Poor self-rated health is associated with faster cognitive decline and greater small vessel disease in older adults with type 2 diabetes.

OBJECTIVE: Self-rated health (SRH) is a predictor for poor health outcomes and cognition. Older adults with type 2 diabetes mellitus (T2D) have multi-morbidity and greater cognitive impairment. In the present study we investigated the association of SRH with cognitive decline and brain pathology in older adults with T2D. METHODS: Participants (n = 1122) were from the Israel Diabetes and Cognitive Decline study, and SRH was categorised as low (n = 202), moderate (n = 400) or high (n = 520). Cognition was measured by four cognitive domains: episodic memory, executive functions, language, and attention/working memory. Global cognition was the average of the cognitive domains. Statistical models adjusted for sociodemographic, cardiovascular, and clinical variables. In a randomly selected subsample (n = 230) that had magnetic resonance imaging, we examined relationships between baseline SRH and brain characteristics (white matter hyperintensities [WMHs], hippocampal, and total grey matter [GM] volumes). RESULTS: Low SRH was associated with a decline in executive functions, which accelerated over time when compared to high SRH (est = -0.0036; p = <0.001). Compared to high SRH, low SRH was associated with a faster decline in global cognition (est = -0.0024; p = 0.009). Low SRH at baseline was associated with higher volumes of WMHs (est = 9.8420; p < 0.0008). SRH was not associated with other cognitive domains, or with hippocampal and total GM. CONCLUSIONS: Low SRH is associated with cognitive decline in T2D older adults and may serve as a risk assessment. WMHs may represent an underlying mechanism.

Behavioral and Brain Correlates of Emotional Distress in Older Adults During COVID-19 Quarantine.

COVID-19 led to unprecedented lockdowns and changes in older adults' lives, especially those with type 2 diabetes who have high risk of complications and mortality. We investigated the associations of cognitive and motor function and gray matter volumes (GMVs) with COVID-19 lockdown-related emotional distress of type 2 diabetes older adults, participating in the Israel Diabetes and Cognitive Decline Study. We administered a questionnaire to obtain information about anxiety, depression, general well-being, and optimism during a mandated lockdown. Lower grip strength before lockdown was associated with increased sadness, anxiety, and less optimism. Slower gait speed was associated with greater sadness. Lower GMV was related to greater anxiety during the lockdown when compared with anxiety levels before the COVID-19 outbreak. Yet, global cognition was not associated with any emotional distress measure. These results support the role of good motor function on emotional well-being during acute stress and GMV as a potential underlying mechanism.

Neuroticism is associated with increase in depression symptoms over time in older adults with type 2 diabetes.

OBJECTIVES: The likelihood of depression symptoms in those with type 2 diabetes (T2D) is high. Psychological risk factors enhancing comorbidity of depression symptoms in T2D are yet to be determined. The present study examines the cross-sectional and longitudinal relationship between personality traits and distinct depression dimensions in older adults with T2D. METHODS: Participants were older adults (age ≥65yeas) with T2D from the Israel Diabetes and Cognitive Decline (IDCD) study (N = 356), with complete data on depression [Geriatric Depression Scale (GDS) - 15 item version] and its dimensions- namely, dysphoric mood, apathy, hopelessness, memory complains and anxiety, and on personality [Big Five Inventory (BFI)]. Logistic and mixed linear regression models examined cross-sectional and longitudinal associations while adjusting for socio-demographics, cognition, cardiovascular and diabetes-related factors. RESULTS: Cross-sectionally, high neuroticism was associated with high scores in total GDS and in all depression-dimensions, except memory complaints. Higher extroversion was associated with lower total GDS and with lower scores on all depression dimensions, except anxiety. High levels of neuroticism were associated with increase in total number of depression symptoms over time. CONCLUSIONS: In older adults with T2D, neuroticism and extroversion are associated with most depression dimensions suggesting that these traits relate to a global depression symptomatology rather than to any specific dimension or phenomenology. High neuroticism was associated with increase in depression symptoms over time, highlighting its role in the development of depression symptoms in older adults with T2D.

[SLEEP MONITORING FOR PREDICTION OF MAJOR DEPRESSION RECURRENCE IN PATIENTS AT HIGH RISK - A PROSPECTIVE STUDY].

INTRODUCTION: Objective: To examine the feasibility of sleep monitoring using an innovative wearable technology, as a predictive tool for MDE (major depressive episode) recurrence in high risk patients.

Increase in Number of Depression Symptoms Over Time is Related to Worse Cognitive Outcomes in Older Adults With Type 2 Diabetes.

OBJECTIVE: Older adults with type 2 diabetes (T2D) are at increased risk for depression, cognitive decline, and dementia compared to those without T2D. Little is known about the association of simultaneous changes in depression symptoms and cognitive decline over time. METHODS: Subjects (n=1021; mean age 71.6 [SD=4.6]; 41.2% female) were initially cognitively normal participants of the Israel Diabetes and Cognitive Decline study who underwent evaluations of depression and cognition approximately every 18 months. Cognitive tests were summarized into four cognitive domains: episodic memory, attention/working memory, executive functions, and semantic categorization. The average of the z-scores of the four domains defined global cognition. Depression symptoms were assessed using the Geriatric Depression Scale, 15-item version. We fit a random coefficients model of changes in depression and in cognitive functions, adjusting for baseline sociodemographic and cardiovascular variables. RESULTS: Higher number of depression symptoms at baseline was significantly associated with lower baseline cognitive scores in global cognition (estimate = -0.1175, SE = 0.021, DF = 1,014, t = -5.59; p < 0.001), executive functions (estimate = -0.186, SE = 0.036, DF = 1,013, t = -5.15; p = <0.001), semantic categorization (estimate = -0.155, SE = 0.029, DF = 1,008, t = -5.3; p < 0.001), and episodic memory (estimate = -0.08165, SE = 0.027, DF = 1,035, t = -2.92; p = 0.0036), but not with rate of decline in any cognitive domain. During follow-up, a larger increase in number of depression symptoms, was associated with worse cognitive outcomes in global cognition (estimate = -0.1053, SE = 0.027, DF = 1,612, t = -3.77; p = 0.0002), semantic categorization (estimate = -0.123, SE = 0.036, DF = 1,583, t = -3.36; p = 0.0008), and in episodic memory (estimate = -0.165, SE = 0.055, DF = 1,622, t = -3.02; p = 0.003), but the size of this effect was constant over time. CONCLUSION: In elderly with T2D, increase in depression symptoms over time is associated with parallel cognitive decline, indicating that the natural course of the two conditions progresses concurrently and suggesting common underlying mechanisms".

Executive functioning of older adults with bipolar disorder.

OBJECTIVES: Despite their impact on daily functioning, we have limited understanding of the executive functioning of older adults with bipolar disorder (OABD). Even less is known about the possible differences in the executive functioning of OABD and older adults with unipolar depression (OADEP). METHODS: After excluding acutely ill patients, the executive functioning of OABD was compared to that of OADEP and healthy controls (n = 22, n = 20, n = 22; respectively). Cognitive insight, a sub-domain of executive functioning, was operationalized as the discrepancy between the participants' self-reported cognitive functioning and appraisals that were made by their care partners. To complement the cognitive profiling, the groups were compared in information processing speed, verbal memory, and visual-spatial memory. RESULTS: OABD were impaired in several cognitive domains compared to healthy controls, most prominently in executive functioning and memory. OABD had poorer executive functioning and visual-spatial memory than OADEP. The findings also tentatively point toward intact cognitive insight among OABD, while OADEP seem to have a heightened level of awareness of their cognitive impairment. CONCLUSIONS: OABD have a unique profile of cognitive impairment compared to OADEP. It is characterized by a more severe cognitive impairment, accompanied by relatively intact cognitive insight. The findings may help clarify the cognitive profile of OABD and assist in the development of cognitive rehabilitation programs tailored to their needs. They should, however, be considered preliminary and await further research.

Trajectories of depression symptoms over time differ by APOE4 genotype in older adults with type 2 diabetes.

OBJECTIVES: The APOE-ε4 genotype has been associated with old-age depression, but this relationship has been rarely investigated in type 2 diabetes (T2D) older adults, who are at significantly increased risk for depression, a major contributor to T2D complications. We examined whether trajectories of depression symptoms over time differ by APOE-ε4 genotype in older adults with T2D. METHODS: Participants (n = 754 [13.1% APOE-ε4 carrier]s) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of depression approximately every 18 months using the 15-item version of the Geriatric Depression Scale (GDS) and the depression subscale of the Neuropsychiatric Inventory (NPI). APOE was defined as a dichotomy of ε4 carriers and non-carriers. We used Hierarchical Linear Mixed Models (HLMM) that modeled the effects of APOE status on repeated GDS and NPI-depression scores in an unadjusted model (Model 1), adjusting for demographic factors (Model 2) and additionally adjusting for cardiovascular factors and global cognition (Model 3). RESULTS: Participants' mean age was 71.37 (SD = 4.5); 38.2% female. In comparison to non-carriers, APOE-ε4 carriers had lower mean GDS scores (ß = -0.46, p = 0.018) and lower NPI-depression scores (ß = -0.170, p = 0.038) throughout all study follow period. The groups did not differ in the slope of change over time in GDS (ß = -0.005, p = 0.252) or NPI-depression (ß = -0.001, p = 0.994) scores. Additional adjustment for cardiovascular factors and global cognition did not alter these results. CONCLUSIONS: In older adults with T2D, APOE-ε4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression.

Physical fitness mediates the association between age and cognition in healthy adults.

BACKGROUND: Physical fitness is an important contributor to healthy aging that improves cognition. Older adults who engage in cardiorespiratory fitness activities show less cognitive decline. AIMS: To examine whether physical fitness acts as a potential protective mechanism shielding against the negative associations between age and cognition. Specifically, we examined whether physical fitness mediates the relationship between age and processing speed. METHODS: 114 (M = 63.80, SD = 10.63) senior executives completed a computerized cognitive battery composed of four processing speed tasks. Level of physical fitness was assessed on a treadmill stress test and reported in metabolic equivalents (METs). RESULTS: Older age was associated with slower processing speed (r = 0.25, p = 0.007), whereas greater physical fitness was associated with faster processing speed (r = -0.30, p = 0.001). Path analysis indicated that the association between age and processing speed was fully mediated by the level of physical fitness (Indirect effect: ß = 0.10, p = 0.008; Direct effect: ß = 0.16, p = 0.20). CONCLUSIONS AND DISCUSSION: The findings indicate that physical fitness is a strong mediator of the relationship between age and processing speed and imply that physical fitness makes a major contribution to cognitive reserve during the aging process. The results may suggest that the decrease in physical fitness during aging may partially account for slower cognitive processing.

Higher BMI is associated with smaller regional brain volume in older adults with type 2 diabetes.

AIMS/HYPOTHESIS: There are established relationships between adiposity (obesity) and higher dementia risk, faster cognitive decline and associated neural injury. Type 2 diabetes is strongly linked to greater adiposity and has been consistently associated with neural injury and poor cognitive outcomes. However, although obesity is a major cause of type 2 diabetes, there is limited evidence on the association of adiposity with brain atrophy among individuals with type 2 diabetes. METHODS: We examined the association of BMI (a measure of adiposity), and of long-term trajectories of BMI (three empirically identified groups of trajectories-'normal', 'overweight' and 'obese'-using SAS macro PROC TRAJ), with regional brain volume, in a sample of older individuals (aged 64-84) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline Study (n = 198). RESULTS: Using linear regression, we found that greater BMI was associated with smaller volumes of the inferior frontal gyrus (IFG) (r = -0.25, p = 0.001) and the middle temporal gyrus (r = -0.19; p = 0.010) after adjusting for sociodemographic covariates and total intracranial volume. In addition, there were significant differences between BMI trajectory groups in IFG volume (F = 4.34, p = 0.014), such that a long-term trajectory of obesity was associated with a smaller volume. Additional adjustment for cardiovascular and diabetes-related potential confounders did not substantively alter the results. There were no associations of adiposity with superior frontal gyrus, middle frontal gyrus or total grey matter volumes. CONCLUSIONS/INTERPRETATION: In older adults with type 2 diabetes, long-term adiposity may have a detrimental impact on volume of brain regions relevant to cognitive functioning. Further studies to identify the underlying mechanisms are warranted. Graphical abstract.

Long-term trajectories of BMI predict carotid stiffness and plaque volume in type 2 diabetes older adults: a cohort study.

BACKGROUND: High body mass index (BMI) is a risk factor for type 2 diabetes and cardiovascular disease. However, its relationships with indices of carotid stiffness and plaque volume are unclear. We investigated associations of long-term measurements of BMI with indices of carotid stiffness and atherosclerosis among non-demented diabetes patients from the Israel Diabetes and Cognitive Decline (IDCD) study. METHODS: Carotid ultrasound indices [carotid intima media thickness (cIMT), distensibility, elastography and plaque volume] were assessed in N = 471 participants. Mean BMI across all MHS diabetes registry measurements and trajectories of BMI were calculated. BMI was categorized into three trajectory groups representing: a relatively stable normal weight (n = 185, 44%), overweight trajectory (n = 188, 44.8%) and a trajectory of obesity (n = 47, 11.2%). Linear and logistic regressions estimated associations of carotid indices with mean BMI and BMI trajectories. RESULTS: Compared to the normal weight trajectory, an obesity trajectory was associated with carotid distensibility (ß = - 3.078, p = 0.037), cIMT (ß = 0.095, p = 0.004), and carotid elastography (ß = 0.181, p = 0.004) but not with plaque volume (ß = 0.066, p = 0.858). Compared with the normal weight trajectory, an obesity trajectory was associated with increased odds for impaired carotid distensibility (OR = 2.790, p = 0.033), impaired cIMT (OR = 5.277, p = 0.001) and large carotid plaque volume (OR = 8.456, p = 0.013) but not with carotid elastography (OR = 1.956, p = 0.140). Mean BMI was linearly associated with Distensibility (ß = - 0.275, p = 0.005) and cIMT (ß = 0.005, p = 0.026). CONCLUSIONS: Long-term measurements of adiposity are associated with indices of carotid stiffness and plaque volume among older type 2 diabetes adults.

Deterioration in Motor Function Over Time in Older Adults With Type 2 Diabetes is Associated with Accelerated Cognitive Decline.

OBJECTIVE: Type 2 diabetes (T2D) is associated with motor impairments and a higher dementia risk. The relationships of motor decline with cognitive decline in T2D older adults has rarely been studied. Using data from the Israel Diabetes and Cognitive Decline study (N = 892), we examined associations of decline in motor function with cognitive decline over a 54-month period. METHODS: Motor function measures were strength (handgrip) and gait speed (time to walk 3 m). Participants completed a neuropsychologic battery of 13 tests transformed into z-scores, summarized into 4 cognitive domains: episodic memory, attention/working memory, executive functions, and language/semantic categorization. The average of the 4 domains' z-scores defined global cognition. Motor and cognitive functions were assessed in 18-months intervals. A random coefficients model delineated longitudinal relationships of cognitive decline with baseline and change from baseline in motor function, adjusting for sociodemographic, cardiovascular, and T2D-related covariates. RESULTS: Slower baseline gait speed levels were significantly associated with more rapid decline in global cognition (P = .004), language/semantic categorization (P = .006) and episodic memory (P = .029). Greater decline over time in gait speed was associated with an accelerated rate of decline in global cognition (P = .050), attention/working memory (P = .047) and language/semantic categorization (P<.001). Baseline strength levels were not associated with cognitive decline but the rate of declining strength was associated with an accelerated decline in executive functions (P = .025) and language/semantic categorization (P = .006). CONCLUSION: In T2D older adults, the rate of decline in motor function, beyond baseline levels, was associated with accelerated cognitive decline, suggesting that cognitive and motor decline share common neuropathologic mechanisms in T2D.

C-reactive protein in midlife is associated with depressive symptoms two decades later among men with coronary heart disease.

Aim: We investigated the relationship between midlife C-reactive protein (CRP) levels in men with coronary heart disease (CHD) and depressive symptoms at old age. CRP levels were measured in a subset of patients with CHD, who previously participated in a secondary prevention trial.Methods: Depressive symptoms were evaluated in survivors of the original cohort 15.0 ± 3 and 19.9 ± 1 years later (T1, n = 463 and T2, n = 314 respectively) using the Geriatric Depression Scale (GDS), 15-item version. Logistic regression was used to estimate ORs and 95%CIs for presence of potentially clinically significant depressive symptoms (GDS ≥5) at T1 and T2.Results: Adjusting for demographic and health-related variables, the OR (95%CI) for GDS ≥5 was 1.23 (0.65-2.33); p = .53 at T1 and 2.36 (1.16-4.83); p = .018 at T2 in the top CRP tertile compared to the others. Similarly, consistently high CRP levels in the top tertile at baseline and 2 years later, were associated with OR of 2.85 (95%CI 1.29-6.30); p = .01 for GDS ≥5 at T2.Conclusions: Presence and persistence of low-grade inflammation in men with CHD during midlife are associated with increased risk of depressive symptoms twenty years later. Among middle aged men with CHD, low-grade inflammation may provide an important added value for prediction of depression in old age.

Depression is more strongly associated with cognition in elderly women than men with type 2 diabetes.

Depression and cognitive impairment are highly prevalent in type 2 diabetes (T2D), yet little is known about how their relationship varies by sex. We examined this question in a large T2D sample (N = 897) of non-demented elderly (≥ 65) participating in the Israel Diabetes and Cognitive Decline (IDCD) Study. Cognition was evaluated by a comprehensive neuropsychological battery and depressive symptoms were assessed by the Geriatric Depression Scale (GDS). The results showed that in all but the executive function domain, the association of depressive symptoms with poorer cognitive function was stronger in women than men, with a significant interaction for language/semantic categorization and missed significance for episodic memory. When defining clinical depression as GDS of ≥6, women with depression had significantly poorer language/semantic categorization, episodic memory, and overall cognitive function. Inclusion of antidepressants in the model did not alter substantively the associations. Our results suggest that depressed T2D women may have poorer cognitive performance, highlighting the significance of sex-specific personalized management of depression in elderly diabetics.

Personality traits and cognitive function in old-adults with type-2 diabetes.

Objectives: Personality may constitute an important domain of influence on cognitive function in old-adults. We assessed the relationship of personality traits and cognitive performance in individuals with Type-2 Diabetes (T2D), and explored possible mediators. Method: The sample includes 377 dementia-free subjects with T2D participating in the Israel Diabetes and Cognitive Decline study who underwent assessment of cognition and personality (mean age 72 ± 4y; 42% females). We assessed the relationships of personality traits with episodic memory, semantic categorization, attention/working memory, executive function and overall cognition using linear regression models adjusting for age, education, sex, BMI, T2D duration, Hemoglobin A1C (HbA1C), hypertension, c-reactive protein, total- to HDL-cholesterol ratio and ApoEɛ4 genotype. A post-hoc mediation analysis was conducted with HbA1C, proportion of days covered (PDC) by T2D prescription claims and depressive symptoms. Results: After adjustment for multiple covariates, high neuroticism levels were associated with poorer performance overall (ß= -0.16 ± 0.05; p = 0.001) and with poorer episodic memory, attention/working memory, and semantic categorization (ß= -0.14 ± 0.05; p = 0.007, ß= -0.12 ± 0.05; p = 0.017 and ß= -0.12 ± 0.05; p = 0.018, respectively). High scores on openness to experience were associated with better global cognition (ß = 0.11 ± 0.05; p = 0.026), executive functions (ß = 0.13 ± 0.05; p = 0.013) and semantic categorization (ß = 0.17 ± 0.05; p = 0.001, respectively). Depressive symptoms mediated the association of neuroticism with executive function, and the association of openness with executive function and overall cognition. Conclusion: Personality may play an important role in cognitive health among elderly subjects with T2D. Future studies should address the mechanisms underlying these relationships and specifically the potential role of depressive symptoms which may be in the causal pathway between personality traits and cognitive outcomes.

Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes.

OBJECTIVE: The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. METHODS: This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. RESULTS: Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. CONCLUSIONS: Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics.

Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women.

INTRODUCTION: Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. METHODS: We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). RESULTS: In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance (P < .0001), executive functioning (P = .026), and overall cognition (P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes-related, APOE ε4, and inflammatory potential confounders. Attention/working memory (P = .532) and episodic memory (P = .144) were not associated with waist circumference. These correlations were not found in men. DISCUSSION: These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia.

Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes.

AIMS/HYPOTHESIS: The purpose of this study was to investigate whether the association of glycaemic control with cognitive function is modulated by the haptoglobin 1-1 (Hp 1-1) genotype in cognitively normal elderly individuals with type 2 diabetes. METHODS: In this cross-sectional study, we examined 793 participants who were genotyped for Hp (80 Hp 1-1 carriers and 713 Hp 1-1 non-carriers) enrolled in the Israel Diabetes and Cognitive Decline (IDCD) study. Glycaemic control was operationally defined by HbA1c level. The outcome measures were performance in four cognitive domains (episodic memory, attention/working memory, language/semantic categorisation, executive function) and overall cognition, a composite of the domains. Effect sizes were obtained from hierarchical linear regression analyses for each outcome measure, controlling for demographics, type 2 diabetes-related characteristics, cardiovascular risk factors, and their interactions with Hp genotype. RESULTS: Interaction analyses showed significantly stronger associations of HbA1c with poorer cognitive function among Hp 1-1 carriers than non-carriers; attention/working memory (p < 0.001) and overall cognition (p = 0.003). For these two cognitive domains, associations were significant for Hp 1-1 carriers despite the small sample size (p < 0.00001 and p = 0.001, respectively), but not for non-carriers. CONCLUSIONS/INTERPRETATION: Our findings suggest that patients with type 2 diabetes and poor glycaemic control carrying the Hp 1-1 genotype may be at increased risk of cognitive impairment, particularly in the attention/working memory domain. The association of glycaemic control with this domain may indicate cerebrovascular mechanisms.

Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes.

OBJECTIVE: Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes. METHODS: A retrospective cohort study of 777 randomly selected participants from ~11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (±9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects' performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization. RESULTS: Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r = -0.166, p = 0.011), executive functions (r = -0.136, p = 0.038), and overall cognition (r = -0.157, p = 0.016). CONCLUSIONS: Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes.

Considerations in psychotropic treatments in dementia--can polypharmacy be avoided?

Physicians treating demented individuals are confronted with complex clinical presentations. This complexity results from the multi-factorial nature of clinical phenomena, the aetiologies of these phenomena, which differ from similar symptoms in younger populations, limited physiological reserves and the multiple co-morbidities and medications. This intricacy is well exemplified within the clinical presentation and management of psychological and behavioural symptoms of dementia. The latter are associated with a poor quality of life, increased burden for both patient and caregivers. A further challenge and source for frustration is the fact that many of the medications used to treat cognitive and behavioural symptoms of dementia are only marginally effective or not effective at all, on the one hand, and associated with increased risk for morbidity and mortality on the other hand. In the present review, we discuss these factors in the context of polypharmacy and suggest further clinical and research strategies that may enable more accurate and less harmful therapeutic strategies.