Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

The Effects of Cognitive Ability, Mental Health, and Self-Quarantining on Functional Ability of Older Adults During the COVID-19 Pandemic: Results From the Canadian Longitudinal Study on Aging.

OBJECTIVES: Determine whether levels of anxiety and depression, cognitive ability, and self-quarantining during and prior to the pandemic predict decreases in perceived functional ability. DESIGN AND SETTING: Longitudinal data collected from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study (2020) and core CLSA study (Follow-Up 1; 2014-2018). PARTICIPANTS: 17 541 CLSA participants. MEASUREMENTS: Self-quarantining behaviours from questionnaires administered at Baseline (April 2020), Monthly, and Exit (December 2020) time points of the CLSA COVID-19 Questionnaire Study, levels of anxiety and depression at Baseline, perceived change in functional ability at Exit, and performance on neuropsychological tests (Rey Auditory Verbal Learning Task, Mental Alternation Task, Animal Fluency Test) and functional ability (Older Americans Resources and Services [OARS] Multidimensional Assessment Questionnaire) from the core CLSA study. RESULTS: Greater cognitive ability pre-pandemic (B = -.003, P < .01), higher levels of anxiety (B = -.024, P < .01) and depressive symptoms (B = -.110, P < .01) at Baseline, and higher frequency of engaging in self-quarantining throughout the COVID-19 survey period (B = -.098, P < .01) were associated with perceived loss in functional ability at Exit. Self-quarantining behaviour was associated with perceived loss in functional ability only at average and high levels of depressive symptoms (B = -.013, P < .01). CONCLUSIONS: Older adults with higher cognitive and lower functional ability prior to the pandemic were at greater risk of decreased perceived functional ability during the first year of the pandemic, as were those who experienced greater levels of anxiety and depressive symptoms during the pandemic. Strategies/interventions to preserve functional ability in older adults with cognitive independence prior to future pandemics are warranted.

The impact of loneliness and social isolation during COVID-19 on cognition in older adults: a scoping review.

Background: The COVID-19 pandemic required implementation of public health measures to reduce the spread of SARS CoV-2. This resulted in social isolation and loneliness for many older adults. Loneliness and social isolation are associated with cognitive decline, however, the impact of this during COVID-19 has not been fully characterized. Objective: The aim of this scoping review was to explore the impact of social isolation and loneliness during COVID-19 on cognition in older adults. Eligibility criteria: Eligible studies occurred during the COVID-19 pandemic, enrolled older adults and reported longitudinal quantitative data on both loneliness (exposure) and cognition (outcome). Sources of evidence: A comprehensive search was conducted in CINAHL, Medline, PubMed, and Psychinfo databases (updated October 10, 2023). Charting methods: Studies were screened independently by two reviewers and study characteristics, including participant demographics, loneliness and cognition measurement tools, study objectives, methods and results were extracted. Results: The search yielded 415 results, and seven were included in the final data synthesis. All studies were conducted between 2019 and 2023. Six studies enrolled community-dwelling individuals while the remaining study was conducted in long-term care. In 6 studies, loneliness and/or social isolation was correlated with poorer cognitive function. In the seventh study, subjective memory worsened, while objective cognitive testing did not. Conclusion: Loneliness and social isolation during COVID-19 were correlated with cognitive decline in older adults. The long-term effect of these impacts remains to be shown. Future studies may focus on interventions to mitigate the effects of loneliness and social isolation during future pandemics.

COVID-19 vaccine uptake among people with HIV: identifying characteristics associated with vaccine hesitancy.

People with HIV (PWH) are at increased risk of COVID-19 infection. Both Canadian (NACI) and US (CDC) guidelines recommend that all PWH receive at least 2 doses of COVID-19 vaccine, and a booster. We examined vaccination uptake among PWH in Southern Alberta, Canada. Among adult PWH, we evaluated COVID-19 vaccination uptake between December 2020 and August 2022. Poisson regression models with robust variance (approximating log binomial models) estimated crude and adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for receiving (1) any vs. no vaccine, and (2) primary series with booster (≥ 3 vaccines) versus primary series without booster. Among 1885 PWH, 10% received no COVID-19 vaccinations, 37% < 3 vaccines and 54% received ≥ 3 vaccines. Females (vs. males) were less likely to receive a vaccine booster. Receiving no COVID-19 vaccines was associated with White ethnicity, unsuppressed HIV viral load (> 200 copies/mL), and using illegal substances. Factors associated with decreased booster uptake included being younger, Black (vs. White) ethnicity, substance use, lower educational attainment, and having an unsuppressed HIV viral load. COVID-19 booster uptake among PWH does not meet vaccine guidelines, and receipt of vaccines is unevenly distributed. Booster uptake is lowest among young females and marginalized individuals. Focused outreach is necessary to close this gap.

Baseline characteristics of a prospective cohort study of aging and cardiovascular diseases among people living with HIV.

OBJECTIVES: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol. METHODS: CHACS is a multi-centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow-up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender-gender roles, gender identity, gender relationships, and institutionalized gender-will be measured using the GENESIS-PRAXY questionnaire. Diet will be assessed using a validated, web-based, self-administered food frequency questionnaire. RESULTS: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50-61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail. CONCLUSIONS: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio-economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses.

Pneumococcal vaccination uptake and missed opportunities for vaccination among Canadian adults: A cross-sectional analysis of the Canadian Longitudinal Study on Aging (CLSA).

INTRODUCTION: In Canada, pneumococcal vaccination is recommended to all adults aged ≥65 and those <65 who have one or more chronic medical conditions (CMCs). Understanding vaccine uptake and its determinants among eligible groups has important implications for reducing the burden of pneumococcal disease. METHODS: Using data from a large national cohort of Canadian residents aged ≥47 years between 2015-2018, we calculated self-reported pneumococcal vaccine uptake among eligible groups, estimated associations between key factors and non-vaccination, assessed missed opportunities for vaccination (MOV) and examined risk factors for MOV. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for relevant associations were estimated through logistic regression. RESULTS: 45.8% (95% CI: 45.2-46.5) of 22,246 participants aged ≥65 and 81.3% (95% CI: 80.5-82.0) of 10,815 individuals aged 47-64 with ≥1 CMC reported never having received a pneumococcal vaccine. Receipt of influenza vaccination in the previous year was associated with the lowest odds of pneumococcal non-vaccination (aOR = 0.14 [95% CI: 0.13-0.15] for older adults and aOR = 0.23 [95% CI: 0.20-0.26] for those aged 47-64 with ≥1 CMC). Pneumococcal vaccine uptake was also more likely in case of contact with a family doctor in the previous year (versus no contact), increased with age and varied widely across provinces. Among individuals recently vaccinated against influenza, 32.6% (95% CI: 31.9-33.4) of those aged ≥65 and 71.1% (95% CI: 69.9-72.3) of those aged 47-64 with ≥1 CMC missed an opportunity to get a pneumococcal vaccine. Among individuals who had contact with a family doctor, 44.8% (95% CI: 44.1-45.5) of those aged ≥65 and 80.4% (95% CI: 79.6-81.2) of those aged 47-64 with ≥1 CMC experienced a MOV. CONCLUSIONS: Pneumococcal vaccine uptake remains suboptimal among at-risk Canadian adults who are eligible for vaccination. Further research is needed to clarify the reasons behind missed opportunities for vaccination and adequately address the main barriers to pneumococcal vaccination.

Can "Rover" help with mental health during the COVID-19 pandemic? Results from the Canadian Longitudinal Study on Aging (CLSA).

COVID-19 has negatively affected the mental health and well-being of adults, and thus it is important to examine potential factors which may influence mental health during the pandemic. We thus examined the association between pet ownership and depression/anxiety symptoms based on mental health disorder status during the COVID-19 pandemic. We included 12,068 cognitively healthy participants (45-86 years at study entry) from the Canadian Longitudinal Study on Aging (CLSA) comprehensive cohort who completed the first follow-up ([FU1]; 2015-2018), and COVID-19 Survey entry (April-May 2020) and exit (September-December 2020). Participants self-reported at FU1 if they owned a pet (yes/no). Participants were dichotomized as with or without a mental health disorder based on self-reported diagnosis of depression, anxiety, or mood disorders at baseline assessment (2011-2015) or FU1. Depressive symptoms were indexed using the 10-item Center for Epidemiological Studies Depression Scale (CESD-10) at FU1, and COVID-19 entry/exit surveys. Anxiety symptoms were assessed using the General Anxiety Disorder Questionnaire (GAD-7) at COVID-19 entry/exit surveys. Final models adjusted for age, sex, body mass index, income, education, living status, smoking status, relationship status, and alcohol intake. Forty-percent of participants owned a pet at FU1. Among those without a mental health disorder, there were no significant differences in CESD-10 between participants who owned pets compared with those without pets. For people with a mental health disorder, pet owners had higher CESD-10 (estimated mean difference range: 0.56-1.02 points; p < 0.05) and GAD-7 scores (estimated mean difference range: 0.28-0.57 points; p < 0.05) at both COVID-19 entry and exit surveys. Among people with mental health disorders, pet ownership was associated with poor mental health symptoms during April 2020 to December 2020 of the COVID-19 pandemic.

Predictors of reported alcohol intake during the first and second waves of the COVID-19 pandemic in Canada among middle-aged and older adults: results from the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: To examine proportions and predictors of change in alcohol intake and binge drinking during the first 2 waves of the COVID-19 pandemic among middle-aged and older participants in the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study. METHODS: A total of 28,559 (67.2% of the potential sample) CLSA participants consented to the study with 24,114 completing the exit survey (fall 2020). Descriptive statistics and logistic regressions to examine predictors of change (increase or decrease) in alcohol intake and binge drinking were performed. RESULTS: Among alcohol users, 26.3% reported a change in alcohol consumption during the first 10 months of the pandemic. Similar percentages increased (13.0%) or decreased (13.3%) consumption. In our mutually adjusted logistic regression model, odds of change in alcohol intake were greater for younger age, higher income, current cannabis smoker, positive screen for depression, anxiety, and loneliness. The magnitude of all associations for decreased intake was less than that of increased intake, and the directions were opposite for male sex and age. Predictors of current binge drinking (27.9% of alcohol users) included male sex, younger age, higher education and income, cannabis use, depression, and anxiety. CONCLUSION: Factors predictive of potentially worrisome alcohol use (i.e. increased intake, binge drinking) included younger age, sex, greater education and income, living alone, cannabis use, and worse mental health. Some of these factors were also associated with decreased intake, but the magnitudes of associations were smaller. This information may help direct screening efforts and interventions towards individuals at risk for problematic alcohol intake during the pandemic.

RéSUMé: OBJECTIF: Examiner les proportions et les prédicteurs des changements dans la consommation d'alcool et l'hyperalcoolisation rapide au cours des deux premières vagues de la pandémie de COVID-19 chez les personnes âgées et d'âge moyen ayant participé à l'étude par questionnaire sur la COVID-19 de l'Étude longitudinale canadienne sur le vieillissement (ELCV). MéTHODE: Un total de 28 559 participants de l'ELCV (67,2 % de l'échantillon potentiel) ont consenti à l'étude sur la COVID-19, et 24 114 ont répondu à l'enquête à la sortie (automne 2020). Nous avons procédé par statistique descriptive et par régression logistique pour examiner les prédicteurs des changements (augmentation ou diminution) dans la consommation d'alcool et l'hyperalcoolisation rapide. RéSULTATS: Chez les consommateurs d'alcool, 26,3 % ont déclaré un changement de leur consommation d'alcool au cours des 10 premiers mois de la pandémie. Un pourcentage semblable de consommateurs d'alcool avaient accru (13 %) ou diminué (13,3 %) leur consommation. Dans notre modèle de régression logistique mutuellement ajusté, la probabilité de changement dans la consommation d'alcool était plus élevée chez les répondants plus jeunes, les répondants au revenu élevé, les fumeurs de cannabis actuels et les répondants ayant fait état de dépression, d'anxiété ou de solitude. Les associations avec la diminution de la consommation étaient moins significatives qu'avec l'augmentation de la consommation, et elles allaient dans le sens opposé pour ce qui est du sexe masculin et de l'âge. Les prédicteurs de l'hyperalcoolisation rapide actuelle (27,9 % des consommateurs d'alcool) étaient le sexe masculin, l'âge plus jeune, l'instruction et le revenu élevés, la consommation de cannabis, la dépression et l'anxiété. CONCLUSION: Les facteurs pouvant prédire une consommation d'alcool potentiellement inquiétante (c.-à-d. consommation accrue, hyperalcoolisation rapide) étaient l'âge plus jeune, le sexe, l'instruction et le revenu élevés, le fait de vivre seul, la consommation de cannabis et la moins bonne santé mentale. Certains de ces facteurs étaient aussi associés à une consommation réduite, mais ces associations étaient moins significatives. Ces informations pourraient orienter les efforts de dépistage et les interventions auprès des personnes à risque de consommation problématique d'alcool durant la pandémie.

Assessment and Management of Older Patients With Transthyretin Amyloidosis Cardiomyopathy: Geriatric Cardiology, Frailty Assessment and Beyond.

Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is commonly diagnosed in older adults, in particular the wild-type (ATTRwt), which is regarded as an age-related disease. With an aging population and improved diagnostic techniques, the prevalence and incidence of ATTR-CM will continue to increase. With increased availability of mortality reducing ATTR-CM therapies, patients are living longer. The predominant clinical manifestation of ATTR-CM is heart failure, while other cardiovascular manifestations include arrhythmia and aortic stenosis. Given their older age at diagnosis, patients often present with multiple age-related comorbidities, some of which can be exacerbated by ATTR, including neurologic, musculoskeletal, and gastrointestinal problems. Considerations related to older patient care, such as frailty, cognitive decline, polypharmacy, falls/mobility, functional capacity, caregiver support, living environment, quality of life and establishing goals of care are particularly important for many patients with ATTR-CM. Furthermore, the high cost ATTR treatments has increased interest in establishing improved predictors of response to therapy, with assessment of frailty emerging as a potentially important determinant. Multidisciplinary care inclusive of collaboration with geriatric and elder care medicine specialists, and others such as neurology, orthopedic surgery, electrophysiology and transcatheter aortic valve replacement clinics, is now an important component of ATTR-CM management. This review will examine current aspects of the management of older ATTR-CM patients, including shared care with multiple medical specialists, the emerging importance of frailty assessment and other considerations for using ATTR therapies.

Factors Associated With Willingness to Receive a COVID-19 Vaccine Among 23,819 Adults Aged 50 Years or Older: An Analysis of the Canadian Longitudinal Study on Aging.

Identifying persons who are least willing to receive a coronavirus disease 2019 (COVID-19) vaccine is critical for increasing uptake via targeted outreach. We conducted a survey of 23,819 Canadian Longitudinal Study on Aging participants from September 29 to December 29, 2020, to assess factors associated with COVID-19 vaccination willingness and reasons for willingness or lack thereof. Among adults aged 50-96 years, 84.1% (95% confidence interval (CI): 83.7, 84.6) were very or somewhat willing to receive a COVID-19 vaccine; 15.9% (95% CI: 15.4, 16.3) were uncertain or very or somewhat unwilling. Based on logistic regression, those who were younger, female, had lower education and income, were non-White, and lived in a rural area were less willing to receive a COVID-19 vaccine. After controlling for these factors, recent receipt of influenza vaccine (adjusted odds ratio = 14.3, 95% CI: 12.5, 16.2) or planning to receive influenza vaccine (adjusted odds ratio = 10.5, 95% CI: 9.5, 11.6), as compared with no receipt or planning, was most strongly associated with COVID-19 vaccination willingness. Willingness was also associated with believing one had never been infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and experiencing negative pandemic consequences. Safety concerns were most common among those unwilling. Our comprehensive assessment of COVID-19 vaccination willingness among older adults in Canada, a prioritized group for vaccination due to their risk of severe COVID-19 outcomes, provides a road map for conducting outreach to increase uptake, which is urgently needed.

Frailty in Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Frailty and Parkinson's disease (PD) are common conditions that increase with age. Independently, frailty and PD lead to increased morbidity and mortality for patients. Few studies report on frailty in patients with PD. We performed a systematic review and meta-analysis of the prevalence, associations and outcomes of frailty in persons with PD. METHODS: We searched four electronic databases and grey literature from inception to May 19, 2020, for articles which reported the prevalence, associations and outcomes of frailty in persons with PD. RESULTS: One-thousand and sixty-three citations were identified, of which 127 articles were reviewed. Thirty studies were included. Twenty-eight studies were observational and the settings varied including 25 community and 5 inpatient studies.The most common frailty screening measures were the frailty phenotype and clinical frailty scale. The prevalence of frailty in PD using the FP was 0.38 (0.24-0.55) with I2 = 92.6% (p < 0.01). Frailty was associated with recurrent falls, cognitive impairment, dementia, orthostatic hypotension, fatigue, hallucinations, nursing home placement, dependency in activities of daily living and in-patient mortality. PD disease duration, motor impairment, non-tremor dominant PD (postural instability/gait difficulty dominant phenotype) and total daily levodopa dose were associated with frailty. CONCLUSION: Frailty is common in PD. There is no agreed upon tool for identifying frailty, however, the importance of its identification is apparent given the high prevalence and the association between frailty and adverse outcomes in persons with PD. Future studies are required to guide clinicians in how best to identify and manage frail patients with PD.

Construct and Criterion-Related Validity of the Clinical Frailty Scale in Persons With HIV.

BACKGROUND: The co-occurrence of frailty and cognitive impairment in older (50+ years) persons with HIV (PWH) is common and increases the risk of poor outcomes. In HIV clinics, the most commonly used frailty measures are the frailty phenotype (FP), which requires measuring grip strength and gait speed to implement, and the frailty index (FI) based on comprehensive health data collected on patients. We examined construct and criterion-related validity (as it predicts cognition) of the Clinical Frailty Scale (CFS), a less resource-intensive approach for assessing frailty, in relation to these more commonly used frailty assessments (FP and FI). SETTING/METHODS: A total of 143 older (age 50+) PWH (mean age 57 years; 88% male) seen at the Southern Alberta Clinic underwent both frailty screening with the FP, CFS, and FI and neuropsychological testing. Mixed-effects regressions examined the associations between frailty status and cognition. RESULTS: Concordance with the FP was slightly superior for the CFS than the FI. The FP and CFS had similar associations with domain-specific cognitive performance with frail PWH performing worse than nonfrail individuals on tests requiring manual dexterity (Trail Making Part A and B; Symbol Digit; and Grooved Pegboard; P values <0.05). Neither were associated with executive function, learning, or memory performance. The FI was associated with worse fluency, fine motor skills (Grooved Pegboard), and Trail Making Part A. CONCLUSION: The CFS is a simple screening tool with good construct and criterion-related validity. It was associated with a similar pattern of cognitive deficits as the FP. If confirmed and the associations are extended to other clinically significant characteristics and outcomes, the CFS can be considered as an alternative to the FP and FI in assessing frailty in older PWH.

Comorbidities in Older Persons with Controlled HIV Infection: Correlations with Frailty Index Subtypes.

Frailty is prevalent in persons with human immunodeficiency virus (PWH), but factors predisposing older PWH to frailty remain uncertain. We examined factors associated with frailty and determined whether there were multiple frailty subtypes in older adults with controlled HIV infection. This was a cross-sectional outpatient study in an urban HIV clinic. Twenty-nine clinical indicators were extracted from medical records to compute a Frailty Index (FI) for 389 older (age 50+) PWH (range = 50-93; mean = 61.1, standard deviation = 7.2; 85% men) receiving HIV treatment in Calgary, Canada. We used regressions to identify factors associated with FI values. Latent class analysis was used to identify FI subtypes. Age, employment status, and duration of known HIV infection were the strongest predictors of FI (p's < 0.05). Four FI subtypes were identified. Subtype 1 (severe metabolic dysfunction+polypharmacy) had the highest mean FI (0.30). Subtype 2 (less severe metabolic dysfunction+polypharmacy) and Subtype 3 (lung and liver dysfunction+polypharmacy) had lower but equivalent mean FIs (0.20 for each). Subtype 4 (least severe metabolic dysfunction) had the lowest mean FI (0.13; p's < 0.001). Sociodemographic and behavioral characteristics differed among the subtypes. Individuals with Subtype 1 were older and more frequently unemployed/retired, whereas those with Subtype 3 were more likely to smoke, use crack/cocaine, have heavy alcohol use, and live in temporary/unstable housing. The clinical presentation of frailty in older PWH is heterogeneous. The metabolic syndrome, hepatitis C virus coinfection, cirrhosis, lung disease, and polypharmacy were associated with frailty as were unemployment/retirement, unstable housing, and substance use.

An Emerging Concern-High Rates of Frailty among Middle-aged and Older Individuals Living with HIV.

BACKGROUND: The aim of the present study was to calculate a frailty index (FI) in older adults (≥50) living with HIV, search for cross-sectional associations with the FI, and investigate the association between the FI score and two-year mortality. METHODS: Cross-sectional study with a short-term prospective component for the determination of two-year mortality was performed. The study took place in an HIV outpatient clinic in Calgary, Canada between November 1, 2016 and December 31, 2018. Over 700 patients 50 years of age or older took part. We calculated a FI for each patient, examined associations between FI and select patient characteristics, and evaluated the association between FI value and two-year mortality. RESULTS: The mean FI was 0.303 (± 0.128). Mean FI did not differ between males and females, nor was it associated with either nadir or current CD4 cell count. It did increase with age, duration of ART, and duration of diagnosed HIV infection. Mean FI was higher among those who died compared to survivors (0.351 vs. 0.301; p=.033). CONCLUSIONS: Frailty is highly prevalent in persons living with HIV and associated with a higher mortality rate. Health-care providers should be aware of the earlier occurrence of frailty in adults living with HIV.

Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis.

BACKGROUND: The association between diabetes mellitus (DM) treatment and dementia is not well understood. OBJECTIVE: To investigate the association between treatment of diabetes, hypoglycemia, and dementia risk. RESEARCH DESIGN AND METHODS: We performed a systematic review and meta-analysis of pharmacological treatment of diabetes and incident or progressive cognitive impairment. We searched Ovid MEDLINE, Embase, Cochrane Central Registry of Controlled Trials, and PsychINFO from inception to 18 October 2017. We included cross-sectional, case-control, cohort, and randomized controlled studies. The study was registered with PROSPERO (ID CRD42017077953). RESULTS: We included 37 studies into our systematic review and 13 into our meta-analysis. Ten studies investigated any antidiabetic treatment compared with no treatment or as add-on therapy to prior care. Treatment with an antidiabetic agent, in general, was not associated with incident dementia (risk ratio (RR) 1.01; 95% CI 0.93 to 1.10). However, we found differential effects across drug classes, with a signal of harm associated with insulin therapy (RR 1.21; 95% CI 1.06 to 1.39), but potentially protective effects with thiazolidinedione exposure (RR 0.71; 95% CI 0.55 to 0.93). Severe hypoglycemic episodes were associated with a nearly twofold increased likelihood of incident dementia (RR 1.77; 95% CI 1.35 to 2.33). Most studies did not account for DM duration or severity. CONCLUSIONS AND LIMITATIONS: The association between treatment for diabetes and dementia is differential according to drug class, which is potentially mediated by hypoglycemic risk. Not accounting for DM duration and/or severity is a major limitation in the available evidence base.