Search

White matter hyperintensities are common radiological findings in ageing and a typical manifestation of cerebral small vessel disease. White matter hyperintensity burden is evaluated by quantifying their volume; however, subtle changes in the white matter may not be captured by white matter hyperintensity volumetry. In this cross-sectional study, we investigated whether magnetic resonance imaging texture of both white matter hyperintensities and normal appearing white matter was associated with reaction time, white matter hyperintensity volume and dementia risk in a midlife cognitively normal population. Data from 183 cognitively healthy midlife adults from the PREVENT-Dementia study (mean age 51.9 ± 5.4; 70% females) were analysed. White matter hyperintensities were segmented from 3 Tesla fluid-attenuated inversion recovery scans using a semi-automated approach. The fluid-attenuated inversion recovery images were bias field corrected and textural features (intensity mean and standard deviation, contrast, energy, entropy, homogeneity) were calculated in white matter hyperintensities and normal appearing white matter based on generated textural maps. Textural features were analysed for associations with white matter hyperintensity volume, reaction time and the Cardiovascular Risk Factors, Aging and Dementia risk score using linear regression models adjusting for age and sex. The extent of normal appearing white matter surrounding white matter hyperintensities demonstrating similar textural associations to white matter hyperintensities was further investigated by defining layers surrounding white matter hyperintensities at increments of 0.86 mm thickness. Lower mean intensity within white matter hyperintensities was a significant predictor of longer reaction time (t = −3.77, P

Additional file 2: Appendix 2. Full list of most Important themes (Diagnosis group).

Additional file 1: Appendix 1. Full list of most Frequent themes (Diagnosis group).

Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration.Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration.Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage.Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

An expanding body of research highlights that a cognitively engaged lifestyle may protect against neurodegeneration in late life (e.g., thereby promoting cognitive reserve). The majority of research in this area uses education as a proxy to investigate the cognitive reserve hypothesis; however, more recent findings suggest that other factors from the lifespan contribute to cognitive reserve. The current study examined whether access to cognitive resources in childhood (e.g., number of books at home) influenced healthy and impaired life expectancies using coordinated analyses of data from eight countries. Multistate survival models examined transitions between healthy, mild, and severely impaired cognitive states and death, which were used to compute life expectancies for individuals with and without impairment. Controlling for age, sex, education, SES, and country, analyses revealed a pattern consistent with the cognitive reserve hypothesis. Specifically, having access to more cognitive resources in childhood was associated with compression of morbidity—longer life expectancy free of impairment and less time spent with cognitive impairment. Cross-country differences in this effect will be discussed. Overall, these findings underscore the importance of childhood cognitive stimulation for cognitive health in later life and emphasize the need for a lifespan-focused approach to studying cognitive reserve.

$\textbf{Background}$ vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. $\textbf{Objective}$ to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Risk of 2-year incident dementia in individuals with disease and cognitive impairment was also tested. $\textbf{Methods}$ participants were from the Cognitive Function and Ageing Study. At baseline, 13,004 individuals aged ≥65 years were enrolled into the study. Individuals were grouped by baseline disorder status (present, absent) for each condition. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). Dementia was assessed at 2 years. $\textbf{Results}$ in the cross-sectional analysis, hypertension, PVD and CHD were not associated with cognitive impairment. Stroke was associated with impaired global (MMSE) and CAMCOG sub-scale (including memory and non-memory) scores. Diabetes was associated with impairments in global cognitive function (MMSE) and abstract thinking. In the longitudinal analysis, cognitive impairments were associated with incident dementia in all groups. $\textbf{Conclusion}$ the neuropsychological profile in individuals with vascular disorders depends on the specific condition investigated. In all conditions cognitive impairment is a risk factor for dementia. A better understanding of which cognitive domains are affected in different disease groups could help improve operationalisation of the neuropsychological criteria for VCI-ND and could also aid with the development of dementia risk prediction models in persons with vascular disease.

Objective: To forecast dementia prevalence with a dynamic modelling approach that integrates calendar trends in dementia incidence with those for mortality and cardiovascular disease.Design: Modelling study.Setting: General adult population of England and Wales.Participants: The English Longitudinal Study of Ageing (ELSA) is a representative panel study with six waves of data across 2002-13. Men and women aged 50 or more years, selected randomly, and their cohabiting partners were recruited to the first wave of ELSA (2002-03). 11392 adults participated (response rate 67%). To maintain representativeness, refreshment participants were recruited to the study at subsequent waves. The total analytical sample constituted 17 906 people. Constant objective criteria based on cognitive and functional impairment were used to ascertain dementia cases at each wave.Main outcome measures: To estimate calendar trends in dementia incidence, correcting for bias due to loss to follow-up of study participants, a joint model of longitudinal and time-to-event data was fitted to ELSA data. To forecast future dementia prevalence, the probabilistic Markov model IMPACT-BAM (IMPACT-Better Ageing Model) was developed. IMPACT-BAM models transitions of the population aged 35 or more years through states of cardiovascular disease, cognitive and functional impairment, and dementia, to death. It enables prediction of dementia prevalence while accounting for the growing pool of susceptible people as a result of increased life expectancy and the competing effects due to changes in mortality, and incidence of cardiovascular disease.Results: In ELSA, dementia incidence was estimated at 14.3 per 1000 person years in men and 17.0/1000 person years in women aged 50 or more in 2010. Dementia incidence declined at a relative rate of 2.7% (95% confidence interval 2.4% to 2.9%) for each year during 2002-13. Using IMPACT-BAM, we estimated there were approximately 767 000 (95% uncertainty interval 735 000 to 797 000) people with dementia in England and Wales in 2016. Despite the decrease in incidence and age specific prevalence, the number of people with dementia is projected to increase to 872 000, 1 092 000, and 1 205 000 in 2020, 2030, and 2040, respectively. A sensitivity analysis without the incidence decline gave a much larger projected growth, of more than 1.9 million people with dementia in 2040.Conclusions: Age specific dementia incidence is declining. The number of people with dementia in England and Wales is likely to increase by 57% from 2016 to 2040. This increase is mainly driven by improved life expectancy.

This study explores the association between cognitive ability in childhood and midlife and bone health outcomes in early old age; and the relationships of these bone measures with contemporaneous and subsequent cognitive ability in the MRC National Survey of Health and Development (NSHD). This British birth cohort assessed areal and volumetric bone mineral density (aBMD and vBMD) at age 60-64, derived from peripheral quantitative computed tomography and dual-energy X-ray absorptiometry, and cognitive performance from childhood to age 69, among 866 women and 792 men. Cognitive performance at age 15 was assessed using tests of verbal and non-verbal ability, and mathematics; and memory and search speed tasks were administered at ages 53, 60-64, and 69. Covariates included body size, pubertal timing, smoking, leisure time physical activity, socioeconomic circumstances and menopause timing. Multiple linear regression analyses showed that higher childhood cognitive ability was associated with higher hip aBMD, in women, and greater cortical and trabecular vBMD, in men. For women, there were positive associations between hip aBMD and total vBMD, and contemporaneous cognitive ability with associations also extending to subsequent cognitive ability for total vBMD. For men, some associations with trabecular and total vBMD emerged at ages 60-64 and 69 but only after adjusting for education, occupational class and health behaviors. Our findings highlight that higher cognitive ability in childhood is associated with BMD in early old age and these associations might be explained by social and behavioral pathways. The results suggest that individuals with greater cognitive ability in early life are more likely to engage in healthy behaviors (e.g., leisure time physical activity) in adulthood, which in turn are associated with greater BMD later in life. Associations between bone health and cognitive performance should be considered within a life course framework; and the potential role of smoking and physical activity should be addressed when advising adults at high future risk of osteoporosis and fracture.

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE points per year (95% CI, -0.57 to -0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional -0.16 MMSE points per year (95% CI, -0.29 to -0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level-matched controls. Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia.

Importance Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated.\ud \ud Objective To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia.\ud \ud Design, Setting, and Participants Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors.\ud \ud Exposures Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed.\ud \ud Outcomes Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death.\ud \ud Results There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (−2.8 points; 95% CI, −4.5 to −1.0; P

Objectives (1) To describe changes in objective measures of physical capability between ages 53 and 60–64 years; (2) to investigate the associations of behavioural risk factors (obesity, physical inactivity, smoking) and number of health conditions (range 0–4: hand osteoarthritis (OA); knee OA; severe respiratory symptoms; other disabling or life-threatening conditions (ie, cancer, cardiovascular disease, diabetes)) at age 53 years with these changes. Design Nationally representative prospective birth cohort study. Setting England, Scotland and Wales. Participants Up to 2093 men and women from the Medical Research Council National Survey of Health and Development, who have been followed-up since birth in 1946, and underwent physical capability assessments performed by nurses following standard protocols in 1999 and 2006–2010. Main outcome measures Grip strength and chair rise speed were assessed at ages 53 and 60–64 years. Four categories of change in grip strength and chair rise speed were identified: decline, stable high, stable low, a reference group who maintained physical capability within a ‘normal’ range. Results Less healthy behavioural risk scores and an increase in the number of health conditions experienced were associated in a stepwise fashion with increased risk of decline in physical capability, and also of having low levels at baseline and remaining low. For example, the sex and mutually adjusted relative-risk ratios (95% CI) of being in the stable low versus reference category of chair rise speed were 1.58 (1.35–1.86) and 1.97 (1.57–2.47) per 1 unit change in behavioural risk score and health indicator count, respectively. Conclusions These findings provide evidence of the associations of a range of modifiable factors with age-related changes in physical capability. They suggest the need to target multiple risk factors at least as early as mid-life when aiming to promote maintenance and prevent decline in physical capability in later life