Editorial: Lifestyle and Environmental Influences on Alzheimer's Disease

Pei Shang^1*Ruogu Cheng²Guohao Wang^3*Song Qiao⁴Hongquan Wang⁵YAN LIU⁶Zhengjun Wang⁷

• ¹Mayo Clinic, Rochester, United States
• ²Southern Medical University Nanfang Hospital, Guangzhou, China
• ³National Institutes of Health, Islamabad, Pakistan
• ⁴Zhejiang Hospital, Hangzhou, China
• ⁵Aerospace Center Hospital, Beijing, China
• ⁶Lanzhou University, Lanzhou, China
• ⁷The University of Tennessee Health Science Center, Memphis, United States

AD has become the most rapidly increasing neurodegenerative disorder in the world, imposing a huge burden on both families and society. So far, the available treatment modalities for AD are still constrained. Previous research has demonstrated that conventional pharmacological agents, including cholinesterase inhibitors and NMDA receptor channel antagonists, can enhance the clinical manifestations of AD and mitigate its progression (1,2). Nevertheless, these therapeutic interventions can not provide a cure for AD, exhibit minimal effect on the underlying pathological function of the disease, and thus present challenges in managing the long-term progression of AD (3). Furthermore, although the FDA has recently approved monoclonal antibodies aimed at β -amyloid for the treatment of early symptomatic AD, the current experience with anti-β -amyloid disease-modifying therapies (DMTs) is still limited. Consequently, further research is essential to evaluate both the clinical efficacy and the economic implications of these therapies.Mild cognitive impairment (MCI) associated with AD represents an intermediary phase between cognitive health and the onset of AD (4). This stage serves as a " window period " for early diagnosis and prevention of AD. Neurobiologically, it is marked by reduced blood flow and metabolic activity in the temporoparietal cortex, atrophy of the medial temporal lobes-especially in the nasal cortexelevated Tau protein levels in cerebrospinal fluid (CSF), diminished phosphorylation and A β 42 levels, as well as the deposition of A β 42 in the brain. Clinical manifestations of MCI include symptoms of depression as well as the utilization of avoidance coping strategies (5). Delaying the progression of MCI to AD will effectively reduce the incidence of AD and result in substantial savings in medication expenses. This has prompted an examination of the influence of risk factors, such as lifestyle and environmental elements, on the progression of AD, as well as efforts to mitigate the risk of AD through multifaceted intervention strategies. In addition, it has a notable advantage that cannot be ignored compared to other drug therapies, as it is non-toxic and does not cause any negative side effects.Advanced age has been widely recognized as the most important risk factor for the development of AD. At the same time, the other twelve modifiable factors, including cardiovascular health and poor dietary patterns, have been gradually demonstrated to be associated with an increased risk of AD. The combined rate of these potential risks of AD due to these factors is at a significant number of 40% in the whole world, suggesting that intervention with these pre-adjusted risk factors is crucial for the prevention of AD (6).Despite this, there are few empirical studies on the use of non-pharmacological interventions for the prevention and treatment of AD worldwide. In this Research Topic, we focused on describing the lifestyle and environmental influences on AD, especially exploring the roles of diet, exercise, cognitive reserve, sleep, and air quality. A total of nineteen articles on this topic have been published, primarily summarizing the potential impact of the intervention of lifestyle and environment on the progression of AD. Recent research has illuminated the intricate interplay between lifestyle and environmental factors in modulating AD risk and progression. Diet, particularly adherence to the Mediterranean diet, significantly reduces cardiovascular-related mortality among cognitively impaired individuals, suggesting a potential protective role in AD pathways (7,8). Exercise is repeatedly shown to bolster cognitive resilience, with a frequency of ≥3 times/week offering optimal benefits. Notably, combining physical activity with natural neuroprotective compounds, such as platycodin D, has synergistic effects in reducing amyloid burden and inflammation in AD mouse models (9).Cognitive reserve (CR), shaped by education and possibly enhanced by brain clearance systems like the glymphatic pathway, emerges as another critical factor (10). Higher education independently correlates with a reduced risk of cognitive impairment, and glymphatic activity appears to mediate CR's benefits on cognition. Tools like nomograms incorporating CR, age, and genetic predispositions also show promise for early identification of MCI (11).Sleep duration interacts with metabolic health to influence cognitive outcomes, especially in overweight and obese older adults, where a sleep window of 5-6 hours may be neuroprotective (12). Similarly, environmental exposures such as secondhand smoke (SHS) and pollutants like acrolein have been implicated in accelerating cognitive decline, particularly when combined with other vulnerabilities like vitamin D deficiency (13). Acrolein's role in promoting oxidative stress and amyloid-beta toxicity underscores the impact of air quality on AD pathology (14).Moreover, rural living and neighborhood disadvantage have been associated with distinct neuroanatomical changes, pointing to broader socioeconomic and environmental contributors to AD risk (15). Additional insights highlight that metabolic factors such as high BMI and elevated cardiac metabolic index (CMI) are biomarkers of accelerated aging and potential contributors to AD (16).Finally, entertainment-based cognitive activity, such as computer use, shows a modest but significant protective association, reinforcing the value of sustained mental engagement (17). As dementia continues to impose a significant global burden, this growing body of evidence emphasizes the multifactorial nature of AD and supports comprehensive prevention strategies targeting modifiable lifestyle and environmental factors (18)(19)(20).In summary, based on our topic manuscripts, we propose that clinicians should be aware that AD can be prevented, and the progression of this incurable disease may be delayed through the modification of assorted risk factors, although the causal relationship between these non-pharmacological interventions and the progression of AD still needs to be confirmed in large-scale studies and national reports.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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