Lipids, lipoproteins, and apolipoproteins: Associations with cognition and dementia

Due to increasing lifespan and aging populations globally there has been a steep rise in late-life dementia, which is now the second most common cause of death in high-income countries. In general, dementia can be divided into two major groups: Alzheimer's disease (AD) and vascular-related dementia (VD). AD is pathologically characterised by senile plaques containing amyloid-β and neurofibrillary tangles composed of hyperphosphorylated tau, whereas VD is dominated by vascular pathology such as cerebral small vessel disease, major strokes, and white matter lesions. Recently, the importance of vascular components in AD is increasingly recognized and it is estimated that up to 45 % of all dementia cases can be prevented by preventing or treating midlife cardiovascular risk factors such as physical inactivity, diabetes, and hypertension. Even though the brain contains approximately 25 % of the total body cholesterol pool, and several genetic variants related to the lipid metabolism have been identified in genome-wide associations studies of AD, the role of lipids, lipoproteins, and apolipoproteins in dementia risk is less well-known. In this review, we go through the current literature on lipids, lipoproteins, and apolipoproteins and risk of dementia. We conclude that the evidence is primarily insufficient or conflicting, possibly due to nonoptimal study designs. The future calls for large, prospective studies of midlife measurements of lipids, lipoproteins, and apolipoproteins and one-sample, individual level data Mendelian randomization studies to overcome survival bias. However, the current literature suggests that it is safe to say that what is good for the heart is good for the brain.