The Effect of Diabetes Medication on Cognitive Function: Evidence from the PATH Through Life Study

Objective. To examine the effect of diabetes treatment on change of measures of specific cognitive domains over 4 years. Research Design and Methods. The sample was drawn from a population-based cohort study in Australia (the PATH Through Life Study) and comprised 1814 individuals aged 65-69 years at first measurement, of whom 211 were diagnosed with diabetes. Cognitive function was measured using 10 neuropsychological tests. The effect of type of diabetes treatment (diet, oral hypoglycemic agents, and insulin) on measures of specific cognitive domains was assessed using Generalized Linear Models adjusted for age, sex, education, smoking, physical activity level, BMI, and hypertension. Results. Comparison of cognitive function between diabetes treatment groups showed no significant effect of type of pharmacological treatment on cognitive function compared to diet only group or no diabetes group. Of those on oral hypoglycaemic treatment only, participants who used metformin alone had better cognitive function at baseline for the domains of verbal learning, working memory, and executive function compared to participants on other forms of diabetic treatment. Conclusion. This study did not observe significant effect from type of pharmacological treatment for diabetes on cognitive function except that participants who only used metformin showed significant protective effect from metformin on domain of verbal learning, working memory, and executive function.The PATH Through Life Study was funded by National Health and Medical Research Council (NHMRC) Grants (973302, 179805, and 350833). Kaarin J. Anstey and Nicolas Cherbuin were supported by NHMRC Fellowships (002560 and 1063907, resp.). Pushpani M. Herath was supported by Australian National University International Student Scholarship and Australian Research Council Centre for Excellence in Population Ageing Research (CEPAR)

Association of cognitive function with glucose tolerance and trajectories of glucose tolerance over 12 years in the AusDiab study

INTRODUCTION: We investigated the association between glucose tolerance status and trajectories of change in blood glucose, and cognitive function in adults aged 25 to 85. METHODS: The sample (n = 4547) was drawn from a national, population-based cohort study in Australia (AusDiab). Fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and general health were assessed at 0, 5 and 12 years. Covariates included age, education, body mass index, blood pressure and physical activity. At 12 years, participants completed assessments of memory, processing speed and verbal ability. RESULTS: Known diabetes at baseline was associated with slower processing speed at 12 years in both younger (25–59 years) and older (>60 years) age-groups. After 12 years of follow-up, adults aged < 60 with diabetes at baseline had a mean speed score of 49.17 (SE = 1.09) compared with 52.39 (SE = 0.20) in normals. Among younger males without diagnosed diabetes, reduced memory at 12 years was associated with higher HbA1c at 5 years (β = −0.91, SE = 0.26, p < 0.001). No effects were apparent for females or older males. Adjusting for insulin sensitivity (HOMA-%S) and hs-C reactive protein attenuated these associations, but depression and CVD risk did not. Latent class analysis was used to analyse the associations between trajectories of HbA1C and glucose over 12 years, and cognition. Identified classes were described as 1) normal and stable blood glucose over time (reference), 2) high intercept but stable blood glucose over time, and 3) increasing blood glucose over time. In both young males and females, high stable glucose measures were associated with poorer cognitive function after 12 years. CONCLUSIONS: Those with type 2 diabetes, younger males with high non-diabetic HbA1c, and adults with high stable blood glucose are at increased risk of poorer cognition. The findings reinforce the need for management of diabetes risk factors in midlife.For funding or logistical support, the authors are grateful to the National Health and Medical Research Council (NHMRC grants 233200 and 1007544), the Australian Government Department of Health and Ageing, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, Amgen Australia, AstraZeneca, Bristol-Myers Squibb, City Health Centre—Diabetes Service—Canberra, Department of Health and Community Services—Northern Territory, Department of Health and Human Services—Tasmania, Department of Health—New South Wales, Department of Health—Western Australia, Department of Health—South Australia, Department of Human Services— Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd, Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, sanofi-synthelabo, and the Victorian Government’s OIS Program. KJA is funded by NHMRC Research Fellowship No. 1002560. JES is funded by NHMRC Research Fellowship No. 586623

Long-term cognitive correlates of traumatic brain injury across adulthood and interactions with APOE genotype, sex, and age cohorts.

There is continuing debate about long-term effects of brain injury. We examined a range of traumatic brain injury (TBI) variables (TBI history, severity, frequency, and age of injury) as predictors of cognitive outcome over 8 years in an adult population, and interactions with apolipoprotein E (APOE) genotype, sex, and age cohorts. Three randomly sampled age cohorts (20-24, 40-44, 60-64 years at baseline; N = 6333) were each evaluated three times over 8 years. TBI variables, based on self-report, were separately modeled as predictors of cognitive performance using linear mixed effects models. TBI predicted longitudinal cognitive decline in all three age groups. APOE ε4 + genotypes in the young and middle-aged groups predicted lower baseline cognitive performance in the context of TBI. Baseline cognitive performance was better for young females than males but this pattern reversed in middle age and old age. The findings suggest TBI history is associated with long-term cognitive impairment and decline across the adult lifespan. A role for APOE genotype was apparent in the younger cohorts but there was no evidence that it is associated with impairment in early old age. The effect of sex and TBI on cognition varied with age cohort, consistent with a proposed neuroprotective role for estrogen

The impact of mild cognitive impairment on decision-making under explicit risk conditions: Evidence from the Personality and Total Health (PATH) Through Life longitudinal study

Objective: Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults. Method: Data from 245 older adult participants (aged 72-78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests. Results: Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting). Conclusion: MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes

Development and Concurrent Validity of the Short-Form CogDrisk Dementia Risk Assessment Tool

Evidence-based dementia risk assessment is required to inform individual and policy-level dementia risk reduction interventions. We developed the CogDrisk Short Form (CogDrisk-SF) to assess dementia risk factors, for situations where time and resources are limited. To evaluate concurrent validity with the original CogDrisk, we conducted an online survey using a repeated-measures, counterbalanced design. Community dwelling participants (n = 647, 50.1% were female, mean age 62.2 years, age range 40–89) completed the survey. The mean(sd) score for CogDrisk-SF and the CogDrisk was 9.7 (5.3) and 9.9 (5.5), respectively. The intraclass correlation between the risk score obtained from CogDrisk and CogDrisk-SF was 0.92. Fish intake, insomnia and depression had percentage agreements of 79%, 87% and 89% respectively. Other items had >95% agreement except for loneliness (94%), hypertension (94%), cholesterol (93%), atrial fibrillation (91%) and cognitive activity (90%). Very high agreement between the CogDrisk-SF and original CogDrisk shows that CogDrisk-SF is valid for use in research and clinical practice

A longitudinal examination of the relationship between cannabis use and cognitive function in mid-life adults

Background: The relationship between cannabis use and cognitive function in mid-life has rarely been examined despite verbal learning deficits in young adults. Method: A longitudinal cohort study of 1,897 Australians recruited at 40–46 years of age and followed up 4 years (94%) and 8 years (87%) later. Random effects regression was used to assess within- and between-person associations between cannabis use and cognitive function across waves of data, and examine whether age-related changes in cognitive performance were modified by cannabis use. The first list of the California Verbal Learning Test (immediate and delayed recall), Symbol Digit Modality Test, Digit Backwards, simple and choice reaction time tasks, were administered at each wave. The Spot-the-Word test was used to assess premorbid verbal ability. Self-reported cannabis use in the past year (no use, < weekly use, ≥ weekly use) was assessed at each wave. Findings: Participants who used cannabis ≥ weekly had worse immediate recall (b = −0.68, p = 0.014) and showed a trend toward worse delayed recall (b = −0.55, p = 0.062) compared to non-users after adjusting for correlates of cannabis use and premorbid verbal ability. These effects were due to between-person differences. There were no significant within-person associations between cannabis use and recall, nor was there evidence of greater cognitive decline in cannabis users with age. Conclusions: Mid-life cannabis users had poorer verbal recall than non-users, but this was not related to their current level of cannabis use, and cannabis use was not associated with accelerated cognitive decline

A Scoping Survey to Inform Design of Digital Dementia Risk Reduction Interventions for Adults Concerned about their Cognitive Health

Background: Digital dementia risk reduction interventions are cost-effective and scalable. However, it is unknown how they are perceived by people already experiencing cognitive concerns or decline. Objective: To understand the current use, interest, and preferences for online learning courses and interest in learning about factors influencing brain health and dementia risk among adults ≥45. To explore potential differences between individuals experiencing cognitive concerns and those without. Methods: Adults aged 45 and older completed a survey on technology use and healthy ageing (n = 249, Mean age = 65.6, 76.3% female). The Memory Assessment Clinic-Questionnaire was used to assess subjective memory decline, and 153 participants met the study criteria for cognitive concerns (≥25). Results: Almost all participants (98.4%) reported using two or more digital devices, and 51.8% reported increasing device usage following COVID-19. Most (92.1%) were interested in learning about healthy living and memory within an online course, and over 80% indicated a high interest in learning about dementia risk factors. People with cognitive concerns were more likely to report using a 'routine or system' to aid memory than people without (82.4% versus 62.9%, p = 0.001). However, no significant difference was found in technology use, course preferences, or interest in learning about different risk factors. Conclusions: We conclude that adults 45 years and over are interested in online methods for learning about brain health and offer unique insights into adapting dementia prevention programs for cognitive concerns

Development of the CogDrisk tool to assess risk factors for dementia

Introduction: We aimed to develop a comprehensive risk assessment tool for Alzheimer's disease (AD), vascular dementia (VaD), and any dementia, that will be applicable in high and low resource settings. Method: Risk factors which can easily be assessed in most settings, and their effect sizes, were identified from an umbrella review, or estimated using meta-analysis where new data were available. Results: Seventeen risk/protective factors met criteria for the algorithm to estimate risk for any dementia including age, sex, education, hypertension, midlife obesity, midlife high cholesterol, diabetes, insufficient physical activity, depression, traumatic brain injury, atrial fibrillation, smoking, social engagement, cognitive engagement, fish consumption (diet), stroke, and insomnia. A version for AD excluded atrial fibrillation and insomnia due to insufficient evidence and included pesticide exposure. There was insufficient evidence for a VaD risk score. Discussion: Validation of the tool on external datasets is planned. The assessment tool will assist with implementing risk reduction guidelines