Findings from previous studies reporting the levels of serum brain-derived neurotrophic factor (BDNF) in patients with Alzheimer’s disease (AD) and individuals with mild cognitive impairment (MCI) have been conflicting. Hence, we performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls. Fifteen studies were included for the comparison between AD and healthy control (HC) (n = 2067). Serum BDNF levels were significantly lower in patients with AD (SMD: −0.282; 95% confidence interval [CI]: −0.535 to −0.028; significant heterogeneity: I2 = 83.962). Meta-regression identified age (p < 0.001) and MMSE scores (p < 0.001) to be the significant moderators that could explain the heterogeneity in findings in these studies. Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, n = 906) and between MCI and HC (nine studies, n = 5090). In all, patients with AD, but not MCI, have significantly lower serum BDNF levels compared to healthy controls. This meta-analysis confirmed the direction of change in serum BDNF levels in dementia. This finding suggests that a significant change in peripheral BDNF levels can only be detected at the late stage of the dementia spectrum. Molecular mechanisms, implications on interventional trials, and future directions for studies examining BDNF in dementia were discussed.

Few randomized controlled trials investigated the effects of mindfulness intervention on older adults diagnosed with mild cognitive impairment (MCI). Furthermore, there have been hypotheses and theoretical mechanisms on the benefits of mindfulness intervention on biomarkers of stress, inflammation, and neuroplasticity implicated in MCI that warrant empirical evidence. We conducted a pilot randomized controlled trial to examine whether Mindful Awareness Practice (MAP) improved biomarker levels in older adults with MCI. Fifty-five community-dwelling older adults aged 60 and above were randomized into either the treatment arm, MAP, or the active control arm, the health education program (HEP). Researchers who were blinded to treatment allocation assessed the outcomes at baseline, 3-month, and 9-month follow-ups. Linear-mixed models were used to examine the effect of MAP on biomarker levels. MAP participants had significantly decreased high-sensitivity c-reactive protein (hs-CRP) levels at 9-month (β = −0.307, 95% CI = −0.559 to −0.054 P = 0.018). Exploratory sub-group analyses by sex showed significantly decreased hs-CRP in females only (β = −0.445, 95% CI = −0.700 to −0.189, P = 0.001), while stratification by MCI subtype showed hs-CRP decreased only in amnestic-MCI (aMCI) (β = −0.569, 95% CI = −1.000 to −0.133, P = 0.012). Although total sample analyses were not significant, males had significantly decreased interleukin (IL)−6 (β = −1.001, 95% CI = −1.761 to −0253, P = 0.011) and IL-1β (β = −0.607, 95% CI = −1.116 to −0.100, P = 0.021) levels at 3-month and non-significant improvements at 9-month time-point. MAP improved inflammatory biomarkers in sex- and MCI subtype-specific manners. These preliminary findings suggest the potential of mindfulness intervention as a self-directed and low-cost preventive intervention in improving pathophysiology implicated in MCI.

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Introduction The projected growth of Alzheimer's disease (AD) and AD‐related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. Methods In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. Results Bronfenbrenner defined the “macrosystem” as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. Discussion Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. Highlights Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro‐level determinants have been understudied in the AD/ADRD literature.