1. Investigación

Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are currently unknown. The answer could lie on the involvement of gastrointestinal factors, such as adipokines (e.g., leptin, adiponectin, and resistin) and ghrelin. In this context, we conducted a pre-registered systematic review and meta-analysis of 42 cross-sectional and 13 longitudinal studies targeting the associations between leptin, adiponectin, resistin, and ghrelin and the prevalence of general dementia, AD, and mild cognitive impairment (MCI). We also examined the relationship between the four gastrointestinal factors and neurocognitive outcomes and AD-related cerebrospinal fluid biomarkers. Patients with AD had lower blood leptin and higher resistin levels than cognitively normal participants. Lower leptin and higher resistin were associated with higher degree of cognitive impairment. Additionally, lower late-life leptin levels might be associated with higher prospective risk of dementia and AD, although more studies are needed to corroborate this. Results in ghrelin and adiponectin were not conclusive, with age, sex distribution, obesity, and severity of dementia seemingly acting as moderators across several analyses. Our work might contribute to the identification of new preclinical blood markers of MCI and AD.

Obesity has become a major public and individual health problem due to its high worldwide prevalence and its relation with comorbid conditions. According to previous studies, obesity is related to an increased risk of cognitive impairment and dementia. This systematic review aims to further examine the present state of the art about the association between obesity and gray matter volume (GMV) as assessed by magnetic resonance imaging (MRI). A search was conducted in Pubmed, SCOPUS and Cochrane of those studies released before 1 February 2021 including MRIs to assess the GMVs in obese participants. From this search, 1420 results were obtained, and 34 publications were finally included. Obesity was mainly measured by the body mass index, although other common types of evaluations were used (e.g., waist circumference, waist-to-hip ratio and plasma leptin levels). The selected neuroimaging analysis methods were voxel-based morphometry (VBM) and cortical thickness (CT), finding 21 and 13 publications, respectively. There were 30 cross-sectional and 2 prospective longitudinal studies, and 2 articles had both cross-sectional and longitudinal designs. Most studies showed a negative association between obesity and GMV. This would have important public health implications, as obesity prevention could avoid a potential risk of GMV reductions, cognitive impairment and dementia.

Frontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with different phenotypes, genetic backgrounds, and pathological states. Its clinicopathological diversity challenges the diagnostic process and the execution of clinical trials, calling for specific diagnostic biomarkers of pathologic FTD types. There is also a need for biomarkers that facilitate disease staging, quantification of severity, monitoring in clinics and observational studies, and for evaluation of target engagement and treatment response in clinical trials. This review discusses current FTD biofluidbased biomarker knowledge taking into account the differing applications. The limitations, knowledge gaps, and challenges for the development and implementation of such markers are also examined. Strategies to overcome these hurdles are proposed, including the technologies available, patient cohorts, and collaborative research initiatives. Access to robust and reliable biomarkers that define the exact underlying pathophysiological FTD process will meet the needs for specific diagnosis, disease quantitation, clinical monitoring, and treatment development.