Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes.

ObjectiveIndividuals with type 1 diabetes have experienced an increase in life expectancy, yet it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes.Research design and methodsWe followed 3,433 members of a health care system with type 1 diabetes, aged ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A1c (HbA1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA1c measurement.ResultsOver a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA1c measurements at 8-8.9% (64-74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with <50% of measurements exposed (HbA1c 8-8.9% adjusted hazard ratio [aHR] 1.65 [95% CI 1.06, 2.57] and HbA1c ≥9% aHR 1.79 [95% CI 1.11, 2.90]). By contrast, patients with ≥50% of HbA1c measurements at 6-6.9% (42-52 mmol/mol) and 7-7.9% (53-63 mmol/mol) had a 45% lower risk of dementia (HbA1c 6-6.9% aHR 0.55 [95% CI 0.34, 0.88] and HbA1c 7-7.9% aHR 0.55 [95% CI 0.37, 0.82]).ConclusionsAmong older patients with type 1 diabetes, those with majority exposure to HbA1c 8-8.9% and ≥9% had increased dementia risk, while those with majority exposure to HbA1c 6-6.9% and 7-7.9% had reduced risk. Currently recommended glycemic targets for older patients with type 1 diabetes are consistent with healthy brain aging

Cognitive dysfunction in diabetes: how to implement emerging guidelines

Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognised as an important comorbidity and complication of diabetes that affects an individual's well-being and diabetes management, and is associated with diabetes treatment-related complications. Recent guidelines therefore recommend screening for cognitive impairment in older individuals with diabetes. In addition, these guidelines suggest that glucose-lowering treatment should be tailored in those diagnosed with cognitive impairment, to reduce the risk of hypoglycaemia and improve treatment adherence. This review gives an overview of cognitive dysfunction in people with diabetes, briefly describing the clinical features of different stages of cognitive dysfunction and their epidemiology. In particular, it addresses essential additional steps that need to be taken to fully implement the emerging guidelines on screening and management of cognitive dysfunction in diabetes into daily practice

Sex, Diabetes Status and Cognition: Findings from the Study of Longevity in Diabetes

INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk. RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders. RESULTS: We included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI -0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes. CONCLUSIONS: Women in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia

Development of a machine learning algorithm to predict the residual cognitive reserve index

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience

Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases

Association of primary lifetime occupational cognitive complexity and cognitive decline in a diverse cohort: Results from the KHANDLE study

IntroductionHigher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations.MethodsIn a diverse cohort (n = 1536), linear mixed-effects models estimated associations between main lifetime occupational complexity and domain-specific cognitive decline (z-standardized). Occupational complexity with data, people, and things were classified using the Dictionary of Occupational Titles.ResultsFor occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (β = 0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (β = 0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (β = 0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (β = 0.29; 95% CI 0.18-0.40), verbal episodic memory (β = 0.12; 95% CI 0.00-0.24), and semantic memory (β = 0.23; 95% CI 0.12-0.34).DiscussionIn a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts.HighlightFew studies have examined associations of occupational complexity with cognition in diverse populations. Racial and ethnic minorities are disproportionately exposed to lower occupational complexity. Occupational complexity with data and people are associated with better cognition

Gender differences in the association between education and late‐life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest–old

IntroductionFew studies have examined the relationship between education and cognition among the oldest-old.MethodsCognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (< high school, high school, some college, and ≥ college) and cognition (verbal episodic memory, semantic memory, and executive function) were examined at baseline and longitudinally using linear mixed models.ResultsHigher education levels were associated with better cognitive performance at baseline for both men and women. College completion was more strongly associated with better baseline executive function among women. Education-cognition associations for baseline verbal episodic memory and baseline semantic memory did not differ by gender. Education was not associated with a decline in any domain-specific cognitive scores, regardless of gender.DiscussionEducation is associated with cognitive function among the oldest-old and varies by gender and cognitive domain at baseline but not over time.HighlightsIn the oldest-old, higher education was associated with better cognitive function. College completion was more strongly associated with executive function in women. Education was not associated with cognitive decline after age 90 regardless of gender. Improving education could decrease gaps in cognitive level among older individuals

HbA1c variability associated with dementia risk in people with type 2 diabetes.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. HIGHLIGHTS: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A1c (HbA1c) variability and dementia risk. Greater HbA1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA1c concentrations

Cognitive Change in a Diverse Group of Individuals Aged 90+: The LifeAfter90 Study

Abstract: Background: The oldest‐old are the fastest growing segment of the elderly population but very little is known about cognition in this age group; particularly in diverse populations. Our goal was to evaluate if domain specific cognitive change was different across different ethnoracial groups in those aged 90+. Method: LifeAfter90 (LA90) is an ongoing cohort of participants aged 90+ who are long‐term members of Kaiser Permanente Northern California participants. Participants (n = 984) were interviewed every 6 months for up to 3.5 years (1‐7 visits). Executive Function (EF) and Verbal Episodic Memory (VEM) were measured every six months using z‐standardized Spanish English Neuropsychological Assessment Scale. Racial/ethnic identify (Asian, Black, Latino, or White participants) was used in linear mixed models with random slopes and intercepts adjusting for baseline age, gender, education, interview mode, and practice effects. Result: Participants were 20% Latino, 23% Black, 24% Asian, 27% White, and 7% other individuals with a mean age of 92.4 (SD = 2.3) and a mean follow up time 1.1 years (Table 1). 39% of the cohort were men, 35% were college educated, and 29% were high school or less educated. Average annual change in EF was ‐0.06 (95% CI: ‐0.12, ‐0.00). Stratified models with Latino as the reference group showed White participants had significantly greater decline in EF (β = ‐0.13; 95%CI:‐0.20,‐0.06), followed by Asian participants (β = ‐0.09; 95%CI:‐0.17,‐0.01). EF scores among Black participants and participants who identified as other declined at a similar rate as Latino participants (β = ‐0.03; 95%CI:‐0.11,‐0.05; β = 0.00; 95%CI:‐0.10, 0.11; respectively) (Table 2: model 2). VEM had an annual change of ‐0.26 (95%CI: ‐0.40, ‐0.13), but there were no significant differences across ethnoracial groups in rate of decline. Conclusion: In this population of individuals aged 90+, decline in EF over the study period varied across ethnoracial group with White participants experiencing the fastest decline and Black, Latino, and other participants experiencing the slowest decline. Continued follow up will identify if there are differences in risk of cognitive impairment in this diverse population of oldest‐old. The results suggest the disparities in cognitive aging for those aged 90+ don’t mirror disparities seen in younger‐elderly ages

Life course financial mobility and later-life memory function and decline by gender, and race and ethnicity: an intersectional analysis of the US KHANDLE and STAR cohort studies

BackgroundIntersectionality has rarely been considered in research studies of cognitive ageing. We investigated whether life-course financial mobility is differentially associated with later-life memory function and decline across intersectional identities defined by gender, and race and ethnicity.MethodsData were from two harmonised multiethnic cohorts (the Kaiser Healthy Aging and Diverse Life Experiences cohort and the Study of Healthy Aging in African Americans cohort) in northern California, USA (n=2340). Life-course financial mobility, measured using a combination of self-reported financial capital measures in childhood (from birth to age 16 years) and later adulthood (at the cohort baseline) was defined as consistently high, upwardly mobile, downwardly mobile, or consistently low. We clustered individuals into 32 strata representing intersectional identities defined by life-course financial mobility combined with gender, and race and ethnicity. Verbal episodic memory was assessed using the Spanish and English Neuropsychological Assessment Scales over four waves from 2017 to 2023. Adjusted mixed-effects linear regression models were estimated with and without fixed effects of gender, race and ethnicity, and financial mobility, to evaluate whether the random effects of the intersectional identity strata contributed variance to memory beyond individual fixed effects.FindingsMean age was 73·6 years (SD 8·1). Of 2340 individuals, 1460 (62·4%) were women, 880 (37·6%) were men, 388 (16·6%) were Asian, 1136 (48·5%) were Black, 334 (14·3%) were Latinx, and 482 (20·6%) were White. Consistently low and downwardly mobile financial capital were strongly negatively associated with later-life memory at baseline (-0·162 SD units [95% CI -0·273 to -0·051] for consistently low and -0·171 [-0·250 to -0·092] for downwardly mobile), but not rate of change over time. Intersectional identities contributed 0·2% of memory variance after accounting for the fixed effects of gender, race and ethnicity, and financial mobility.InterpretationConsistently low and downward life-course financial mobility are associated with lower later-life memory function. Intersectional identities defined by financial mobility in addition to gender, and race and ethnicity, contribute negligible additional variance to later-life memory in this study setting.FundingUS National Institute on Aging, US National Institutes of Health