Nutritional status and structural brain changes in Alzheimer's disease: The NUDAD project

Kim

et al. 2023

Stroke

BACKGROUND: Previous observational studies reported that a lower serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with a higher burden of cerebral small vessel disease (cSVD). The causality of this association is uncertain, but it would be clinically important, given that 25(OH)D can be a target for intervention. We tried to examine the causal effect of 25(OH)D concentration on cSVD-related phenotypes using a Mendelian randomization approach. METHODS: Genetic instruments for each serum 25(OH)D concentration and cSVD-related phenotypes (lacunar stroke, white matter hyperintensity, cerebral microbleeds, and perivascular spaces) were derived from large-scale genome-wide association studies. We performed 2-sample Mendelian randomization analyses with multiple post hoc sensitivity analyses. A bidirectional Mendelian randomization approach was also used to explore the possibility of reverse causation. RESULTS: We failed to find any significant causal effect of 25(OH)D concentration on cSVD-related phenotypes (odds ratio [95% CI], 1.00 [0.87–1.16], 1.01 [0.96–1.07], 1.06 [0.85–1.33], 1.00 [0.97–1.03], 1.02 [0.99–1.04], 1.01 [0.99–1.04] for lacunar stroke, white matter hyperintensity, cerebral microbleeds, and white matter, basal ganglia, hippocampal perivascular spaces, respectively). These results were reproduced in the sensitivity analyses accounting for genetic pleiotropy. Conversely, when we examined the effects of cSVD phenotypes on 25(OH)D concentration, cerebral microbleeds were negatively associated with 25(OH)D concentration (0.94 [0.92–0.96]). CONCLUSIONS: Given the adequate statistical power (>0.8) of the analyses, our findings suggest that the previously reported association between 25(OH)D concentration and cSVD phenotypes might not be causal and partly attributed to reverse causation.

Section: Discussionsupporting

confidence: 52%

Causal Effect of the 25-Hydroxyvitamin D Concentration on Cerebral Small Vessel Disease: A Mendelian Randomization Study

Kim

et al. 2023

Stroke

Dement Neurocogn Disord

“…Furthermore, patients with low BMI correlated with structural alterations, including more advanced medial temporal atrophy and more microbleeds. 36 In contrast to people with low BMI, normal older adults with high BMI had a better cognitive function, a slow rate of cognitive decline, and a decreased risk of developing dementia. 5 8 37 Our finding suggested that a high BMI index is a predictor of cognitive function and good health status in late life, as evidenced by the “obesity paradox.”…”

Section: Discussionmentioning

confidence: 97%

Association Between Body Mass Index and Cognitive Function in Mild Cognitive Impairment Regardless of APOE ε4 Status

Mun

Park

Kim

et al. 2022

Background and Purpose In this study we aimed to find the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, we investigated the effects of the apolipoprotein E (APOE) genotype in the relationship between the BMI and cognition in MCI. Methods We enrolled a cohort of 3,038 subjects with MCI aged 65–90 from the Clinical Research Center for Dementia of South Korea and a dementia cohort of the Ewha Womans University Mokdong Hospital. MCI patients were classified into three subgroups according to the Asian standard of BMI. We compared cognitive performances between groups by one-way analysis of variance. To investigate the effects of the APOE genotype, we used multivariate linear regression models after adjusting for possible confounders. Results Even though normal BMI groups were younger, had more females, and had less comorbidities, the higher BMI groups had better cognitive functions. Among subjects with APOE ε4 carriers, there was a positive relationship between the BMI and the memory task alone. Conclusions Our findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE ε4 genotype in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype-specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.

“…Further, malnutrition often results in an immunosuppressive state, potentially leading to infection in the acute stroke period [ 28 ]. Malnutrition is also associated with an increased risk of white matter hyperintensities [ 29 ], microbleeds and mesial temporal lobe atrophy in the general population, and in patients with mild cognitive impairment or dementia [ 30 ]. Therefore, those with premorbid malnutrition may be more vulnerable to ischemic injury if they have an underlying amyloid-beta-related pathology or vascular burden.…”

Section: Discussionmentioning

confidence: 99%

Association between Geriatric Nutritional Risk Index and Post-Stroke Cognitive Outcomes

et al. 2021

Background: It is not yet clear whether nutritional status is associated with post-stroke cognitive impairment (PSCI). We examined the geriatric nutritional risk index (GNRI) on the domain-specific cognitive outcomes 3 months after a stroke. Methods: A total of 344 patients with acute ischemic stroke were included for the analysis. The GNRI was calculated as 1.489 × serum albumin (g/L) + 41.7 × admission weight (kg)/ideal body weight (kg) and was dichotomized according to the prespecified cut-off points for no risk and any risks. The primary outcome was PSCI, defined as having adjusted z-scores of less than −2 standard deviations in at least one cognitive domain: executive/activation, memory, visuospatial and language. Multiple logistic regression and linear regression analyses were performed to investigate the association between the GNRI and cognitive outcomes. Results: Seventy (20.3%) patients developed PSCI 3 months after a stroke. The mean GNRI was 106.1 ± 8.6, and 59 (17.2%) patients had low (<98) GNRI scores. A low GNRI was independently associated with the PSCI after adjusting for age, sex, education, initial stroke severity, stroke mechanism and left hemispheric lesion (odds ratio, 2.04; 95% confidence interval, 1.00–4.14). The GNRI scores were also significantly associated with the z-scores from the mini-mental status examination and the frontal domain (β = 0.04, p-value = 0.03; β = 0.03, p-value = 0.03, respectively). Conclusions: A low GNRI was independently associated with the development of PSCI at 3 months after an ischemic stroke. The GNRI scores were specifically associated with the z-scores of the global cognition and frontal domain cognitive outcomes.