Multi-modal Approaches May Reduce Alzheimer's Disease Risk

Optimizing lifestyle factors may significantly reduce Alzheimer's risk

Posted Feb 12, 2019

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This is the second post in a series on complementary and alternative treatments of dementia. The previous post examined the evidence for diet in reducing the risk of developing Alzheimer's disease. This post begins with a short review of the limitations of available pharmacologic treatments then reviews findings on multi-modal approaches aimed at reducing inflammation and metabolic risk factors known to increase risk of Alzheimer's disease, and optimizing lifestyle factors known to reduce risk.  

Limitations of pharmacologic treatments

Currently available pharmacologic treatments of AD work by inhibiting the enzyme that breaks down acetylcholine, increasing available levels of the neurotransmitter that is critical for learning and memory. Promising early results of studies on tacrine, the first commercially marketed acetylcholinesterase inhibitor, were offset by findings of significant hepatotoxicity. Second-generation acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are no more effective than tacrine but require less frequent dosing and have fewer associated safety issues. These concerns led to discontinuation of tacrine in 2013.

Other medications that have been investigated for possible cognitive-enhancing benefits in dementia include the monoamine oxidase inhibitors (MAOIs), estrogen replacement therapy (i.e., in cognitively impaired postmenopausal women), naloxone, and various neuropeptides, including vasopressin and somatostatin (Zandi et al., 2005). Promising novel Western biomedical treatments of Alzheimer’s disease currently being investigated in clinical trials include a vaccine that may immunize individuals against formation of amyloid beta, secretase inhibitors, anti-inflammatory agents, and statins (Herline 2018; Cao 2018). Results of studies on statins in dementia have been inconsistent. However, a 2018 meta-analysis of 31 studies that met inclusion criteria for size and rigor found that regular statin use is associated with significant reduction of risk of developing dementia (Zhang 2018).

Multi-modal interventions aimed at optimizing life-style factors

Positive findings of studies on a preventive role of diet in dementia are confounded by the fact that individuals with healthy dietary habits also engage in other behaviors that reduce Alzheimer’s risk, for example, by exercising regularly and moderating alcohol consumption (Barberger-Gateau, Letenneur, Deschamps, Peres, Dartigues, & Renaud, 2002). These findings have led to studies on interventions that optimize lifestyle factors with the goal of preventing Alzheimer’s disease or slowing its rate of progression.  

One third of Alzheimer’s disease cases are probably caused by modifiable lifestyle factors suggesting that multi-modal interventions addressing many factors may have important preventive benefits. Modifiable lifestyle factors include low education, hypertension, diabetes, obesity, smoking, sedentary lifestyle and depressed mood. Only one large multi-center study has investigated multi-modal interventions aimed at preventing Alzheimer’s disease in elderly at-risk individuals (Ngandu 2015). The authors found significant improvements in overall cognition, processing speed and executive functioning in the treatment group that were significantly greater than in the control group.

Recent case reports have been published of dramatic improvement in individuals diagnosed with early Alzheimer’s disease who adhere to multi-modal life style changes (Bredesen 2014) aimed at enhancing cognitive performance and reducing metabolic risk factors associated with inflammation. These findings show that, in at least some cases, symptoms of early Alzheimer’s disease can be reversed within 6 months after initiating a comprehensive lifestyle regimen (Bredesen 2014). The goal of this approach is to normalize multiple metabolic parameters related to inflammation in the body, thus interrupting the pathological processes that eventually lead to Alzheimer’s disease. The protocol, called metabolic enhancement for neurodegeneration (MEND), entails comprehensive laboratory screening that may include serologic studies of inflammatory markers, functional brain scans, genetic analysis of risk, and cognitive testing. Personalized lifestyle changes and nutritional strategies are subsequently recommended to correct underlying causal factors of cognitive decline identified in screening. Many individuals with early Alzheimer’s disease (including some individuals with the ApoE4 gene who are at very high risk of developing an early severe form of Alzheimer’s disease) who adhere to the MEND protocol report sustained improvement in cognitive performance for several years and no longer meet criteria for a diagnosis of Alzheimer’s disease. Large prospective controlled trials are needed to confirm these dramatic findings, elucidate the relative contributions of different lifestyle changes and metabolic factors to clinical improvement.

Bottom line

Most available pharmacologic treatments of Alzheimer’s disease are limited in efficacy however statins may significantly reduce risk. Preliminary research findings suggest that multi-modal interventions aimed at reducing inflammation including changes in diet, regular exercise, aggressive management of health problems such as hypertension and diabetes, and normalizing metabolic factors associated with increased Alzheimer’s risk, may significantly reduce the risk of developing Alzheimer’s disease, delay its onset or slow its rate of progression. Long-term prospective studies are needed to confirm these findings and elucidate the relative contributions of changes in specific lifestyle factors to reduced Alzheimer’s risk.

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