Mechanisms Underlying Non-Pharmacological Dementia Prevention Strategies: A Translational Perspective

Abstract

Since developing an effective treatment for Alzheimer’s disease (AD) has been encountered as a challenging task, attempts to prevent cognitive decline by lifestyle modifications have become increasingly appealing. Physical exercise, healthy diet, and cognitive training are all modifiable, non-pharmacological lifestyle factors considered to influence cognitive health. Implementing lifestyle modifications on animal models of AD and cognitive impairment may reveal underlying mechanisms of action by which healthy lifestyle contribute to brain health. In mice, different types of lifestyle interventions have been shown to improve cognitive abilities, alleviate AD-related pathology and neuroinflammation, restore mitochondrial function, and have a positive impact on neurogenesis and cell survival. Different proteins and pathways have been identified to mediate some of the responses, amongst them BDNF, Akt–GSK3β, JNK, and ROCK pathway. Although some important pathways have been identified as mediating improvements in brain health, more research is needed to confirm these mechanisms of action and to improve the understanding of their interplay. Moreover, multidomain lifestyle interventions targeting multiple risk factors simultaneously may be a promising avenue in future dementia prevention strategies. Therefore, future work is needed to better understand the synergistic impact of combinatory lifestyle strategies on cellular mechanisms and brain health.

Multidomain interventions for risk reduction and prevention of cognitive decline and dementia: current developments

“…Alanko et al [42 ▪ ] provided a summary of mechanisms of nonpharmacological mainly Alzheimer's disease prevention studies in mice. Indeed, lifestyle interventions in mice have been shown to reduce Alzheimer's disease-related disorder and neuroinflammation and to benefit mitochondrial function, neurogenesis, and cell survival.…”

The Role of Intermittent Fasting and Dieting on Cognition in Adult Population: A Systematic Review of the Randomized Controlled Trials

“…Similarly, the Mediterranean diet involves the consumption of fruits, vegetables, whole grains, olive oil, fish, nuts, and legumes and low consumption of processed foods, dairy, and red meat [1] . The Mediterranean diet has shown slowing of neurodegenerative processes including oxidative stress and neuroinflammation which have been associated with improvement in cognitive function, lower rates of cognitive decline, and a reduced risk of Alzheimer’s disease [4] . When both DASH and Mediterranean diets were compared, there were similar rates of slowing cognitive decline in adults [4] .…”

“…The Mediterranean diet has shown slowing of neurodegenerative processes including oxidative stress and neuroinflammation which have been associated with improvement in cognitive function, lower rates of cognitive decline, and a reduced risk of Alzheimer’s disease [4] . When both DASH and Mediterranean diets were compared, there were similar rates of slowing cognitive decline in adults [4] . The Mediterranean diet has shown a stronger association with positive cognitive outcomes compared to other specific food groups due to the cumulative beneficial effects of individual ingredients in the diet [5] .…”

The Molecular Effects of Environmental Enrichment on Alzheimer’s Disease

“…Regardless, these initial studies were essential as they laid the foundation for EE as a potential therapy to combat neurodegenerative diseases. Throughout the past decade, many reviews have highlighted the effectiveness of EE against AD pathogenesis [ 31 , 32 , 33 , 34 , 35 , 36 ]. Most notably, it has been shown that EE reversed Aβ pathology as well as reduced senile plaque aggregation in transgenic AD mice [ 37 , 38 ].…”