Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort

Abstract

Background Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due to limitations of these studies. Objectives To examine the prospective relation between total and 6 classes of dietary flavonoid intake and risk of ADRD and Alzheimer disease (AD) while addressing limitations of earlier observational studies. Methods We used data from the Framingham Heart Study Offspring Cohort exams 5 through 9. Participants were ADRD-free with a valid FFQ at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average intake across the 5 exams, and were expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to handle their nonlinear relation with ADRD and AD. Cox proportional hazards regression was used to estimate the HRs for the association between the flavonoid intakes and incidence of ADRD and AD. Results Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, individuals with the highest (>60th percentile) intakes of flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD relative to individuals with the lowest intakes (≤15th percentile), with HRs (95% CI; P-trend) of 0.54 (0.32, 0.90; P = 0.003) for flavonols, 0.24 (0.15, 0.39; P < 0.001) for anthocyanins, and 0.58 (0.35, 0.94; P = 0.03) for flavonoid polymers. The same pattern of associations was seen with AD for flavonols and anthocyanins but not for flavonoid polymers. Conclusions Our findings imply that higher long-term dietary intakes of flavonoids are associated with lower risks of ADRD and AD in US adults.

Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

“…Additionally, the incidence of stroke was reduced with increased dietary flavonol intake [33]. Data on neurodegenerative disorders are also encouraging [34,35]. The results by Shishtar et al suggest that higher long-term consumption of flavonoids in the diet lowers the risk of Alzheimer's disease development in adults [34].…”

“…Data on neurodegenerative disorders are also encouraging [34,35]. The results by Shishtar et al suggest that higher long-term consumption of flavonoids in the diet lowers the risk of Alzheimer's disease development in adults [34]. Parkinson's disease progression in men is also less likely with higher dietary flavonoid consumption [36].…”

Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?

“…In addition, berries, such as blueberry and grape, have shown potential to prevent neurodegeneration and cognitive decline [ 82 , 83 , 88 , 89 , 90 , 91 , 92 ]. Recent studies emphasize the association between higher dietary flavonoid intake and a lower incidence of AD dementia [ 93 , 94 ]. In contrast, a recent meta-analysis investigating a series of health endpoints found no significant association between polyphenol intake and cognitive ratings, such as the AD Assessment Scale–Cognitive Subscale (ADAS-Cog) [ 95 ].…”

Flavonoids mitigate neurodegeneration in aged Caenorhabditis elegans by mitochondrial uncoupling

“…Further, flavonoids may protect neuronal cells from some of the adverse effects of aging‐associated diseases and neurodegenerative diseases (Spencer, 2007; Youdim & Joseph, 2001). Regular intake of flavonoid‐rich foods showed decreased risk of dementia, Alzheimer's disease, and Parkinson's disease (Commenges et al., 2000; Gao et al., 2012; Shishtar et al., 2020). The antioxidant activity of flavonoids is considered to be a prominent mechanism in reducing the severity of aging‐associated diseases since many of the neurological disorders, diabetes, and vascular defects can be exacerbated or caused by free radicals (Pandey & Rizvi, 2009).…”