Introduction
Alzheimer’s disease (AD) is a progressive, multifactorial, neurodegenerative disease generally characterized by personality changes, memory loss, and a decline in overall cognitive function. The significant genetic risk factor for AD is the apolipoprotein E, epsilon 4 allele (ApoE4), and the inheritance of one or two copies of ApoEε4 increases AD risk approximately 3- or 12-fold, respectively. Based on recent findings, it seems that ApoE4 acts as a transcriptional factor and binds to the promoters of genes involved in a range of processes linked to AD disease pathogenesis. While the development of effective treatment and prevention is a significant healthcare goal, unfortunately, therapeutic approaches to AD to date have not led to sustainable improvements. Based on recent evidence from several independent groups, it seems that AD is unique to each individual, and different individuals have different genetics, epigenetics, biochemistry, subtypes, and thus different responses to treatment.
Figure 1. Identifying and addressing potential contributors to cognitive decline with a personalized, multi-therapeutic approach is supportive of cognitive health. Shown in the figure are the various core strategies for the reversal of AD and MCI and for optimizing brain health. Adapted from source.
Multiple Strategies to Optimize Brain Health
Diet and Nutrition
A healthy dietary management method including dietary patterns, food, and dietary supplements may be a component of an effective protocol to prevent AD-associated cognitive impairment. Since the gut microbiome and gastrointestinal (GI) issues, metabolic syndromes, like diabetes and obesity, gut inflammation, and oxidative stress have been evaluated to play a major role in cognitive impairment and AD. The Mediterranean, DASH (Dietary Approaches to Stop Hypertension), and MIND ( Mediterranean-DASH Intervention for Neurodegenerative Delay) diets encompass a multi-nutrient dietary profile that includes fruits, vegetables, nuts, cereals, olive oil, legumes, and a low to moderate intake of dairy products.
The DASH diet also emphasizes foods that are low in sodium and rich in potassium, calcium, and magnesium. Higher adherence to these diets was associated with better cognitive function, lower rates of cognitive decline, and a reduced risk of AD. Specific nutrients like unsaturated fatty acids, antioxidants, and dietary flavonoids have also been associated with better cognitive functioning and a lower risk of cognitive decline in the follow-up period.
Physical Exercise
Physical exercise has been proven to help prevent and remediate cognitive decline. Research studies have indicated that a consistent practice of physical activity is associated with a lower risk of cardiovascular disease, and physically active people are less likely to develop dementia. Specifically, three types of exercise are suggested for brain health:
- Aerobic exercise increases heart rate and oxygen uptake, thereby improving cardiovascular health, which in turn benefits the brain. Studies have indicated that aerobic exercise improves blood flow to the brain and stimulates the release of brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity thereby preserving brain volume.
- Strength training physical exercises enhance muscle strength, muscle mass, and endurance thereby preventing sarcopenia. Also, strength training exercises improve higher-level cognitive processes and memory, stabilize brain volume, and decrease white matter lesions.
- Mind-body exercise combined with body movement improves balance, gait, coordination, and agility; improves the synaptic, neuronal, and vascular systems of the brain.
A multifactorial intervention involving diet, physical exercise, and other lifestyle changes may be more effective for alleviating cognitive decline and may have a sustained beneficial effect that is more pronounced than a single intervention.
Sleep
The core function of sleep is to repair, reorganize, maintain brain health, and clear waste. Usually, sleep disturbances will occur in the preclinical phase of AD. Cognitive decline and an increased risk of mild cognitive impairment and dementia are associated with poor sleep quality. Poor sleep triggers β-amyloid build-up in the brain regions including the thalamus and hippocampus, which are vulnerable to damage in the early stages of AD. AD may be accompanied by other comorbid medical conditions which can contribute to sleep issues. Melatonin is a sleep-influencing, circadian-rhythm-dependent neuroendocrine hormone that has a protective role in the development of AD because of its anti-inflammatory and antioxidant effects.
Mind and Mental Exercise
AD is characterized by altered hippocampal synaptic efficacy leading to synaptic dysfunction, neuronal degeneration, and cognitive impairment. One of the most important sensory activities is the sense of sound, which has the power to stimulate the brain, which is why hearing loss has a profound effect on brain health. Recent studies indicate that hearing loss causes brain changes that raise the risk for AD. Results from several observational studies have demonstrated that people who engage in cognitively stimulating activities may show improvement in moods, thinking, hearing, problem-solving, memory, and reasoning.
Stress Management
Studies have indicated that stress is one of the key factors involved in the development of AD. Stress management methods for people with AD that are effective in improving subjective well-being include mindfulness techniques, breathing exercises, meditation, yoga, spiritual practice, socialization, and other activities that focus on the present moment. Also, music therapy and art improve the quality of life and cognitive and emotional functions.
Toxins
Toxins are increasingly identified to raise the risk of AD. Specific toxins that can lead to dementia are called dementogens and include metals, organic chemicals, and biotoxins. Mercury, aluminum, lead, arsenic, and cadmium are associated with numerous heart issues, even at low levels of exposure. Chronic exposure to chemical toxins like pesticides, industrial chemicals, and air pollutants triggers a reduction in volumes of the hippocampus and total gray matter.
Conclusion
Alzheimer’s disease is now the fifth leading cause of death for adults and the most common cause of dementia among older adults. Diet, sleep, physical activity, stress, and environment all contribute to the progression of the disease and therefore multi-factorial optimization of the network support and function offers a rational therapeutic strategy. While each of these strategies has been shown to reverse cognitive decline and promote neuroplasticity when practiced together, their combined effect may be additive or even synergistic and the advantages may be sustained, leading to overall health optimization and improved cognition.