an angiogenesis hypothesis has been proposed, which links the two pathophysiological processes. However, in a recently published neuropathological study, cerebral infarctions were shown to independently contribute to the likelihood of dementia but did not interact with AD pathology to increase the likelihood of dementia beyond their additive effect.
