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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]

Purpose: To determine the pupil response of Best vitelliform macular dystrophy (BVMD) patients for focal blue and red light stimuli presented at 76 test points in a 16.2° visual field (VF) using a chromatic pupilloperimeter. Methods: An observational study was conducted in 16 participants: 7 BVMD patients with a heterozygous BEST1 mutation and 9 similar-aged controls. All participants were tested for best-corrected visual acuity, chromatic pupilloperimetry and Humphrey perimetry. Percentage of pupil contraction (PPC), maximal pupil contraction velocity (MCV) and latency of MCV (LMCV) were determined. Results: The mean PPC and MCV recorded in BVMD patients in response to red stimuli were lower by >2 standard errors (SEs) from the mean of controls in 47% and 43% of VF test points, respectively. The mean PPC and MCV recorded in the patients in response to blue stimuli were lower by >2 SEs from the mean of controls in 36% and 24% of VF test points, respectively. The patients' mean and median MCV recorded in response to red light correlated with their Humphrey mean deviation score (r=−0.714, P=0.071 and r=−0.821, P=0.023, respectively) and visual acuity (r=0.709, P=0.074 and r=0.655, P=0.111, respectively). A substantially shorter mean LMCV was recorded in BVMD patients compared to controls in 54% and 93% of VF test points in response to red and blue light, respectively. Receiver operating characteristic analysis for LMCV in response to red light identified a test point at the center of the VF with high diagnostic accuracy (area under the curve of 0.94). Conclusion: Chromatic pupilloperimetry may potentially be used for objective noninvasive assessment of rod and cone cell function in different locations of the retina in BVMD patients. [ABSTRACT FROM AUTHOR]

Introduction: We compared retinal layers' thickness between apolipoprotein E ( APOE ) Ɛ4 carriers and non-carriers in a cohort of cognitively normal middle-aged adults enriched for Alzheimer's disease (AD) risk., Methods: Participants (N = 245) underwent spectral domain optical coherence tomography. Multivariate analyses of covariance adjusting for age, sex, education, and best corrected vision acuity was used to compare retinal thickness between APOE groups., Results: Participants' mean age was 59.60 (standard deviation = 6.42) with 66.4% women and 32.2% APOE Ɛ4 carriers. Greater macular full thickness was observed in APOE Ɛ4 carriers compared to non-carriers ( P  = .017), reaching statistical significance for the inner and outer nasal ( P  = .009 and P  = .005, respectively), inner superior ( P  = .041), and inner and outer inferior ( P  = .013 and P  = .033, respectively) sectors. The differences between APOE groups were mainly driven by the ganglion cell layer ( P  < .05) and the inner plexiform layer ( P  < .05)., Discussion: A thicker macula is observed already in midlife asymptomatic APOE Ɛ4 carriers at high AD risk., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

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.)