10-year Risk Of Dementia Research Articles

The Associations of Sensory Impairment With 10-Year Risk of Dementia and Alzheimer's Disease: The Health and Retirement Study, 2010-2020.

Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings. To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50. A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. Participants were categorized as having no visual or hearing impairment, visual impairment only, hearing impairment only, and dual sensory impairment. Fine-Gray competing risk regression model was applied to estimate the associations of sensory impairment with incident dementia and Alzheimer's disease, adjusted for demographic characteristics, health behaviors, and health conditions at baseline. Of 20,248 identified individuals, 14.6% had visual impairment only, 11.2% had hearing impairment only, and 9.1% had dual impairment at baseline. After adjusting for all covariates, dual sensory impairment was associated with higher risk of dementia (HR = 1.46, 95% CI: 1.23-1.73) and Alzheimer's disease (HR = 1.35, 95% CI: 1.03-1.76). Visual impairment only was also associated with incident dementia and Alzheimer's disease among individuals <65 years. Older adults in the U.S. with visual and hearing impairments simultaneously had a particularly greater risk of dementia and Alzheimer's disease, indicating the needs of targeted screening for timely treatment and further prevention of dementia and Alzheimer's disease.

Physical Exercise and Health, 6: Sedentary Time, Independent of Health-Related Physical Activity, as a Risk Factor for Dementia in Older Adults.

Sedentary behaviors are leisurely behaviors that occur during waking hours performed while lying down or seated; examples are relaxing, conversing, using a smartphone, watching television, traveling in private or public transport, and thinking or working at a desk. Sedentary behaviors are common in everyday life; the average person spends 9-10 h/d sedentary. Findings from meta-analyses show that higher levels of physical activity are associated with a reduced risk of dementia and that near-absence of moderate to vigorous physical activity is associated with an increased risk of dementia. Sedentariness is a clearly defined construct that is more than just low levels of physical activity. Sedentariness, therefore, merits independent study. In this context, a recent cohort study, conducted in elderly subjects (mean age, 67 years) who were followed for a mean of 6.7 years, found that sedentariness, independent of current levels of moderate to vigorous physical activity, was associated in a dose-dependent fashion with the risk of incident dementia; the finding held true when reverse causation was addressed through the exclusion of subjects who developed dementia within 4 years of follow-up. The adjusted 10-year risk of dementia rose from about 8% with sedentariness at 10 h/d to about 23% with sedentariness at 15 h/d; the difference is clinically meaningful. Limitations of studies in the field are that residual confounding cannot be excluded, and that no randomized controlled trials exist upon which guidance may be based. Nevertheless, it could be prudent to decrease sedentary behaviors if only because these have also been associated with other adverse physical and mental health outcomes. Additional subjects explained in this article include reverse causation and how it may be dealt with during research design and data analysis, individual participant data meta-analysis, and making sense of results that are reported in terms of "per 1,000 person-years."

Disparities in neighbourhood characteristics and 10-year dementia risk by nativity status.

Prior research indicates that neighbourhood disadvantage increases dementia risk. There is, however, inconclusive evidence on the relationship between nativity and cognitive impairment. To our knowledge, our study is the first to analyse how nativity and neighbourhood interact to influence dementia risk. Ten years of prospective cohort data (2011-2020) were retrieved from the National Health and Aging Trends Study, a nationally representative sample of 5,362 U.S. older adults aged 65+. Cox regression analysed time to dementia diagnosis using nativity status (foreign- or native-born) and composite scores for neighbourhood physical disorder (litter, graffiti and vacancies) and social cohesion (know, help and trust each other), after applying sampling weights and imputing missing data. In a weighted sample representing 26.9 million older adults, about 9.5% (n = 2.5 million) identified as foreign-born and 24.4% (n = 6.5 million) had an incident dementia diagnosis. Average baseline neighbourhood physical disorder was 0.19 (range 0-9), and baseline social cohesion was 4.28 (range 0-6). Baseline neighbourhood physical disorder was significantly higher among foreign-born (mean = 0.28) compared to native-born (mean = 0.18) older adults (t = -2.4, p = .02). Baseline neighbourhood social cohesion was significantly lower for foreign-born (mean = 3.57) compared to native-born (mean = 4.33) older adults (t = 5.5, p < .001). After adjusting for sociodemographic, health and neighbourhood variables, foreign-born older adults had a 51% significantly higher dementia risk (adjusted hazard ratio = 1.51, 95% CI = 1.19-1.90, p < .01). There were no significant interactions for nativity with neighbourhood physical disorder or social cohesion. Our findings suggest that foreign-born older adults have higher neighbourhood physical disorder and lower social cohesion compared to native-born older adults. Despite the higher dementia risk, we observed for foreign-born older adults, and this relationship was not moderated by either neighbourhood physical disorder or social cohesion. Further research is needed to understand what factors are contributing to elevated dementia risk among foreign-born older adults.

Multimodal Machine Learning for 10-Year Dementia Risk Prediction: The Framingham Heart Study.

Early prediction of dementia risk is crucial for effective interventions. Given the known etiologic heterogeneity, machine learning methods leveraging multimodal data, such as clinical manifestations, neuroimaging biomarkers, and well-documented risk factors, could predict dementia more accurately than single modal data. This study aims to develop machine learning models that capitalize on neuropsychological (NP) tests, magnetic resonance imaging (MRI) measures, and clinical risk factors for 10-year dementia prediction. This study included participants from the Framingham Heart Study, and various data modalities such as NP tests, MRI measures, and demographic variables were collected. CatBoost was used with Optuna hyperparameter optimization to create prediction models for 10-year dementia risk using different combinations of data modalities. The contribution of each modality and feature for the prediction task was also quantified using Shapley values. This study included 1,031 participants with normal cognitive status at baseline (age 75±5 years, 55.3% women), of whom 205 were diagnosed with dementia during the 10-year follow-up. The model built on three modalities demonstrated the best dementia prediction performance (AUC 0.90±0.01) compared to single modality models (AUC range: 0.82-0.84). MRI measures contributed most to dementia prediction (mean absolute Shapley value: 3.19), suggesting the necessity of multimodal inputs. This study shows that a multimodal machine learning framework had a superior performance for 10-year dementia risk prediction. The model can be used to increase vigilance for cognitive deterioration and select high-risk individuals for early intervention and risk management.

Early detection of Dementia in Type 2 Diabetes population: Predictive analytics using Machine learning approach.

The possible association between diabetes mellitus and dementia has raised concerns, given the observed coincidental occurrences. This study aims to develop a personalized predictive model, utilizing artificial intelligence, to assess the 5-year and 10-year dementia risk among patients with Type 2 Diabetes Mellitus (T2DM) who are prescribed antidiabetic medications. This retrospective multicenter study used data from Taipei Medical University Clinical Research Database, which comprises electronic medical records from three hospitals in Taiwan. This study applied eight machine learning algorithms to develop prediction models, including logistic regression (LR), linear discriminant analysis (LDA), gradient boosting machine (GBM), lightGBM (LBGM), AdaBoost, random forest, extreme gradient boosting (XGBoost), and artificial neural network (ANN). These models incorporated a range of variables, encompassing patient characteristics, comorbidities, medication usage, laboratory results, and examination data. This study involved a cohort of 43,068 patients diagnosed with T2DM, which accounted for a total of 1,937,692 visits. For model development and validation, 1,300,829 visits were utilized, while an additional 636,863 visits were reserved for external testing. The area under the curve (AUC) of the prediction models range from 0.67 for the logistic regression to 0.98 for the artificial neural networks. Based on the external test results, the model built using the ANN algorithm has the best AUC: 0.97 (5-year follow-up period) and 0.98 (10-year follow-up period). Based on the best model (ANN), age, gender, triglyceride, HbA1c, anti-diabetic agents, stroke history, and other long-term medications were the most important predictors. We have successfully developed a novel computer-aided dementia risk prediction model that can facilitate the clinical diagnosis and management of patients prescribed with antidiabetic medications. However, further investigation is required to assess the model's feasibility and external validity.

Estimating Dementia Risk Using Multifactorial Prediction Models

The clinical value of current multifactorial algorithms for individualized assessment of dementia risk remains unclear. To evaluate the clinical value associated with 4 widely used dementia risk scores in estimating 10-year dementia risk. This prospective population-based UK Biobank cohort study assessed 4 dementia risk scores at baseline (2006-2010) and ascertained incident dementia during the following 10 years. Replication with a 20-year follow-up was based on the British Whitehall II study. For both analyses, participants who had no dementia at baseline, had complete data on at least 1 dementia risk score, and were linked to electronic health records from hospitalizations or mortality were included. Data analysis was conducted from July 5, 2022, to April 20, 2023. Four existing dementia risk scores: the Cardiovascular Risk Factors, Aging and Dementia (CAIDE)-Clinical score, the CAIDE-APOE-supplemented score, the Brief Dementia Screening Indicator (BDSI), and the Australian National University Alzheimer Disease Risk Index (ANU-ADRI). Dementia was ascertained from linked electronic health records. To evaluate how well each score predicted the 10-year risk of dementia, concordance (C) statistics, detection rate, false-positive rate, and the ratio of true to false positives were calculated for each risk score and for a model including age alone. Of 465 929 UK Biobank participants without dementia at baseline (mean [SD] age, 56.5 [8.1] years; range, 38-73 years; 252 778 [54.3%] female participants), 3421 were diagnosed with dementia at follow-up (7.5 per 10 000 person-years). If the threshold for a positive test result was calibrated to achieve a 5% false-positive rate, all 4 risk scores detected 9% to 16% of incident dementia and therefore missed 84% to 91% (failure rate). The corresponding failure rate was 84% for a model that included age only. For a positive test result calibrated to detect at least half of future incident dementia, the ratio of true to false positives ranged between 1 to 66 (for CAIDE-APOE-supplemented) and 1 to 116 (for ANU-ADRI). For age alone, the ratio was 1 to 43. The C statistic was 0.66 (95% CI, 0.65-0.67) for the CAIDE clinical version, 0.73 (95% CI, 0.72-0.73) for the CAIDE-APOE-supplemented, 0.68 (95% CI, 0.67-0.69) for BDSI, 0.59 (95% CI, 0.58-0.60) for ANU-ADRI, and 0.79 (95% CI, 0.79-0.80) for age alone. Similar C statistics were seen for 20-year dementia risk in the Whitehall II study cohort, which included 4865 participants (mean [SD] age, 54.9 [5.9] years; 1342 [27.6%] female participants). In a subgroup analysis of same-aged participants aged 65 (±1) years, discriminatory capacity of risk scores was low (C statistics between 0.52 and 0.60). In these cohort studies, individualized assessments of dementia risk using existing risk prediction scores had high error rates. These findings suggest that the scores were of limited value in targeting people for dementia prevention. Further research is needed to develop more accurate algorithms for estimation of dementia risk.

Editors' Note: Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline

Dr. Salinas and colleagues examined the association of loneliness at baseline with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of Alzheimer disease and related dementia (ADRD) vulnerability in 2,308 participants in the population-based Framingham study cohorts. They found that loneliness was associated with increased dementia risk, with the risk tripling in adults whose baseline risk would otherwise be fairly low on the basis of age and genetic risk and that loneliness was also associated with worse markers of ADRD vulnerability, implying a potential early pathogenetic role. In response, Dr. Daly notes that a similar association was seen between frailty and 10-year dementia risk. He suggests studying the relationship between longitudinal changes in loneliness and neuroanatomical or neuropathologic measures, and the relationship of loneliness to frailty. He also emphasizes the importance of taking action against loneliness in society, which was aggravated by the COVID-19 pandemic especially among lower socioeconomic strata, to mitigate further social disparities in dementia risk. Responding to these comments, Dr. Salinas notes that the study team has begun exploring longitudinal associations of loneliness with dementia-related measures in another cohort, and points to compelling findings of greater cortical amyloid and entorhinal tau accumulation in patients with loneliness in the Harvard Aging Brain Study. Dr. Salinas echoes the need for interventions targeting loneliness and social isolation. This correspondence underscores our growing understanding of the role that psychosocial determinants of health play in the development of dementia. Although it seems clear that a social brain fares better than a lonely one over time, the question remains as to whether the lonely brain can be “rescued” by social interventions. Dr. Salinas and colleagues examined the association of loneliness at baseline with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of Alzheimer disease and related dementia (ADRD) vulnerability in 2,308 participants in the population-based Framingham study cohorts. They found that loneliness was associated with increased dementia risk, with the risk tripling in adults whose baseline risk would otherwise be fairly low on the basis of age and genetic risk and that loneliness was also associated with worse markers of ADRD vulnerability, implying a potential early pathogenetic role. In response, Dr. Daly notes that a similar association was seen between frailty and 10-year dementia risk. He suggests studying the relationship between longitudinal changes in loneliness and neuroanatomical or neuropathologic measures, and the relationship of loneliness to frailty. He also emphasizes the importance of taking action against loneliness in society, which was aggravated by the COVID-19 pandemic especially among lower socioeconomic strata, to mitigate further social disparities in dementia risk. Responding to these comments, Dr. Salinas notes that the study team has begun exploring longitudinal associations of loneliness with dementia-related measures in another cohort, and points to compelling findings of greater cortical amyloid and entorhinal tau accumulation in patients with loneliness in the Harvard Aging Brain Study. Dr. Salinas echoes the need for interventions targeting loneliness and social isolation. This correspondence underscores our growing understanding of the role that psychosocial determinants of health play in the development of dementia. Although it seems clear that a social brain fares better than a lonely one over time, the question remains as to whether the lonely brain can be “rescued” by social interventions.

Reader Response: Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline.

There are striking parallels between the recent finding of Salinas and colleagues that older adults who described feeling lonely 3 or more days a week had a greater 10-year risk of developing dementia1 and the report by Wallace et al.2 of a strong 10-year link between frailty and increased dementia risk. In other words, research shows that individuals with dementia tend to have been lonely or frail in the decade before developing the condition.

Author Response: Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline.

We greatly appreciate the comment on our findings.1 It is true that the associations of loneliness and frailty with increased dementia risk raise important questions that merit further exploration. We have begun to explore this by examining these longitudinal associations in the HAALSI cohort, which is composed of predominantly Black older adults from rural South Africa.2 Although associations of loneliness are identified with notable neuroanatomical measures (lower total cerebral volume and greater white matter injury) in our present study, this was a cross-sectional analysis and would benefit from further validation. The temporal relationships of these pathways are worth exploring further, especially given prior cross-sectional evidence from the Harvard Aging Brain Study identifying associations between greater levels of loneliness and greater accumulation of cortical amyloid and right entorhinal tau on PET imaging.3,4 We agree that, in light of studies that continue to provide evidence that supports the relevance of these pathways, there needs to be further action against loneliness and social isolation through targeted interventions that address the psychosocial determinants of brain health.

Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life: The Framingham Heart Study.

The association between vascular risk factors and dementia varies with age, making generalizability of dementia risk prediction rules to individuals of different ages challenging. We determined the most important vascular risk factors for inclusion in age-specific dementia risk scores. Framingham Heart Study Original and Offspring cohort participants with available data on the Framingham Stroke Risk Profile (FSRP) at midlife (age 55; n = 4,899, 57% women), late life (ages 65 or 70), or later life (ages 75 or 80 [n = 2,386, 62% women]) were followed for 10-year incident dementia risk from ages 65, 70, 75, and 80. Age- and sex-adjusted midlife risk factors associated with 10-year risk of dementia from age 65 included FSRP (hazard ratio [HR] 1.16, 95% CI 1.06-1.26, per 1 SD increment in log-transformed score), diabetes mellitus (DM; HR 4.31, 95% CI 1.97-9.43), and systolic blood pressure (SBP; HR 1.12, 95% CI 1.02-1.24, per 10 mm Hg increment). Late-life risk factors associated with 10-year incident dementia from ages 65 or 70 included FSRP (age 65 only: HR 1.06, 95% CI 1.02-1.10), antihypertensive use (age 65 reported: HR 1.66, 95% CI 1.12-2.46), DM (age 65 reported: HR 1.96, 95% CI 1.09-3.52), atrial fibrillation (age 65 reported: HR 2.30, 95% CI 1.00-5.27), nonstroke cardiovascular disease (nsCVD; age 65 reported: HR 1.95, 95% CI 1.24-3.07), and stroke (age 70 only: HR 3.61, 95% CI 2.21-5.92). Later-life risk factors associated with 10-year incident dementia from ages 75 or 80 included antihypertensive use (age 80 only: HR 0.74, 95% CI 0.62-0.89), DM (age 80 reported: HR 1.40, 95% CI 1.04-1.89), atrial fibrillation (age 80 reported: HR 1.43, 95% CI 1.07-1.92), and stroke (age 80 reported: HR 1.63, 95% CI 1.13-2.35). In stepwise models, SBP and DM at age 55, nsCVD at age 65, DM and stroke at ages 70 and 75, and DM, stroke, and use of antihypertensives (protective) at age 80 were the most important vascular risk factors for dementia. Our findings support the use of age-specific dementia risk scores, which should prioritize including, at age 55, SBP and DM; at age 65, nsCVD; at ages 70 and 75, DM and stroke; and at age 80, DM, stroke, and antihypertensive use.

Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline.

Background and ObjectivesLoneliness is common, and its prevalence is rising. The relationship of loneliness with subsequent dementia and the early preclinical course of Alzheimer disease and related dementia (ADRD) remains unclear. Thus, the primary objective of this study was to determine the association of loneliness with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of ADRD vulnerability.MethodsThis was a retrospective analysis of prospectively collected data from the population-based Framingham Study cohorts (September 9, 1948–December 31, 2018). Eligible participants had loneliness assessed and were dementia-free at baseline. Loneliness was recorded with the Center for Epidemiologic Studies Depression Scale, defined conservatively as feeling lonely ≥3 days in the past week. The main outcomes were incident dementia over a 10-year period, cognition, and MRI brain volumes and white matter injury.ResultsOf 2,308 participants (mean age 73 [SD 9] years, 56% women) who met eligibility in the dementia sample, 14% (329 of 2,308) developed dementia and 6% (144 of 2,308) were lonely. Lonely (versus not lonely) adults had higher 10-year dementia risk (age-, sex-, and education-adjusted hazard ratio 1.54, 95% CI 1.06–2.24). Lonely participants <80 years of age without APOE ε4 alleles had a 3-fold greater risk (adjusted hazard ratio 3.03, 95% CI, 1.63–5.62). Among 1,875 persons without dementia who met eligibility in the cognition sample (mean age 62 [SD 9] years, 54% women), loneliness associated with poorer executive function, lower total cerebral volume, and greater white matter injury.DiscussionOver 10 years of close clinical dementia surveillance in this cohort study, loneliness was associated with increased dementia risk; this tripled in adults whose baseline risk would otherwise be relatively low on the basis of age and genetic risk, representing a majority of the US population. Loneliness was also associated with worse neurocognitive markers of ADRD vulnerability, suggesting an early pathogenic role. These findings may have important clinical and public health implications given observed loneliness trends.Classification of EvidenceThis study provides Class I evidence that loneliness increases the 10-year risk of developing dementia.

Herpes Labialis, Chlamydophila pneumoniae, Helicobacter pylori, and Cytomegalovirus Infections and Risk of Dementia: The Framingham Heart Study.

An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are. Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C.pneumoniae), Helicobacter pylori (H. pylori), and cytomegalovirus (CMV) modifies the risk of dementia in a populational cohort. Questionnaires regarding incidence of herpes infections were administered to Original Framingham Study participants (n = 2,632). Serologies for C. pneumoniae, H. pylori, and CMV were obtained in Original (n = 2,351) and Offspring cohort (n = 3,687) participants. Participants are under continuous dementia surveillance. Brain MRI and neuropsychological batteries were administered to Offspring participants from 1999-2005. The association between each infection and incident dementia was tested with Cox models. Linear models were used to investigate associations between MRI or neuropsychological parameters and serologies. There was no association between infection serologies and dementia incidence, total brain volume, and white matter hyperintensities. Herpes labialis was associated with reduced 10-year dementia risk (HR 0.66, CI 0.46-0.97), but not for the duration of follow-up. H. pylori antibodies were associated with worse global cognition (β -0.14, CI -0.22, -0.05). We found no association between measures of chronic infection and incident dementia, except for a reduction in 10-year dementia risk for patients with herpes labialis. This unexpected result requires confirmation and further characterization, concerning antiviral treatment effects and capture of episodes.

The type 2 diabetes-specific dementia risk score (DSDRS) is associated with frailty, cognitive and functional status amongst Mexican community-dwelling older adults

BackgroundThe type 2 diabetes (T2D) specific dementia-risk score (DSDRS) was developed to evaluate dementia risk in older adults with T2D. T2D-related factors have been shown increase the risk of age-related conditions, which might also increase dementia risk. Here, we investigate the associations of DSDRS with frailty, disability, quality of life (QoL) and cognition in community-dwelling older adults with T2D.MethodsWe included 257 community-dwelling older adults with T2D to evaluate the association between DSDRS and Mini-mental state examination (MMSE), Isaac’s set-test (IST), clock drawing test (CDT), quality of life (SF-36), risk of malnutrition (Mini-Nutritional Assessment or MNA), as well as frailty, Katz’ and Lawton-Brody scores. We also assessed the phenotype and correlates of high-estimated dementia risk by assessing individuals with DSDRS >75th age-specific percentiles.ResultsMean age of participants was 78.0 ± 6.2 years. DSDRS showed a significant correlation with MMSE test, IST, CDT, SF-36, MNA, Lawton-Brody and Katz scores, and an increasing number of frailty components. DSDRS was higher among frail, pre-frail, and subjects with limited ADL and IADL (p < 0.001). Participants with DSDRS >75th age-specific percentiles had lower education, MMSE, IST, SF-36, MNA, Katz, Lawton-Brody, and higher frailty scores. High-estimated 10-year dementia risk was associated with ADL and IADL disability, frailty and risk of malnutrition. When assessing individual components of DSDRS, T2D-related microvascular complications were associated to all outcome measures.ConclusionThe DSDRS is associated with frailty, disability, malnutrition and lower cognitive performance. These findings support that T2D-related factors have significant burden on functional status, QoL, disability and dementia risk.

Development and Validation of a Dementia Risk Prediction Model in the General Population: An Analysis of Three Longitudinal Studies.

Identification of individuals at high risk of dementia is essential for development of prevention strategies, but reliable tools are lacking for risk stratification in the population. The authors developed and validated a prediction model to calculate the 10-year absolute risk of developing dementia in an aging population. In a large, prospective population-based cohort, data were collected on demographic, clinical, neuropsychological, genetic, and neuroimaging parameters from 2,710 nondemented individuals age 60 or older, examined between 1995 and 2011. A basic and an extended model were derived to predict 10-year risk of dementia while taking into account competing risks from death due to other causes. Model performance was assessed using optimism-corrected C-statistics and calibration plots, and the models were externally validated in the Dutch population-based Epidemiological Prevention Study of Zoetermeer and in the Alzheimer's Disease Neuroimaging Initiative cohort 1 (ADNI-1). During a follow-up of 20,324 person-years, 181 participants developed dementia. A basic dementia risk model using age, history of stroke, subjective memory decline, and need for assistance with finances or medication yielded a C-statistic of 0.78 (95% CI=0.75, 0.81). Subsequently, an extended model incorporating the basic model and additional cognitive, genetic, and imaging predictors yielded a C-statistic of 0.86 (95% CI=0.83, 0.88). The models performed well in external validation cohorts from Europe and the United States. In community-dwelling individuals, 10-year dementia risk can be accurately predicted by combining information on readily available predictors in the primary care setting. Dementia prediction can be further improved by using data on cognitive performance, genotyping, and brain imaging. These models can be used to identify individuals at high risk of dementia in the population and are able to inform trial design.

Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study.

Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (APOE) genotype. We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and blood sampling at baseline. Diagnoses of dementia and cerebrovascular disease were obtained from the Danish National Patient Registry up to Nov. 10, 2014. Among 104 537 individuals, the absolute 10-year risk of Alzheimer disease in 3017 women and men who were carriers of the APOE ɛ44 genotype was, respectively, 7% and 6% at age 60-69 years, 16% and 12% at age 70-79 years, and 24% and 19% at age 80 years and older. Corresponding values for all dementia were 10% and 8%, 22% and 19%, and 38% and 33%, respectively. Adjusted hazard ratios (HRs) for all dementia increased by genotype, from genotype ɛ22 to ɛ32 to ɛ33 to ɛ42 to ɛ43 to ɛ44 (p for trend < 0.001). Compared with ɛ33 carriers, ɛ44 carriers were more likely to develop Alzheimer disease (adjusted HR 8.74, 95% confidence interval [CI] 7.08-10.79), vascular dementia (adjusted HR 2.87, 95% CI 1.54-5.33), unspecified dementia (adjusted HR 4.68, 95% CI 3.74-5.85) and all dementia (adjusted HR 5.77, 95% CI 4.89-6.81). Age, sex and APOE genotype robustly identify high-risk groups for Alzheimer disease and all dementia. These groups can potentially be targeted for preventive interventions.

The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.

ObjectivesElectronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.Methods and findingsA cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer’s disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer’s disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20–1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24–12.75), falls (cOR = 2.36;95%CI:2.31–2.41), depression (cOR = 2.03; 95%CI:1.98–2.09) or anxiety (cOR = 1.27; 95%CI:1.23–1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54–1.58).ConclusionsMost people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.

External validation of four dementia prediction models for use in the general community-dwelling population: a comparative analysis from the Rotterdam Study

To systematically review the literature for dementia prediction models for use in the general population and externally validate their performance in a head-to-head comparison. We selected four prediction models for validation: CAIDE, BDSI, ANU-ADRI and DRS. From the Rotterdam Study, 6667 non-demented individuals aged 55 years and older were assessed between 1997 and 2001. Subsequently, participants were followed for dementia until 1 January, 2015. For each individual, we computed the risk of dementia using the reported scores from each prediction model. We used the C-statistic and calibration plots to assess the performance of each model to predict 10-year risk of all-cause dementia. For comparisons, we also evaluated discriminative accuracy using only the age component of these risk scores for each model separately. During 75,581 person-years of follow-up, 867 participants developed dementia. C-statistics for 10-year dementia risk prediction were 0.55 (95% CI 0.53–0.58) for CAIDE, 0.78 (0.76–0.81) for BDSI, 0.75 (0.74–0.77) for ANU-ADRI, and 0.81 (0.78–0.83) for DRS. Calibration plots showed that predicted risks were too extreme with underestimation at low risk and overestimation at high risk. Importantly, in all models age alone already showed nearly identical discriminative accuracy as the full model (C-statistics: 0.55 (0.53–0.58) for CAIDE, 0.81 (0.78–0.83) for BDSI, 0.77 (0.75–0.79) for ANU-ADRI, and 0.81 (0.78–0.83) for DRS). In this study, we found high variability in discriminative ability for predicting dementia in an elderly, community-dwelling population. All models showed similar discriminative ability when compared to prediction based on age alone. These findings highlight the urgent need for updated or new models to predict dementia risk in the general population.

A Study on Clinical Determinants and one year Follow-Up of Dementia and Mild Cognitive Impairment Following Ischemic Stroke

Cognitive impairment due to cerebrovascular disease is termed “Vascular Cognitive Impairment” and forms a spectrum that includes Vascular Dementia and milder forms of cognitive impairment referred to as Vascular Mild Cognitive Impairment. While Vascular Dementia is the second most common cause of dementia, the milder form Vascular Mild Cognitive Impairment is much more common. Nearly half of individuals with Vascular Mild Cognitive Impairment convert to dementia after five years. Vascular cognitive disorders are poised to become the silent epidemic of the 21st century and contribute significantly to mortality, disability, and decreased quality of life. It is now clear that Vascular Cognitive Impairment is not a single entity, but represents a complex neurological disorder that occurs as a result of interaction between vascular risk factors and brain parenchymal changes such as macro and micro infarcts, haemorrhages, white matter changes, and brain atrophy occurring in an ageing brain. Factors that determine progression of milder form Vascular Mild Cognitive Impairment to dementia are not well understood. Since Vascular Cognitive Impairment is amenable to prevention and treatment, there is a pressing need to identify factors that protect or predispose to it. Dementia is a common sequelae of stroke with a frequency ranging from 16% to 32%. In a more recent epidemiological study, the 10- year risk of dementia after stroke was estimated at 19.3%, compared to 11.0% in non-stroke controls. This twofold increase in dementia following stroke is in contrast with a nine fold increase reported in some previous studies. The large variation in rates is accounted for by variations in the populations studied as well as the criteria used for the diagnosis of dementia. As the definition of vascular dementia is currently being refined, it is timely that these studies be revisited. One aspect of this reassessment is the consideration of vascular mild cognitive impairment in stroke patients, which has thus far received little attention. 1. This study supports the high prevalence of dementia and mild cognitive impairment following stroke, especially in older individuals, and highlights the importance of cognitive reserve. 2. The contribution of cerebrovascular risk factors is not independent of the stroke risk. 3. Subcortical dementia was the most frequent subtype of Vascular Dementia in our hospital-based series. 4. Stroke volume is a significant determinant of post-stroke dementia. 5. This study suggests that cognitive performance in stroke patients may change over time. It also suggests that progression of cognitive impairment is common after stroke. 6. The cognitive impairment is not only frequent with stroke, but also significantly affects functional adaptation after the acute phase. Efforts to modify the course of acute stroke should also take into account chronic brain failure as an outcome.

Dementia and Alzheimer's Disease among Older Kidney Transplant Recipients.

Older patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked to Medicare claims through the US Renal Data System. We estimated dementia and AD risk (cumulative incidence) and studied factors associated with these sequelae using competing risks models. We estimated the risk of death-censored graft loss and mortality after developing dementia or the AD subtype of dementia, separately, using adjusted Cox proportional hazards models. Older recipients had a 10-year dementia risk ranging from 5.1% for recipients aged 55-60 years to 17.0% for recipients aged ≥75 years; 10-year AD risk ranged from 1.0% to 6.7%, respectively. The strongest predictors for dementia and AD were older recipient age and pretransplant diabetes. The 10-year graft loss risk was 28.8% for those who did not develop dementia and 43.1% for those who did, and the corresponding mortality risks were 55.7% and 89.9%, respectively. Older recipients with dementia had a 1.52-fold (95% confidence interval, 1.39 to 1.68) increased risk of graft loss and a 2.38-fold (95% confidence interval, 2.26 to 2.49) increased risk of mortality. We observed similar results for AD. We conclude that older KT recipients have a high risk of post-KT dementia and AD, and these sequelae associate with a profound effect on patient and graft survival.

Dietary B Vitamins and a 10-Year Risk of Dementia in Older Persons.

B vitamins may lower the risk of dementia, yet epidemiological findings, mostly from countries with folic acid fortification, have remained inconsistent. We evaluated in a large French cohort of older persons the associations between dietary B vitamins and long-term incident dementia. We included 1321 participants from the Three-City Study who completed a 24 h dietary recall, were free of dementia at the time of diet assessment, and were followed for an average of 7.4 years. In Cox proportional hazards models adjusted for multiple potential confounders, including overall diet quality, higher intake of folate was inversely associated with the risk of dementia (p for trend = 0.02), with an approximately 50% lower risk for individuals in the highest compared to the lowest quintile of folate (HR = 0.47; 95% CI 0.28; 0.81). No association was found for vitamins B6 and B12. In conclusion, in a large French cohort with a relatively low baseline folate status (average intake = 278 µg/day), higher folate intakes were associated with a decreased risk of dementia.