Summary:
Lifestyle factors, including diet, physical activity, stress, and social engagement, are increasingly recognized as influencing the risk and progression of dementia, including Alzheimer’s disease (AD). Studies also indicate that diets rich in vegetables and omega-3 fatty acids are associated with reduced AD risk, while high intake of saturated and trans fats increases risk. Given the multifactorial nature of AD, interventions targeting multiple lifestyle domains such as diet, exercise, cognitive stimulation, and heart health, may be more effective than single interventions. This paper reported a 20-week randomized controlled trial investigating whether an intensive multimodal lifestyle intervention could influence progression in patients already diagnosed with mild cognitive impairment (MCI) or early AD. The intervention included a whole-food, plant-dominant diet low in refined sugars and harmful fats with selected supplements, moderate exercise, stress management, and support groups. Primary outcomes were changes in cognition, and secondary outcomes included changes in cognitive measures or biomarkers. Fifty-one participants completed the study. After 20 weeks, the intervention group showed significant improvements in overall clinical impression of change, daily functional abilities, and global clinical dementia ratings, with borderline improvement in a standard cognitive test assessing memory, attention, and problem-solving. The control group declined across all measures. Levels of plasma Aβ42/40, a biomarker associated with Alzheimer’s disease, positively increased in the intervention group, while they decreased in the control group. These changes correlated with adherence to the lifestyle program. Gut microbiome composition also improved significantly in the intervention group. These findings suggest that comprehensive lifestyle modifications can improve cognition and function and may slow or reverse progression in patients with MCI or early AD.
Abstract:
Background: Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD. Methods: A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures. Results: Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p= 0.001), CDR-SB (p= 0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group (p <0.0001). Conclusions: Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD.
Article Publication Date: 07/06/2024
DOI: 10.1186/s13195-024-01482-z
