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Background: Numerous studies have identified an increased risk for Alzheimer's dementia (AD) in Type II Diabetes (T2D). However, the T2D biological characteristics contributing to this risk are still unknown. Adiposity assessed by body mass index (BMI) is one of the main causes of T2D and has been consistently linked to higher dementia risk, faster cognitive decline, and related neural injury. However, the contribution of fat specifically cannot be derived from BMI, which encompasses different adipose tissues, bone, and muscle mass. In this study we examined whether regional abdominal adiposity contributes to AD‐related regional brain volume and mechanism underlying it, in older adults with T2D participating in the Israel Diabetes and Cognitive Decline (IDCD) study. Method: Regional abdominal adiposity was measured so far in 60 participants, including hepatic and pancreatic adiposity and abdominal adipose tissue (AAT), composed of subcutaneous and visceral adipose tissues (SAT and VAT). Brain volumes were assessed for regions associated with cognitive decline (hippocampus, cingulate gyrus, amygdala, and ventromedial prefrontal cortex (vmPFC)). Linear regressions examined associations of regional abdominal adiposity with regional brain volumes adjusting for sociodemographics, BMI and intracranial volume. We also tested if triglycerides, the main components of fat and associated with dementia risk, mediated these associations. Result: Greater VAT:AAT ratio was associated with smaller volumes of the vmPFC (r = ‐0.38; p = 0.026) and hippocampal (r = ‐0.44; p = 0.005) volumes but not with amygdala and cingulate gyrus volumes. The SAT:AAT ratio was associated with greater volumes of the vmPFC (r = 0.40; p = 0.026) and hippocampus (r = 0.48; p = 0.004) but not with amygdala and cingulate. No associations were found between hepatic and pancreatic adiposity with brain volumes. Higher VAT:AAT ratio was associated with higher triglyceride levels (r = 0.38; p = 0.036) which in turn were associated with lower hippocampal volume (r = ‐0.45, p = 0.05). Triglycerides partially mediated the association between VAT:AAT ratio and hippocampal volume (r = ‐0.36; p = 0.03). Triglycerides did not mediate any other associations. Conclusion: In older adults with T2D, a higher proportion of visceral fat may have a detrimental impact on brain regions relevant to cognitive functioning. Higher proportions of subcutaneous fat may have a protective role. Triglycerides, implicated in insulin resistance and chronic systemic inflammation may mediate the VAT‐hippocampus link. [ABSTRACT FROM AUTHOR]

Objectives: Recent large-scale meta-analysis of genome-wide association studies (GWAS) from multiple cohorts, demonstrated the association of the single nucleotide polymorphism (SNP) rs17518584, with processing speed (measured by the Digit Symbol Substitution Test (DSST) or the Letter Digit Substitution Test (LDST)), at GWAS significance level. This SNP is located within the cell adhesion molecule 2 (CADM2) gene. We aimed to validate this finding in our sample of 944 cognitively normal Jewish elderly individuals with type 2 diabetes (T2D), a population which is at risk for cognitive decline and dementia. Methods: Using linear regression, we studied the association of rs17518584 with DSST performance, adjusting for demographic, T2D-related characteristics and cardiovascular factors. In secondary analyses, associations with performance in four cognitive domains (episodic memory, language/semantic categorisation, attention/working memory and executive function) and overall cognition were examined. Results: Controlling for sex, age at cognitive assessment, years of education and ancestry, we found a significant association of rs17518584 with DSST performance (P = 0.013), consistent with the originally reported effect direction. Results remained significant even when the additional covariates (T2D-related and cardiovascular factors) were included in the analysis (P = 0.034). Moreover, this SNP was significantly associated with performance in the cognitive domains of language/semantic categorisation and executive function, as well as overall cognition. Conclusions: Taken together, irrespective of T2D-related characteristics and cardiovascular factors, our findings provide independent support for the association of CADM2 SNP rs17518584 with processing speed (and demonstrate association with additional cognitive phenotypes), among cognitively normal elderly individuals with T2D. [ABSTRACT FROM AUTHOR]

Introduction: We examined relationships of body mass index (BMI) with cognition in middle-aged adults at Alzheimer's disease (AD) risk due to parental family history., Methods: Participants are offspring of AD patients from the Israel Registry of Alzheimer's Prevention (N = 271). Linear regressions assessed associations of BMI and cognition, and whether associations differed by maternal/paternal history. Analyses of covariance examined associations of long-term trajectories of BMI with cognition., Results: Higher BMI was associated with worse language ( P  = .045). Interactions of BMI with parental history were significant for episodic memory ( P  = .023), language (p = .027), working memory ( P  = .006), global cognition ( P  = .008); associations were stronger among participants with maternal history. Interactions of BMI trajectories with parental history were significant for episodic memory ( P  = .017), language ( P  = .013), working memory ( P  = .001), global cognition ( P  = .005), with stronger associations for maternal history., Discussion: Higher BMI and overweight/obese trajectories were associated with poorer cognition in adults with maternal history of AD, but not those with paternal history., Competing Interests: Rebecca K. West reports that in addition to her work at the Icahn School of Medicine at Mount Sinai, she is paid as an adjunct assistant professor and a researcher at the City University of New York. Ramit Ravona‐Springer received funding from Tel Aviv University internal grants—the Brecher foundation and the Ofer Mordechai Foundation, the ARC (Accelerate, Redesign, Collaborate) Innovation Center at the Sheba Medical Center, the ADDF (Alzheimer's Drug Discovery Foundation). Inbal Sharvit Ginon received travel support for attending AAIC 2018 and AAIC 2019, as PhD student at the Joseph Sagol Neuroscience Center at Sheba Medical Center, Israel. Ithamar Ganmore reports no disclosures. Sigalit Manzali reports no disclosures. Sapir Golan reports no disclosures. Ethel Boccara reports no disclosures.Anthony Heymann received consulting fees from pharmaceutical companies Boehringer Ingelheim Israel, Rafa Israel, and Kamada, and payment for expert testimony in medical negligence cases in Israel courts. Michal Schnaider Beeri reports no disclosures., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)