Current prevalence estimates for late-onset Alzheimer’s disease LOAD in the United States (U.S.) is approximately 5.1 million.(1) By 2050 the projected prevalence of LOAD is expected to escalate to 13.8 million and a staggering 106.8 million worldwide.(2,3) Pharmacological treatments for LOAD such as cholinesterase inhibitors and NMDA receptor antagonists may slow its progression or attenuate specific molecular pathomechanisms associated with the disease process, but are not long term solutions or curative. While there is active research for more effective disease-modifying drugs* the lack of any significant breakthroughs in the treatment of the disease has propelled a paradigm shift away from focusing solely on a pharmaceutical solution to an inclusive prevention model that emphasizes risk reduction and ultimately the portentous global burden incurred by the disease.
Several clinical trials have recently explored the potential role of prevention-based interventions for decreasing the risk of late-onset Alzheimer’s disease (LOAD) and vascular dementia. The outcomes are encouraging. Multi-dimensional interventional strategies (implementing multiple treatment and prevention modalities simultaneously) versus mono-therapy (employing only with a single treatment modality e.g. drugs) has yielded promising results in reducing the eventual onset of dementia for aging individuals considered to be at higher risk. These trials highlight the potential effectiveness of preventive approaches for individuals deemed to have a higher risk for vascular dementia and LOAD and for the management of Mild Cognitive Impairment (MCI).**
By Ralph Sanchez, MTCM, CNS, D.Hom.
Recently (11/13), a rare variant of the TREM2 gene, designated as R47H, was shown to increase the risk of developing Alzheimer’s disease. Individuals with the variant may be up to 3 to 5 times more likely to develop Late Onset Alzheimer’s disease (LOAD). This susceptibility to LOAD in R47H genotypes, is similar to that conferred by the ApoE4 gene.
The TREM2 gene is involved in immune regulatory processes in the brain and the R47H mutation impairs the gene’s ability to contain inflammation. One of the roles of the TREM2 gene is to aid the brain in efficiently eliminating beta amyloid; the toxic protein that forms plaques associated with Alzheimer’s disease.
Genetic risk factors to Late Onset Alzheimer’s Disease (LOAD) are significant. A recent study of nearly 12,000 Swedish twin pairs, age 65 and older, determined that 58% to 79% of Alzheimer’s risk is genetic (1). This study showed that in male identical twins, when one brother had Alzheimer’s disease, the other developed the disease 45% of the time. In female identical twins, when one sister had Alzheimer’s disease, the other developed the disease 60% of the time. While this study did not delve into specific gene influences in LOAD, numerous studies have identified Apolipoprotein E4 (ApoE4), as a prominent genetic risk factor for LOAD. About 25% of the population has one copy of the ApoE4 gene and individuals with the the ApoE4 gene are estimated to make up approximately 40%-80% of the Alzheimer’s disease population. (2)