The Association of Depressive Symptoms With Brain Volume Is Stronger Among Diabetic Elderly Carriers of the Haptoglobin 1-1 Genotype Compared to Non-carriers

Aim: Depression is highly prevalent in type 2 diabetes and is associated with lower adherence to medical treatments, worse glycemic control, and increased risk for diabetes-related complications. The mechanisms underlying depression in type 2 diabetes are unclear. The haptoglobin (Hp) genotype is associated with type 2 diabetes related complications including increased risk for cerebrovascular pathology and worse cognitive performance. Its relationship with depression is unknown. We investigated the role of Hp genotype on the association of depression with brain and white matter hyperintensities (WMH) volumes.Methods: Depressive symptoms (measured with the 15-item Geriatric Depression Scale), brain MRI, and Hp genotypes, were examined in elderly subjects with type 2 diabetes [29 (13.8%) Hp 1–1 carriers and 181 (86.2%) non-carriers]. The interaction of Hp genotype with number of depressive symptoms on regional brain measures was assessed using regression analyses.Results: The significant interactions were such that in Hp 1–1 carriers but not in non-carriers, number of depressive symptoms was associated with overall frontal cortex (p = 0.01) and WMH (p = 0.04) volumes but not with middle temporal gyrus volume (p = 0.43).Conclusions: These results suggest that subjects with type 2 diabetes carrying the Hp 1–1 genotype may have higher susceptibility to depression in the context of white matter damage and frontal lobe atrophy. The mechanisms underlying depression in diabetes may differ by Hp genotype

Linking Symptom Inventories using Semantic Textual Similarity

An extensive library of symptom inventories has been developed over time to measure clinical symptoms, but this variety has led to several long standing issues. Most notably, results drawn from different settings and studies are not comparable, which limits reproducibility. Here, we present an artificial intelligence (AI) approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories. We tested the ability of four pre-trained STS models to screen thousands of symptom description pairs for related content - a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding gains for both general and disease-specific clinical assessment

Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group

Abstract: The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant, and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with non-imaging biomarkers, genetics, as well as clinical and behavioral measures. Ultimately, we will offer investigators an unprecedented opportunity to test important hypotheses about recovery and morbidity in AMS-TBI by taking advantage of our robust methods for large-scale neuroimaging data analysis. In this consensus statement we outline the working group’s short-term, intermediate, and long-term goals

Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group

Abstract: The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant, and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with non-imaging biomarkers, genetics, as well as clinical and behavioral measures. Ultimately, we will offer investigators an unprecedented opportunity to test important hypotheses about recovery and morbidity in AMS-TBI by taking advantage of our robust methods for large-scale neuroimaging data analysis. In this consensus statement we outline the working group’s short-term, intermediate, and long-term goals

Effects of Ai-Chi Practice on Balance and Left Cerebellar Activation during High Working Memory Load Task in Older People: A Controlled Pilot Trial

Background: Normal aging is associated with balance and working memory decline. From a neurobiological standpoint, changes in cerebellar functional plasticity may mediate the decline in balance and working memory for older adults. Mounting evidence suggests that physical activity is beneficial for decreasing aging effects. Previous studies have focused on land-based physical activity and research concerning the aquatic environment is scarce. This study investigated the effectiveness of Ai-Chi on balance abilities and cerebral activation during a high working memory load task among community-dwelling older people. Methods: A total of 19 people aged 65–86 years were allocated to receive Ai-Chi practice (n = 6), structured on-land Ai-Chi practice (n = 7) or guided-imagery of Ai-Chi practice (n = 6) for a bi-weekly, 30-min exercise session for 12 weeks. Balance was measured by the Tinetti balance sub-test and working memory was measured by the N-back test during functional-MRI scan. Results: The Ai-Chi practice group presented a significant change in balance between pre and post intervention (balance t = −4.8, p < 0.01). In the whole-brain analysis, during high working memory load task, the Ai-Chi practice group presented a decrease in left cerebellar activation. Region of interest analyses yielded similar results by which pre-cerebellar activation was higher than post-intervention (t = 2.77, p < 0.05). Conclusions: Ai-Chi is an available, non-invasive intervention method that may serve as a tool to improve cerebellar activation that in turn might improve balance. In addition, our findings may provide new insights into the neuronal mechanisms that underlie both motor and cognitive abilities

A feasibility study of the combination of intranasal insulin with dulaglutide for cognition in older adults with metabolic syndrome at high dementia risk – Study rationale and design

INTRODUCTION: We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with dulaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits. METHODS: This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/dulaglutide injection, intranasal placebo/dulaglutide injection, INI/placebo injection, and intranasal placebo/placebo injection. Feasibility of combining INI with dulaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with dulaglutide (1.5 mg/week), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer's related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample. DISCUSSION: This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial of the cognitive benefits of the combination of INI with dulaglutide in individuals enriched for CVD and at high dementia risk

The <i>CADM2</i> gene is associated with processing speed performance – evidence among elderly with type 2 diabetes

<p><b>Objectives:</b> 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 (<i>CADM2</i>) 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.</p> <p><b>Methods:</b> 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.</p> <p><b>Results:</b> Controlling for sex, age at cognitive assessment, years of education and ancestry, we found a significant association of rs17518584 with DSST performance (<i>P</i> = 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 (<i>P</i> = 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.</p> <p><b>Conclusions:</b> Taken together, irrespective of T2D-related characteristics and cardiovascular factors, our findings provide independent support for the association of <i>CADM2</i> SNP rs17518584 with processing speed (and demonstrate association with additional cognitive phenotypes), among cognitively normal elderly individuals with T2D.</p

Table_1_Neural correlates of subjective cognitive decline in adults at high risk for Alzheimer’s disease.DOCX

IntroductionRecently, interest has emerged in subjective cognitive decline (SCD) as a potential precursor to Alzheimer’s disease (AD) dementia. Whether individuals with SCD harbor brain alterations in midlife, when AD-related pathology begins, is yet to be elucidated. Furthermore, the role of apolipoprotein ε4 (APOE ε4) allele, a robust AD risk factor, in the relationship between SCD and brain alterations is unknown. We examined whether APOE genotype modulates the association of SCD with brain measures in individuals at high AD risk.MethodsMiddle-aged adults with parental history of AD dementia underwent magnetic resonance imaging (MRI) and the Memory Functioning Questionnaire. Regression analysis tested the extent to which SCD was associated with activation during an functional MRI (fMRI) working-memory task, and white-matter microstructure. APOE ε4 genotype was tested as a moderator.ResultsAmong APOE ε4 carriers, but not among non-carriers, SCD was associated with higher activation in the anterior cingulate (p = 0.003), inferior, middle, and superior frontal cortices (p = 0.041, p = 0.048, p = 0.037, respectively); and with lower fractional anisotropy in the uncinate fasciculus (p = 0.002), adjusting for age, sex, and education.ConclusionIn middle aged, cognitively normal individuals at high AD risk, higher SCD was associated with greater brain alterations possibly reflecting incipient AD pathology. When accompanied by a family history of AD and an APOE ε4 allele, SCD may have important clinical value, allowing a window for early intervention and for participants’ stratification in AD prevention clinical trials.</p