Table 1 Risk factors for vascular dementia (VaD)

Demographic

Advanced age

Accounts for many unrecognized vascular changes in the brain. After the age of 65, the risk of developing dementia increases gradually [60]

Sex/gender

Inconclusive findings

Some studies report that males are overall at a higher risk till the age of 85 and the overall prevalence of VaD becomes higher in women than in men, especially at very old age (> 85)

Other studies argue that the protective effects of estrogen in women against coronary heart disease account for a lower risk of VaD in females [60, 94, 98, 251]

Education

Data is inconclusive but there are studies that report an association between a low formal education with a greater risk of developing VaD [239, 246]

Social class

Occupational classes such as professional/Intermediate, skilled non-manual, skilled manual and part-skilled/unskilled have shown to be associated with dementia risk. The higher the class, the lower the dementia risks [225, 253]

Genetic factors

No robust genetic risk factors have been identified. However, APOE and NOTCH3 mutations can be associated with the formation of VCI as these individuals may be predisposed to strokes and other CVD that can potentially manifest as VaD [54, 98, 131, 262, 281]

Lifestyle Factors

Smoking

Smoking and tobacco addiction has been identified as significant risk factors for cardiovascular disease, cerebral vascular disease and cognitive decline. Particularly, smoking causes vascular endothelial dysfunction and atherosclerotic damage [8, 17, 97]

Cognitive reserve

Cognitive reserve explains the theory that some individuals have a structurally and functionally more resilient brain against injury and disease. This risk factor may be associated with external influences such as education and occupation [69, 225]

Alcohol use

Heavy drinking or chronic harmful use of alcohol is associated with other vascular risk factors such as high blood pressure, stroke, atrial fibrillation and CHD. Moderate drinking has mostly shown to have beneficial effects, although some studies report structural brain damage [236, 270, 284]

Diet

Effective individual nutrients such as vitamins E and B can provide for neuroprotective benefits in the brain. Some foods such as saturated fats and trans fats have been shown to increase cognitive decline and hence increase the risk for developing dementia [186,187,188]

Physical inactivity

Intervention studies of physical activities on cognition have revealed that indeed the risk of dementia decreases with increased activity. However, there is still insufficient data to confirm this association because increased physical activities complement other risk factors such as risk of obesity and stroke [1, 58]

Homocysteine

Hyperhomocysteinemia has been shown in studies to be associated with vascular disease. Homocysteine induces cellular damage via oxidative stress, excitotoxicity, and damage to the blood–brain barrier. Studies have also shown an association between high levels of Homocysteine and increased risk of atherosclerosis, atrophy and white matter diseases [3, 109, 211, 256, 274]

Chronic disorders

Stroke

A person with the history of stroke becomes approximately three to nine times as likely to develop VaD as compared to a healthy individual. Furthermore, the risk of VaD increases further in patients who already are suffering from pre-stroke cognitive decline [61, 117, 153, 164, 208]

CAD/CHD/ischemic heart disease

CAD/CHD/Ischemic Heart Disease has been identified to be a significant independent risk factor for vascular dementia and risk of cognitive decline. Atherosclerosis plays a major role in the development of CAD/CHD and has been observed clinically in many VaD patients [90, 101, 137, 154, 193, 202, 219]

PAD/PVD

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis in the body and has been reported to increase the risk of dementia types such as AD and VaD by double. This is especially apparent in patients with severe peripheral vascular disease (PVD) and ischemic heart disease. In fact, PAD was associated with a faster cognitive decline independently of previous CVD risk factors [205, 212, 267]

Atrial fibrillation

This form of cardiac arrhythmia has been shown to be a significant independent risk factor for vascular dementia and AD. Moreover, patients with underlying microvascular dysfunction in addition to AF may manifest VaD earlier [36, 137]

Hypertension

High blood pressure is not just a risk factor for dementia, but for other conditions such as stroke as well. In fact, many studies have reported that hypertension is an independent risk factor for VaD [137, 190, 303]

Diabetes mellitus

Studies have reported associations between diabetes and developing early-stage cognitive impairment and also in VaD. Diabetes is also strongly associated with cerebral Vasculopathy. It has been reported that the risk of developing VaD is higher when diabetes occurs at the mid-life stage rather than the late-life stage as other environmental factors provide for a stronger link at the later life stage [111, 137, 204, 216, 302]

Myocardial infarction

Patients with MI have a higher risk of developing cognitive impairment due to brain hypoperfusion. It has been reported that women with MI are five times more likely to develop cognitive impairment as compared to men. An effect of MI is low cardiac output, promotes brain hypoperfusion and hence is associated with cognitive decline and manifestation into dementia [13, 30, 66, 137, 316]

Hypercholesterolemia

High cholesterol is one of the risk factors for VaD. Hypercholesterolemia has been shows to be one of the dominant mechanisms in atherosclerosis and hence cognitive decline [9, 66, 75, 209]

Depression

Although inconclusive, there are studies that report mid- and late- life depression is associated with a higher risk of VaD. Particularly, depression that only begins at the late- life stage is associated with AD, but recurring depression is associated with VaD [21, 37]

Overweight/obese

Obesity decreases blood supply to the brain and fat cells damage the cerebral white matter leading to cognitive decline and hence VaD. Damaged white matter decreases neuronal functioning and eventual brain atrophy. The mechanism for obesity-induced damage is the obesity-induced release of adipocyte-secreted proteins and obesity-induced inflammatory cytokine release [7, 12, 148]