So Yeon Kim

Background: Numerous studies have demonstrated an association between altered liver function and Alzheimer’s disease (AD) or related dementia. Nevertheless, the neuropathological substrates underlying the association remains unclear. Our aim was to investigate the association between liver function markers and the longitudinal changes of in vivo AD pathologies.Methods: We utilized a longitudinal study designs using data from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease, an ongoing prospective cohort study that began in 2014. Total 347 older adults between 55 and 90 years of age assessed at both baseline and 2‐year follow‐up were included in community and memory clinic setting. We used four liver function markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], AST to ALT ratio, and total bilirubin) as exposure variables. Participants underwent comprehensive clinical assessments and multimodal brain imaging, including Pittsburgh compound‐B positron emission tomography (PET), AV‐1451 PET, fluorodeoxyglucose (FDG)‐PET, and MRI at both baseline and the 2‐year follow‐up.Results: A higher ALT level and lower AST to ALT ratio at baseline were associated with greater amyloid deposition over a 2‐year period (ALT: β, 0.151 [95% CI, 0.007 to 0.033], P = 0.004; AST to ALT ratio: β, ‐0.153 [95% CI, ‐0.050 to ‐0.010], P = 0.004), but not with the change of other neuroimaging markers. A lower total bilirubin level was associated with greater tau deposition over a 2‐year period (β, ‐0.442 [95% CI, ‐0.385 to ‐0.106], P < 0.001), but not with the change of other neuroimaging markers. In contrast, AST alone was not associated with any neuroimaging marker change.Conclusions: The present findings, based on longitudinal observation for older adults, suggest that lower liver function may accelerate the accumulation of AD pathology in the brain. These results also support the possibility that the liver‐brain axis could be a potential target for therapeutic or preventive strategies against AD.

Background: This study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer’s disease (AD) assessment battery.Methods: The study included 196 nondemented adults aged 65 to 90 years at a university hospital and community. Comprehensive clinical assessments including the 30-item Geriatric Depression Scale (GDS) to measure components of depressive symptoms, TS, and blood nutritional biomarkers.Results: Our stepwise logistic regression analysis highlighted the ‘helplessness item’ (odds ratio = 4.531, 95% CI = 2.218 to 9.258, p < 0.001) as a significant predictor for MCI diagnosis. Further, models incorporating ‘helplessness item + MMSE’ demonstrated markedly enhanced accuracy in diagnosing MCI, surpassing the performance of the MMSE used independently. Notably, the group characterized by helplessness showed a significant reduction in TS (B = −5.300, SE = 1.899, β = −0.162, p = 0.006), with this trend being particularly pronounced in individuals exhibiting lower levels of physical activity. Interestingly, this correlation did not manifest in participants with higher physical activity levels.Conclusion: Our findings suggest that helplessness is highly effective in diagnosing MCI and is linked to a decrease in cognitive function. Therefore, when addressing MCI and AD-related cognitive decline, clinicians should consider helplessness.

Background: Despite the known associations between zinc levels and Alzheimer’s disease (AD) dementia and related cognitive impairment, the underlying neuropathological links remain poorly understood. We tested the hypothesis that serum zinc level is associated with cerebral beta-amyloid protein (Aβ) deposition. Additionally, we explored associations between serum zinc levels and other AD pathologies [i.e., tau deposition and AD-signature cerebral glucose metabolism (AD-CM)] and white matter hyperintensities (WMHs), which are measures of cerebrovascular injury. Methods: A total of 241 cognitively normal older adults between 55 and 90 years of age were enrolled. All the participants underwent comprehensive clinical assessments, serum zinc level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Zinc levels were stratified into three categories: < 80 μg/dL (low), 80 to 90 μg/dL (medium), and > 90 μg/dL (high). Results: A low serum zinc level was significantly associated with increased Aβ retention. In addition, apolipoprotein E ε4 allele (APOE4) status moderated the association: the relationship between low zinc level and Aβ retention was significant only in APOE4 carriers. Although a low zinc level appeared to reduce AD-CM, the relationship became insignificant on sensitivity analysis including only individuals with no nutritional deficiency. The serum zinc level was associated with neither tau deposition nor the WMH volume. Conclusions: Our findings suggest that decreased serum zinc levels are associated with elevation of brain amyloid deposition. In terms of AD prevention, more attention needs to be paid to the role of zinc.

Young Min Choe, So Yeon Kim, Ihn-Geun Choi, Guk-Hee Suh, Dong Young Lee, Boung Chul Lee, Jee Wook Kim. Clin Psychopharmacol Neurosci 2020;18:627-30. https://doi.org/10.9758/cpn.2020.18.4.627