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

Computerized cognitive training for older diabetic adults at risk of dementia: Study protocol for a randomized controlled trial

Introduction Older adults with type 2 diabetes are at high risk of cognitive decline and dementia and form an important target group for dementia risk reduction studies. Despite evidence that computerized cognitive training (CCT) may benefit cognitive performance in cognitively healthy older adults and those with mild cognitive impairment, whether CCT may benefit cognitive performance or improve disease self-management in older diabetic adults has not been studied to date. In addition, whether adaptive difficulty levels and tailoring of interventions to individuals' cognitive profile are superior to generic training remains to be established. Methods Ninety community-dwelling older (age ≥ 65) diabetic adults are recruited and randomized into a tailored and adaptive computerized cognitive training condition or to a generic, nontailored, or adaptive CCT condition. Both groups complete an 8-week training program using the commercially available CogniFit program. The intervention is augmented by a range of behavior-change techniques, and participants in each condition are further randomized into a global or cognition-specific phone-based self-efficacy (SE) condition, or a no-SE condition. The primary outcome is global cognitive performance immediately after the intervention. Secondary outcomes include diabetes self-management, meta-memory, mood, and SE. Discussion This pilot study is the first trial evaluating the potential benefits of home-based tailored and adaptive CCT in relation to cognitive and disease self-management in older diabetic adults. Methodological strengths of this trial include the double-blind design, the clear identification of the proposed active ingredients of the intervention, and the use of evidence-based behavior-change techniques. Results from this study will indicate whether CCT has the potential to lower the risk of diabetes-related cognitive decline. The outcomes of the trial will also advance our understanding of essential intervention parameters required to improve or maintain cognitive function and enhance disease self-management in this at-risk group.This study was conducted with the support of an MHS grant to Michal Schnaider-Beeri (grant no. 25860). The funding source played no role in the design and implementation of the trial, analysis and interpretation of the data, or preparation of the article. The CCT platform was donated by CogniFit. CogniFit or its employees played no role in the design and implementation of the trial, analysis and interpretation of the data, or preparation of the article. Rachel Bloom is supported by the Vice-Chancellor Award awarded to her by Bar Ilan University. Alex Bahar-Fuchs is supported by an Australian National Health and Medical Research Council fellowship (grant no. 1072688)

Computerized cognitive training for older adults at higher dementia risk due to diabetes: Findings from a randomized controlled trial

To evaluate the effects of adaptive and tailored computerized cognitive training on cognition and disease self-management in older adults with diabetesThis work was supported by Maccabi Health Services (MHS; grant no. 25860 to M.S.B.). The funding source played no role in the design and implementation of the trial, analysis and interpretation of the data, or preparation of the manuscript. The CCT platform was donated by CogniFit. CogniFit or its employees played no role in the design and implementation of the trial, analysis and interpretation of the data, or preparation of the manuscript. R.B. was supported by the Vice-Chancellor Award from Bar Ilan University, Israel. A.B-F. was supported by an Australian National Health and Medical Research Council fellowship (grant no. 1072688). M.S.B. was supported by the National Institute on Aging (grant no. R01-AG-034087). A.H. is an employee of MHS who provided funding for this study. The authors declare that they have no competing interests

Depressive Symptoms Are Associated with Cognitive Function in the Elderly with Type 2 Diabetes

Background: Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied. Objective: We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D. Methods: In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline study. For each cognitive domain (Episodic Memory, Executive Function, Attention/Working Mem- ory, Language/Semantic Categorization) and Overall Cognition, multiple linear regressions assessed its association with depression (score greater than 5 on the 15-item version of the Geriatric Depression Scale [GDS]), adjusting for age, sex, and education. Results: Depression (n = 66, 8.9%) was associated with worse performance on tasks of Executive Function (p = 0.004), Language/Semantic Categorization (p \u3c 0.001), and Overall Cognition (p \u3c 0.002), but not Episodic Memory (p = 0.643) or Attention/Working Memory (p = 0.488). Secondary analyses using GDS as a continuous variable did not sub- stantially change the results. Adjusting also for a history of antidepressant medication use slightly weakened the findings. Conclusion: Significant associations of depression with several cognitive domains and Overall Cognition even in cognitively normal elderly with T2D, suggest that depression may have a role in impaired cognitive function in T2D, which may be attenuated by antidepressants

Forebrain-specific transgene rescue of 11β-HSD1 associates with impaired spatial memory and reduced hippocampal BDNF mRNA levels in aged 11β-HSD1 deficient mice

Mice lacking the intracellular glucocorticoid‐regenerating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) are protected from age‐related spatial memory deficits. 11β‐HSD1 is expressed predominantly in the brain, liver and adipose tissue. Reduced glucocorticoid levels in the brain in the absence of 11β‐HSD1 may underlie the improved memory in aged 11β‐HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitisation and cardioprotective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β‐HSD1 deficient mice. In the present study, transgenic mice with forebrain‐specific overexpression of 11β‐HSD1 (Tg) were intercrossed with global 11β‐HSD1 knockout mice (HSD1KO) to examine the influence of forebrain and peripheral 11β‐HSD1 activity on spatial memory in aged mice. Transgene‐mediated delivery of 11β‐HSD1 to the hippocampus and cortex of aged HSD1KO mice reversed the improved spatial memory retention in the Y‐maze but not spatial learning in the watermaze. Brain‐derived neurotrophic factor (BDNF) mRNA levels in the hippocampus of aged HSD1KO mice were increased compared to aged wild‐type mice. Rescue of forebrain 11β‐HSD1 reduced BDNF mRNA in aged HSD1KO mice to levels comparable to aged wild‐type mice. These findings indicate that 11β‐HSD1 regenerated glucocorticoids in the forebrain and decreased levels of BDNF mRNA in the hippocampus play a role in spatial memory deficits in aged wild‐type mice, although 11β‐HSD1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice

Memory thieves? Representing dementia in Holocaust literature

This article examines the contemporary phenomenon of fiction and film about Holocaust survivors suffering from dementia. Earlier examples of this kind use dementia to explore the interior states of survivor guilt and the suppression of painful memories. By contrast, twenty-first-century representations convey the passing on of Holocaust memory to the next generation. These individuals, in the role of offspring or carers, act as the investigators and inheritors of a history that either has vanished from the survivor’s memory or appears in the present as if it were still taking place. Such works are expressive of cultural anxiety at the vanishing of the generation of eyewitnesses to the events of the Holocaust yet also act to defuse the unwelcome lessons such witnesses might impart

Reward components of feeding behavior are preserved during mouse aging

Eating behavior depends on associations between the sensory and energetic properties of foods. Healthful balance of these factors is a challenge for industrialized societies that have an abundance of food, food choices and food-related cues. Here, we were interested in whether appetitive conditioning changes as a function of age. Operant and pavlovian conditioning experiments (rewarding stimulus was a palatable food) in male mice (aged 3, 6, and 15 months) showed that implicit (non-declarative) memory remains intact during aging. Two other essential components of eating behavior, motivation and hedonic preference for rewarding foods, were also found not to be altered in aging mice. Specifically, hedonic responding by satiated mice to isocaloric foods of differing sensory properties (sucrose, milk) was similar in all age groups; importantly, however, this paradigm disclosed that older animals adjust their energy intake according to energetic need. Based on the assumption that the mechanisms that control feeding are conserved across species, it would appear that overeating and obesity in humans reflects a mismatch between ancient physiological mechanisms and today's cue-laden environment. The implication of the present results showing that aging does not impair the ability to learn stimulus-food associations is that the risk of overeating in response to food cues is maintained through to old age.This work was partly supported by European Commission's FP7 Initial Training Network NINA (Early Stage Researcher Fellowship to Mazen R. Harb) and Collaborative Project SwitchBox (to Osborne F. X. Almeida, Nuno Sousa and Joseph Zihl). The funding agencies had no influence over the design of experiments, interpretation of results or writing of the paper

Diabetes is associated with risk of postoperative cognitive dysfunction: a meta-analysis

BACKGROUND: Postoperative cognitive dysfunction (POCD) occurs frequently after surgery, particularly among older people. Diabetes, chronic hyperglycemia, and a history of hypoglycemia are related to cognitive impairment, but little is known about their roles in POCD. Here, we estimated their associations with risk of POCD on the basis of published epidemiological research. METHODS: The PubMed and Cochrane databases were searched for longitudinal studies of adults undergoing surgery with reporting of associations of diabetes status, glycemic levels, and/or a history of hypoglycemia with risk of POCD as relative risks or odds ratios. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: The search identified 246 publications of which 14 met inclusion criteria, reporting on a total of 2642 patients (mean age 64 y). Follow-up periods spanned 1 day to 5 years. Overall, patients with diabetes had a 1.26-fold higher risk of POCD compared with diabetes-free patients (95% CI, 1.12-1.42). A single study assessed glycemic control in patients with diabetes and identified a higher hemoglobin A1c (HbA1c) level as associated with higher POCD risk (relative risk per percent higher HbA1c, 2.0; 95% CI, 1.4-2.6). We did not find studies on glycemic levels in the nondiabetic range or on hypoglycemia as potential predictors of POCD. CONCLUSION: Patients with diabetes appear to have a higher risk of POCD compared with diabetes-free persons. Among patients with diabetes, POCD risk may further increase with poorer glycemic control as indexed by higher HbA1c. The roles of HbA1c levels among nondiabetic persons in POCD risk warrant further research