Title: Predementia and Dementia Syndromes: Possible Role of Lipoprotein Metabolism
Volume: 3
Issue: 3
Author(s): Francesco Panza, Anna Maria Colacicco, Alessia D'Introno, Cristiano Capurso, Angelo Del Parigi, Sabrina A. Capurso, Gaetano Gagliardi, Gianfranco Pichichero, Antonio Capurso and Vincenzo Solfrizzi
Affiliation:
Keywords:
Dementia, Alzheimer's disease, vascular dementia, mild cognitive impairment, apolipoprotein E, cholesterol, lipoprotein (a), amyloid β-protein
Abstract: An exciting area of research focuses on the relationship between vascular factors and Alzheimers disease (AD), suggesting vascular risk factors, including circulating factors such as serum/plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], and serum apolipoprotein E (APOE) levels, as a key part of late-onset AD pathology. However, the link between the lipoprotein metabolism and dementia or predementia syndrome appears to be unclear and controversial. This review will focus on current knowledge on circulating serum and plasma risk factors for cognitive decline of degenerative (AD) or vascular origin (VaD) linked to TC homeostasis and lipoprotein disturbances, i.e. TC, 24S-hydroxy-cholesterol, Lp(a) or APOE. These measures linked to lipoprotein metabolism appear to be altered in AD, VaD, or predementia syndromes relative to controls, but with contrasting results. The prevailing view is that high TC is a risk factor for dementia. Nevertheless, the relationship between TC and dementia may vary considerably depending on when TC is measured over the life course or, alternatively, in relation to the underlying course of the disease. Moreover, studies assessing the role of statins, which are effective in lowering cholesterol, gave inconclusive results in reducing the risk of dementia. The evaluation of APOE serum levels and APOE genotype in AD patients suggested that serum APOE levels could not be a credible risk factor or a biochemical marker for AD. In fact, there is no consistent association of serum or plasma APOE protein levels with diagnosis when controlled for APOE genotype. In addition, there is evidence that higher Lp(a) levels could be linked with AD, although there are studies suggesting an increased presence of low molecular weight apo(a) isoforms in AD, VaD, and frontotemporal dementia, that genetically determined elevated Lp(a) levels. Furthermore, although serum/plasma levels of TC and 24S-hydroxycholesterol are not credible diagnostic markers for AD and cognitive decline, current evidence suggests they may be modifiable risk/protective factors. Thus, more studies with long-term follow-up and serial assessments of TC are needed to further clarify the causal relationship between cholesterol and dementia.
