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Introduction: Informant reports are a critical component of dementia diagnoses, but the comparability of informant reports across countries is not well understood., Methods: We compared the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) using population-representative surveys in the United States (N = 3183), England (N = 1050), and India (N = 4047)., Results: Analyses of regression splines and comparisons of model fit showed strong associations between IQCODE and objective cognition at low cognitive functioning in the United States and England; in India, the association was weaker but consistent over the range of cognition. Associations between IQCODE score and informant generation (analysis of variance [ANOVA] p = 0.001), caregiver status (p < 0.001), and years known by the informant (p = 0.015) were different across countries after adjusting for objective cognition., Discussion: In India, the IQCODE was less sensitive to impairments at the lowest levels of cognitive functioning. Country-specific adjustments to IQCODE scoring based on informant characteristics may improve cross-national comparisons., Highlights: Associations between IQCODE and cognitive testing were similar in the United States and England but differed in India. In India, the IQCODE may be less sensitive to impairments among those with low cognition and no education. Informant characteristics may differentially impact informant reports of decline across countries. Adjustments or culturally sensitive adaptations may improve cross-national comparability., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Lower Health Related Quality of Life (HRQoL) precedes dementia in older adults in the USA. We explore prospective associations between HRQoL and dementia in British adults in mid and late-life, when interventions to optimise cognitive ageing may provide benefit. 7,452 community-dwelling participants (57% women; mean age 69.3 ± 8.3 years) attended the European Prospective Investigation of Cancer-Norfolk study's third health check (3HC) and reported their HRQoL using Short-Form 36 (SF-36). Cox Proportional Hazard regression models explored associations between standard deviation differences in baseline Physical Component (PCS) and Mental Component Summary (MCS) scores, as well as eight SF-36 sub-scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health), and incident dementia over ten years. Logistic regression models explored cross-sectional relationships at the 3HC between HRQoL and objective global cognitive function (n = 4435; poor cognition = lowest performance decile). The cohort was examined as a whole and by age-group (50-69, ≥ 70), considering socio-demographics and co-morbidity. Higher MCS scores were associated with lower chance of incident dementia (Hazard Ratio [HR] = 0.74, 95% CI 0.68-0.81) and lower odds of poor cognition (Odds Ratio [OR] = 0.82, 0.76-0.89), with findings similar by age-group. Higher PCS scores were not associated with dementia in the whole cohort (HR = 0.93, 0.84-1.04) or considering age-groups; and were only associated with poor cognition in younger participants (OR = 0.81, 0.72-0.92). Similarly, associations between higher scores on subscales pertaining to mental, but not physical, HRQoL and lower dementia incidence were observed. Lower mental HRQoL precedes dementia diagnosis in middle-aged and older British adults., (© 2023. The Author(s).)

Introduction: The measurement of dementia in cross-national contexts relies on the assessment of functional limitations. We aimed to evaluate the performance of survey items on functional limitations across culturally diverse geographic settings., Methods: We used data from the Harmonized Cognitive Assessment Protocol Surveys (HCAP) in five countries (total N = 11,250) to quantify associations between items on functional limitations and cognitive impairment., Results: Many items performed better in the United States and England compared to South Africa, India, and Mexico. Items on the Community Screening Instrument for Dementia (CSID) had the least variability across countries (SD = 0.73 vs. 0.92 [Blessed] and 0.98 [Jorm IQCODE]), but also the weakest associations with cognitive impairment (median odds ratio [OR] = 2.23 vs. 3.01 [Blessed] and 2.75 [Jorm IQCODE])., Discussion: Differences in cultural norms for reporting functional limitations likely influences performance of items on functional limitations and may affect the interpretation of results from substantive studies., Highlights: There was substantial cross-country variation in item performance. Items from the Community Screening Instrument for Dementia (CSID) had less cross-country variability but lower performance. There was more variability in performance of instrumental activities of daily living (IADL) compared to activities of daily living (ADL) items. Variability in cultural expectations of older adults should be taken into account. Results highlight the need for novel approaches to assessing functional limitations., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: To evaluate the characteristics of individuals recorded as having a dementia diagnosis in different routinely collected records and to examine the extent of overlap of dementia coding across data sources. Also, to present comparisons of secondary and primary care records providing value for researchers using routinely collected records for dementia outcome capture., Study Design: A prospective cohort study., Setting and Participants: A cohort of 25 639 men and women in Norfolk, aged 40-79 years at recruitment (1993-1997) followed until 2018 linked to routinely collected to identify dementia cases. Data sources include mortality from death certification and National Health Service (NHS) hospital or secondary care records. Primary care records for a subset of the cohort were also reviewed., Primary Outcome Measure: Diagnosis of dementia (any-cause)., Results: Over 2000 participants (n=2635 individuals) were found to have a dementia diagnosis recorded in one or more of the data sources examined. Limited concordance was observed across the secondary care data sources. We also observed discrepancies with primary care records for the subset and report on potential linkage-related selection bias., Conclusions: Use of different types of record linkage from varying parts of the UK's health system reveals differences in recorded dementia diagnosis, indicating that dementia can be identified to varying extents in different parts of the NHS system. However, there is considerable variation, and limited overlap in those identified. We present potential selection biases that might occur depending on whether cause of death, or primary and secondary care data sources are used. With the expansion of using routinely collected health data, researchers must be aware of these potential biases and inaccuracies, reporting carefully on the likely extent of limitations and challenges of the data sources they use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there is a lack of large studies with objective measures of vision and with more than 10 years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk). In both cohorts, visual acuity was measured using a "logarithm of the minimum angle of resolution" (LogMAR) chart and categorized as no (≤0.30 LogMAR), mild (>0.3 to ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62 206 UK Biobank and 7 337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk, respectively, 1 113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable Cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% confidence interval [CI]: 0.92-1.72) and 2.16 (95% CI: 1.37-3.40), in UK Biobank, and 1.05 (95% CI: 0.72-1.53) and 1.93 (95% CI: 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but was not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention; however, the possibility of reverse causation cannot be excluded., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions., (© 2021. The Author(s).)

Background: Exploring the domains of cognitive function which are most strongly associated with future dementia may help with understanding risk factors for, and the natural history of dementia., Objective: To examine the association of performance on a range of cognitive tests (both global and domain specific) with subsequent diagnosis of dementia through health services in a population of relatively healthy men and women and risk of future dementia., Methods: We examined the association between performance on different cognitive tests as well as a global score and future dementia risk ascertained through health record linkage in a cohort of 8,581 individuals (aged 48-92 years) between 2004-2019 with almost 15 years follow-up (average of 10 years) before and after adjustment for socio-demographic, lifestyle, and health characteristics., Results: Those with poor performance for global cognition (bottom 10%) were almost four times as likely to receive a dementia diagnosis from health services over the next 15 years than those who performed well HR = 3.51 (95% CI 2.61, 4.71 p < 0.001) after adjustment for socioeconomic, lifestyle, and biological factors and also prevalent disease. Poor cognition performance in multiple tests was associated with 10-fold increased risk compared to those not performing poorly in any test HR = 10.82 (95% CI 6.85, 17.10 p < 0.001)., Conclusion: Deficits across multiple cognitive domains substantially increase risk of future dementia over and above neuropsychological test scores ten years prior to a clinical diagnosis. These findings may help further understanding of the natural history of dementia and how such measures could contribute to strengthening future models of dementia.

INTRODUCTION: Informant reports are a critical component of dementia diagnoses, but the comparability of informant reports across countries is not well understood. METHODS: We compared the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) using population‐representative surveys in the United States (N = 3183), England (N = 1050), and India (N = 4047). RESULTS: Analyses of regression splines and comparisons of model fit showed strong associations between IQCODE and objective cognition at low cognitive functioning in the United States and England; in India, the association was weaker but consistent over the range of cognition. Associations between IQCODE score and informant generation (analysis of variance [ANOVA] p = 0.001), caregiver status (p < 0.001), and years known by the informant (p = 0.015) were different across countries after adjusting for objective cognition. DISCUSSION: In India, the IQCODE was less sensitive to impairments at the lowest levels of cognitive functioning. Country‐specific adjustments to IQCODE scoring based on informant characteristics may improve cross‐national comparisons. Highlights: Associations between IQCODE and cognitive testing were similar in the United States and England but differed in India.In India, the IQCODE may be less sensitive to impairments among those with low cognition and no education.Informant characteristics may differentially impact informant reports of decline across countries.Adjustments or culturally sensitive adaptations may improve cross‐national comparability. [ABSTRACT FROM AUTHOR]

Background: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. Objective: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. Methods: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. Results: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82–1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93–1.19]. Gender did not modify any associations under study. Conclusion: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures. [ABSTRACT FROM AUTHOR]

Introduction: The measurement of dementia in cross‐national contexts relies on the assessment of functional limitations. We aimed to evaluate the performance of survey items on functional limitations across culturally diverse geographic settings. Methods: We used data from the Harmonized Cognitive Assessment Protocol Surveys (HCAP) in five countries (total N = 11,250) to quantify associations between items on functional limitations and cognitive impairment. Results: Many items performed better in the United States and England compared to South Africa, India, and Mexico. Items on the Community Screening Instrument for Dementia (CSID) had the least variability across countries (SD = 0.73 vs. 0.92 [Blessed] and 0.98 [Jorm IQCODE]), but also the weakest associations with cognitive impairment (median odds ratio [OR] = 2.23 vs. 3.01 [Blessed] and 2.75 [Jorm IQCODE]). Discussion: Differences in cultural norms for reporting functional limitations likely influences performance of items on functional limitations and may affect the interpretation of results from substantive studies. Highlights: There was substantial cross‐country variation in item performance.Items from the Community Screening Instrument for Dementia (CSID) had less cross‐country variability but lower performance.There was more variability in performance of instrumental activities of daily living (IADL) compared to activities of daily living (ADL) items.Variability in cultural expectations of older adults should be taken into account.Results highlight the need for novel approaches to assessing functional limitations. [ABSTRACT FROM AUTHOR]

Background: The current evidence for higher physical activity and better cognitive function and lower risk of dementia is strong but not conclusive. More robust evidence is needed to inform public-health policy. We provide further insight into discrepancies observed across studies, reporting on habitual inactivity including that during work.Methods: We examined cross-sectional and prospective relationships of physical inactivity during leisure and occupation time, with cognitive performance using a validated physical-activity index in a cohort of 8585 men and women aged 40-79 years at baseline (1993-1997) for different domains using a range of cognitive measures. Cognitive testing was conducted between 2006 and 2011 (including a pilot phase 2004-2006). Associations were examined using multinomial logistic-regression adjusting for socio-demographic and health variables as well total habitual physical activity.Results: Inactivity during work was inversely associated with poor cognitive performance (bottom 10th percentile of a composite cognition score): odds ratio (OR) = 0.68 [95% confidence interval (CI) 0.54, 0.86], P = 0.001. Results were similar cross-sectionally: OR = 0.65 (95% CI 0.45, 0.93), P = 0.02. Manual workers had increased risk of poor performance compared with those with an occupation classified as inactive. Inactivity during leisure time was associated with increased risk of poor performance in the cross-sectional analyses only.Conclusions: The relationship between inactivity and cognition is strongly confounded by education, social class and occupation. Physical activity during leisure may be protective for cognition, but work-related physical activity is not protective. A greater understanding of the mechanisms and confounding underlying these paradoxical findings is needed. [ABSTRACT FROM AUTHOR]