Interventions Based on Behavior Change Techniques to Encourage Physical Activity or Decrease Sedentary Behavior in Community-Dwelling Adults Aged 50-70: Systematic Review With Intervention Component Analysis.

Increasing physical activity (PA) and/or decreasing sedentary behaviors is important in the delay and prevention of long-term conditions. PA can help maintain function and independence and decrease the need for hospitalization/institutionalization. Activity rates often decline in later life resulting in a need for interventions that encourage uptake and adherence through the use of Behavior Change Techniques (BCTs). We conducted a systematic review of the evidence for interventions that included BCTs in community-dwelling adults with a mean age of 50-70. The review followed PRISMA guidelines. The interventions were psychosocial, nonpharmacological, and noninvasive interventions utilizing components based on BCTs that evaluated change in PA and/or sedentary behavior. Intervention Component Analysis (ICA) was used to synthesize effectiveness of intervention components. Twelve randomized controlled trials were included in this review. The mean sample age was 50-64. Thirteen BCTs were used across all studies, and the most commonly used techniques were goals and planning, feedback and monitoring, and natural consequences. Seven intervention components linked with BCTs were found: personalized goal setting, tailored feedback from facilitators, on-site and postintervention support, education materials and resources, reinforcing change on behavior and attitudes, self-reported monitoring, and social connectedness. All components, except for social connectedness, were associated with improved health behavior and PA levels. The interventions that use BCTs have incorporated strategies that reinforce change in behavior and attitudes toward PA.

Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78-94.

Amyloid-beta (Aß) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to 18F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aß. Good correspondence existed between binary (+/-) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8-17% of individuals being unstageable, i.e., not following the sequential progression of Aß deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aß, thus, it remains an open topic what constitutes abnormal brain Aß in the oldest-old and what is the best method to determine that.

Trajectories of self-reported hearing and their associations with cognition: evidence from the United Kingdom and United States of America.

OBJECTIVE: This study aimed to investigate the relationships between trajectories of change in self-reported hearing over eight years with subsequent effects on cognition, measured using episodic memory. METHODS: Data were drawn from 5 waves (2008-2016) of the English Longitudinal Study of England (ELSA) and the Health and Retirement Study (HRS), involving 4,875 individuals aged 50+ at the baseline in ELSA and 6,365 in HRS. The latent growth curve modelling was used to identify trajectories of hearing over eight years, and linear regression models were performed to investigate the relationship between hearing trajectory memberships and episodic memory scores, controlling for confounding factors. RESULTS: Five trajectories of hearing (stable very good, stable fair, poor to fair/good, good to fair, and very good to good) were retained in each study. Individuals whose hearing remains suboptimal and those whose hearing deteriorates within suboptimal levels throughout eight years have significantly poorer episodic memory scores at follow-up than those with stable very good hearing. Conversely, individuals whose hearing declines but is within an optimal category at baseline do not see significantly poorer episodic memory scores than those with consistently optimal hearing. There was no significant relationship between individuals whose hearing improved from suboptimal baseline levels to optimal by follow-up and memory in ELSA. However, analysis using HRS data shows a significant improvement for this trajectory group (-1.260, P < 0.001). CONCLUSIONS: Either stable fair or deterioration in hearing is associated with worse cognitive function, both stable good or improving hearing is associated with better cognitive function specifically episodic memory.

A prospective analysis examining frailty remission and the association with future falls risk in older adults in England.

BACKGROUND: Previous research has shown older adults experience dynamic changes in frailty status. This study aimed to determine the occurrence of sustained frailty remission and how remission is associated with falls risk. METHODS: Participants who contributed data to the analysis were in the English Longitudinal Study of Ageing from Waves 1 to 8 (2002-2017). Frailty was defined across waves using the frailty index and categorised into robust, pre-frail and frail. We classified participants who improved their frailty category from Wave 1 (2002) to Wave 2 (2004) and sustained/improved category again into Wave 3 (2006) and compared them with those who were either robust or frail across Waves 1-3. Cox proportional hazard modelling was used to determine the risk of incident falls reported at Waves 4-8, with results expressed as hazard ratios and 95% confidence intervals. RESULTS: Of 2,564 participants, 389 (15·2%) improved frailty category and sustained this during Waves 2-3, 1,489 (58·1%) remained robust and 686 (26·8%) remained frail during Waves 1-3. During the 10-year period (Waves 4-8), a total of 549 participants reported a fall. Compared with those who remained frail during Waves 1-3, those who with sustained frailty remission had a lower risk of future falls (HR 0·41; 95% CI = 0·36-0·45). CONCLUSIONS: Frailty remission is possible and can be sustained across 5 years. There is a lower risk of future falls in those who sustain frailty remission compared with those who remain frail.

Household wealth, neighbourhood deprivation and frailty amongst middle-aged and older adults in England: a longitudinal analysis over 15 years (2002-2017).

BACKGROUND: frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. OBJECTIVE: to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. DESIGN: population-based cohort study. SETTING: communities in England. SUBJECTS: in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. METHODS: multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. RESULTS: the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0-34.6%] and 11.7 (11.1-12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2-1.3) and 2.2 (95% CI = 2.1-2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. CONCLUSIONS: in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours.

Mid to late-life scores of depression in the cognitively healthy are associated with cognitive status and Alzheimer's disease pathology at death.

OBJECTIVES: Early diagnosis of Alzheimer's disease (AD) is essential for early interventions. Symptoms of depression could represent a prodromal stage of AD. Very early mood alterations may help to stratify those at highest risk of late-life AD. We aim to investigate associations between baseline/longitudinal scores for depression, presence of cognitive impairment and/or AD pathology at death. METHODS/DESIGN: Between 1991 and 2015, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent 10 waves of assessment using the Geriatric Depression Scale (GDS). AD pathology at death was evaluated in 106 eligible cases. Analyses aimed to examine associations between GDS scores, cognitive status and AD pathology (as measured by Braak stage, Thal phase and CERAD). RESULTS: Baseline GDS scores were significantly higher for those cognitively impaired at death than those cognitively normal. Significantly higher baseline GDS scores were found for those with greater Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores than those with lower CERAD scores. Similarly, significantly higher baseline GDS scores were found for those with a greater Braak stage than those with lower tau burden. These correlations remained after controlling for age at death, education and APOE ε4, but were less robust. Mean longitudinal GDS scores associated with cognition but not pathology. CONCLUSIONS: GDS scores collected approximately 20 years before death were associated with cognitive status and AD pathology at death. We postulate that early AD-related pathological change produces raised GDS scores due to an overlapping neural basis with depression, and that this may be considered as an early diagnostic marker for AD.

Healthcare system performance and socioeconomic inequalities in hearing and visual impairments in 17 European countries.

BACKGROUND: Socioeconomic status is associated with health status among older adults, including hearing and vision impairments, and healthcare system performance is an important consideration in examining that association. We explored the link between a country's healthcare system performance and the hearing and visual impairments of its people in Europe. METHODS: This study enrolled 65 332 individuals aged 50+ from 17 countries participating in the Survey of Health, Ageing and Retirement in Europe Wave 6. We used latent class analysis to identify groups of countries based on six domains of healthcare system performance. We then performed multiple logistic regressions to quantify the association between socioeconomic status and hearing and visual impairments adjusted for demographic and other co-variates; finally, we compared the patterns of observed associations in each of the country groups. RESULTS: The latent class analysis separated countries into three groups based on the performance of their healthcare systems: poor, moderate and high. Respondents in countries with moderate and poor healthcare performance were more likely to experience hearing and visual impairment than those in countries with high healthcare performance. With respect to hearing and visual impairments, wealth gradients at the individual level varied among countries in different healthcare performance groups, with less wealth associated with worse hearing and seeing only in the countries with moderate and poor healthcare performance. CONCLUSION: The relationships between wealth and hearing and visual impairments differ among countries with different healthcare performance.

Longitudinal sleep efficiency in the elderly and its association with health.

The relationships between older age and sleep efficiency have traditionally been assessed using cross-sectional studies that ignore changes within individuals as they age. This research examines the determinants of sleep efficiency, the heterogeneity in an individual's sleep efficiency trajectory across a period of up to 27 years in later life and its associations with health. The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort (n = 6,375; age 42-94 years) was used in this study. Depression and health data were collected using self-report validated instruments (Cornell Medical Index, Beck Depression Inventory and Geriatric Depression Scale). Longitudinal sleep and sociodemographic data were collected using a study-specific self-report questionnaire. A mixed-effect model was performed for sleep efficiency with adjustments for time-invariant and time-variant predictors. Latent class analysis was used to demonstrate subgroups of sleep efficiency trajectories and associations between sleep efficiency clusters and health history of the participants were investigated. Older adults have decreased sleep efficiency over time, with 18.6% decline between 40 and 100 years of age. Three sleep efficiency trajectory clusters were identified: high (32%), medium (50%) and low sleep efficiency (18%). Belonging to the high sleep efficiency cluster was associated with having lower prevalence of hypertension, circulatory problems, general arthritis, breathing problems and recurrent episodes of depression compared to the low efficiency cluster. Overall, ageing decreases sleep efficiency. However, there are detectable subgroups of sleep efficiency that are related to prevalence of different diseases.

Normative Estimates and Agreement Between 2 Measures of Health-Related Quality of Life in Older People With Frailty: Findings From the Community Ageing Research 75+ Cohort.

BACKGROUND: Previous studies have summarized evidence on health-related quality of life for older people, identifying a range of measures that have been validated, but have not sought to present results by degree of frailty. Furthermore, previous studies did not typically use quality-of-life measures that generate an overall health utility score. Health utility scores are a necessary component of quality-adjusted life-year calculations used to estimate the cost-effectiveness of interventions. METHODS: We calculated normative estimates in mean and standard deviation for EQ-5D-5L, short-form 36-item health questionnaire in frailty (SF-36), and short-form 6-dimension (SF-6D) for a range of established frailty models. We compared response distributions across dimensions of the measures and investigated agreement using Bland-Altman and interclass correlation techniques. RESULTS: The EQ-5D-5L, SF-36, and SF-6D scores decrease and their variability increases with advancing frailty. There is strong agreement between the EQ-5D-5L and SF-6D across the spectrum of frailty. Agreement is lower for people who are most frail, indicating that different components of the 2 instruments may have greater relevance for people with advancing frailty in later life. There is a greater risk of ceiling effects using the EQ-5D-5L rather than the SF-6D. CONCLUSIONS: We recommend the SF-36/SF-6D as an appropriate measure of health-related quality of life for clinical trials if fit older people are the planned target. In trials of interventions involving older people with increasing frailty, we recommend that both the EQ-5D-5L and SF36/SF6D are included, and are used in sensitivity analyses as part of cost-effectiveness evaluation.

Seasonality and season of birth effect in the UK Biobank cohort.

OBJECTIVES: Humans live in environments that reduce the impact of seasonal cues. However, studies suggest that many aspects of human biology, such as birth, metabolism, health, and death are still annually rhythmic. METHODS: Using UK Biobank, a large (N = 502 536) population-based resource, we investigated the influence of seasonality on birth rate, basal metabolic rate, health, reaction speed, and sleep. We also investigated the association between season of birth and regional brain volumes, basal metabolic rate, health, reaction speed, and sleep. RESULTS: Our results showed that annual birth rate peaks in April and May. Individuals had the highest basal metabolic rate in December and January. Poorer subjective general health and slower reaction time were observed in May. Susceptibility to insomnia showed an opposite trend that peaked in autumn and winter. People reported shorter periods of sleep, easier waking, earlier chronotype, more daytime dozing, and napping in summer compared with winter. Our results suggest that season of birth may influence later-life characteristics. We also observed that the effect of season of birth is in the opposite direction of the seasonal rhythm for basal metabolic rate, reaction time, and insomnia. Moreover, our analysis showed that prevalence of allergy is higher among people born in spring compared to autumn. CONCLUSIONS: Overall, our findings indicate a significant effect of seasonality on a range of human traits and that early-life seasons appear to have an effect on health and behaviors in adulthood.

Hearing Impairment, Loneliness, Social Isolation, and Cognitive Function: Longitudinal Analysis Using English Longitudinal Study on Ageing.

OBJECTIVE: This study examines the relationships between hearing impairment and cognitive function among older adults, and whether that association is mediated by loneliness and social isolation. METHODS: Data were drawn from English Longitudinal Study of Ageing (ELSA) wave two (2004/2005) until wave seven (2014/2015). The study sample consisted of 8,199 individuals aged 50 years or older. Cognitive function was measured using episodic memory. We performed analysis using a generalized structural equation modeling (GSEM) technique. RESULTS: GSEM analysis shows that the direct effect of hearing impairment on episodic memory was negative and significant (ß = -0.29, p <0.001). Loneliness and social isolation mediated that effect. Hearing impairment was positively associated with loneliness (ß = 0.10, p <0.001) and social isolation (ß = 0.04, p <0.001). Loneliness (ß = -0.08, p <0.001) and social isolation (ß = -0.09, p = 0.001) were significantly associated with lower memory scores. CONCLUSION: The link between hearing impairment and episodic memory was partly mediated by loneliness and social isolation. Interventions to improve the social networks of older adults with hearing impairment are likely to be beneficial in preventing cognitive decline. Thus, the importance of maintaining social relationships among older adults, especially those with hearing impairment is highlighted.

No association between head injury with loss of consciousness and Alzheimer disease pathology-Findings from the University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age.

OBJECTIVES: Head injury with loss of consciousness (HI-LOC) is a common occurrence. Some studies have linked such injuries with an increased risk of Alzheimer disease (AD). However, recent large clinicopathologic studies have failed to find a clear relationship between HI-LOC and the pathological changes associated with AD. The present study aims to further investigate the relationship between HI-LOC and AD pathology in the elderly. METHODS/DESIGN: History of HI-LOC in participants in the University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age was ascertained. The donated brains of 110 of these individuals were assessed for AD pathology using consensus guidelines. Analyses aimed to elucidate relationships between HI-LOC and AD pathology. RESULTS: No associations were found between incidence of HI-LOC and regional AD pathology or any of the three established measures of the neuropathology associated with AD: CERAD score, Thal phase, or Braak stage. CONCLUSIONS: Single incidences of HI-LOC may not be sufficient to cause the pathology associated with late-stage AD. Other routes of damage, such as diffuse axonal injury or Lewy body pathology, may play a greater role in causing cognitive impairment associated with head injury.

Elevated luteinizing hormone despite normal testosterone levels in older men-natural history, risk factors and clinical features.

OBJECTIVE: Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L). DESIGN, PATIENTS AND MEASUREMENTS: We conducted a 4.3-year prospective observational study of 3369 community-dwelling European men aged 40-79 years. Participants were classified as follows: incident (i) HLH (n = 101, 5.2%); persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models. RESULTS: Age >70 years (OR = 4.12 [2.07-8.20]), diabetes (OR = 2.86 [1.42-5.77]), chronic pain (OR = 2.53 [1.34-4.77]), predegree education (OR = 1.79 [1.01-3.20]) and low physical activity (PASE ≤ 78, OR = 2.37 [1.24-4.50]) predicted development of HLH. Younger age (40-49 years, OR = 8.14 [1.35-49.13]) and nonsmoking (OR = 5.39 [1.48-19.65]) predicted recovery from HLH. Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, comorbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men. Men with HLH developed primary hypogonadism more frequently (OR = 15.97 [5.85-43.60]) than NLH men. Men with rHLH experienced a small rise in BMI. CONCLUSIONS: Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism.

Symptomatic androgen deficiency develops only when both total and free testosterone decline in obese men who may have incident biochemical secondary hypogonadism: Prospective results from the EMAS.

OBJECTIVE: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone-binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). DESIGN: Prospective observational study with a median follow-up of 4.3 years. PATIENTS: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. MEASUREMENTS: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. RESULTS: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. CONCLUSIONS: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT.

Patterns and severity of vascular amyloid in Alzheimer's disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer's disease.

In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vascular disease, we additionally aimed to explore the role of APOE genotype in CAA severity and subtypes. Plaque formation was greater in DS and missense APP mutations than in APPdup, sEOAD and sLOAD cases. Conversely, CAA was more severe in APPdup and missense APP mutations, and in DS, compared to sEOAD and sLOAD. When stratified by CAA subtype from 1 to 4, there were no differences in plaque scores between the groups, though in patients with APPdup, APP mutations and sEOAD, types 2 and 3 CAA were more common than type 1. Conversely, in DS, sLOAD and controls, type 1 CAA was more common than types 2 and 3. APOE ε4 allele frequency was greater in sEOAD and sLOAD compared to APPdup, missense APP mutations, DS and controls, and varied between each of the CAA phenotypes with APOE ε4 homozygosity being more commonly associated with type 3 CAA than types 1 and 2 CAA in sLOAD and sEOAD. The differing patterns in CAA within individuals of each group could be a reflection of variations in the efficiency of perivascular drainage, this being less effective in types 2 and 3 CAA leading to a greater burden of CAA in parenchymal arteries and capillaries. Alternatively, as suggested by immunostaining using carboxy-terminal specific antibodies, it may relate to the relative tissue burdens of the two major forms of Aß, with higher levels of Aß40 promoting a more 'aggressive' form of CAA, and higher levels of Aß42(3) favouring a greater plaque burden. Possession of APOE ε4 allele, especially ε4 homozygosity, favours development of CAA generally, and as type 3 particularly, in sEOAD and sLOAD.

Urinary incontinence and sexual health in a population sample of older people.

OBJECTIVES: To investigate the association between self-reported urinary incontinence (UI) and sexual health in a representative sample of older people. SUBJECTS AND METHODS: Participants were community-dwelling women and men aged 50-90+ years from the English Longitudinal Study of Ageing (ELSA) who reported any sexual activity in the last year. The prevalence of UI was assessed both cross-sectionally (ELSA Wave 6; 2012) and retrospectively over the preceding 8 years (ELSA Waves 2-6; 2004-2012). Sexual activities, difficulties and concerns were assessed using a validated Sexual Relationships and Activities Questionnaire. The association between UI and sexual health outcomes was examined using weighted logistic regressions, with adjustments made for demographic, health, and lifestyle factors. RESULTS: At Wave 6, 391 (20.0%) women and 141 (6.9%) men reported 'any UI' in the last 12 months. Compared to those without UI, women with UI reported declines in sexual activity and arousal over the last year, and increased concern about their frequency of sexual activity and ability to become sexually aroused. Men with 'any UI' reported declines in sexual desire, increased erectile and orgasm difficulties, and were more concerned about these sexual functions compared to men without UI. Differences in the patterns of association with sexual health were seen, dependent upon whether UI was reported as sporadic or persistent, and also with respect to the duration of retrospectively reported UI. CONCLUSION: Self-reported UI was associated with impairment in sexual health in women and men, and mainly linked to recent declines in sexual activity and function along with elevated sexual concerns. Our findings highlight that the sexual health of older people should be considered when managing UI.

Scores Obtained from a Simple Cognitive Test of Visuospatial Episodic Memory Performed Decades before Death Are Associated with the Ultimate Presence of Alzheimer Disease Pathology.

BACKGROUND: Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments. METHODS: The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Braak stage, was assessed by immunohistochemistry. Cognitive test scores collected 20 years prior to death were correlated with the extent of AD pathology present at death. RESULTS: Baseline scores from the Memory Circle test had the ability to distinguish between individuals who developed substantial AD pathology and those with no, or low, AD pathology. Predicted test scores at the age of 65 years also discriminated between these pathology groups. The addition of APOE genotype further improved the discriminatory ability of the model. CONCLUSIONS: The results raise the possibility of identifying individuals at future risk of the neuropathological changes associated with AD over 20 years before death using a simple cognitive test. This work may facilitate early interventions, therapeutics and treatments for AD by identifying at-risk and minimally affected (in pathological terms) individuals.

Dementia across local districts in England 2014 to 2015.

BACKGROUND: The number of older people needing dementia care is projected to rise rapidly, and local districts are now charged with responding to this need. But evidence on local area factors of dementia is scarce. We studied the odds of dementia prevalence and its individual risk factors enriched with area factors. MATERIALS AND METHODS: This study analysed objectively assigned dementia prevalence in people aged 60 and over living in community in England, drawing data from the English Longitudinal Study of Ageing 2014 to 2015 and local districts statistics using multilevel logistic models. Dementia status is ascertained using a modified version of the Telephone Interview for Cognitive Status. A number of individual risk factors were considered including social determinants, internet use, social connections, and health behaviours; 2 contextual factors were included: the index of multiple deprivation and land use mix. RESULTS: The prevalence of dementia by this method is 8.8% (95% confidence interval 7.7%-9.2%) in older adults in England. Maps of dementia prevalence across districts showed prevalent areas. In the full model, no area characteristics were significant in predicting dementia prevalence. Education, social connections, internet use, and moderate to vigorous physical activity showed protective associations. CONCLUSION: Dementia in older adults in England is largely predicted by individual characteristics, although some districts have a large share of their population with dementia. Given the health and social care costs associated with dementia, differential interventions and support to districts and to groups of individuals defined by these characteristics seem warranted.

Visual and hearing impairments are associated with cognitive decline in older people.

INTRODUCTION: highly prevalagent hearing and vision sensory impairments among older people may contribute to the risk of cognitive decline and pathological impairments including dementia.This study aims to determine whether single and dual sensory impairment (hearing and/or vision) are independently associated with cognitive decline among older adults and to describe cognitive trajectories according to their impairment pattern. MATERIAL AND METHODS: we used data from totals of 13,123, 11,417 and 21,265 respondents aged 50+ at baseline from the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE), respectively. We performed growth curve analysis to identify cognitive trajectories, and a joint model was used to deal with attrition problems in longitudinal ageing surveys. RESULTS: respondents with a single sensory impairment had lower episodic memory score than those without sensory impairment in HRS (ß = -0.15, P < 0.001), ELSA (ß = -0.14, P < 0.001) and SHARE (ß = -0.26, P < 0.001). The analysis further shows that older adults with dual sensory impairment in HRS (ß = -0.25, P < 0.001), ELSA (ß = -0.35, P < 0.001) and SHARE (ß = -0.68, P < 0.001) remembered fewer words compared with those with no sensory impairment. The stronger associations between sensory impairment and lower episodic memory levels were found in the joint model which accounted for attrition. CONCLUSIONS: hearing and/or vision impairments are a marker for the risk of cognitive decline that could inform preventative interventions to maximise cognitive health and longevity. Further studies are needed to investigate how sensory markers could inform strategies to improve cognitive ageing.

Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study.

BACKGROUND: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study. METHODS: The EMIF-AD 90+ Study aimed to enroll 80 cognitively normal subjects and 40 subjects with cognitive impairment aged 90 years or older. Cognitive impairment was operationalized as amnestic mild cognitive impairment (aMCI), or possible or probable Alzheimer's Disease (AD). The study was part of the European Medical Information Framework for AD (EMIF-AD) and was conducted at the Amsterdam University Medical Centers (UMC) and at the University of Manchester. We will test whether cognitive resilience is associated with cognitive reserve, vascular comorbidities, mood, sleep, sensory system capacity, physical performance and capacity, genetic risk factors, hallmarks of ageing, and markers of neurodegeneration. Markers of neurodegeneration included an amyloid positron emission tomography, amyloid ß and tau in cerebrospinal fluid/blood and neurophysiological measures. DISCUSSION: The EMIF-AD 90+ Study will extend our knowledge on resilience to cognitive impairment in the oldest-old by extensive phenotyping of the subjects and the measurement of a wide range of potential protective factors, hallmarks of aging and markers of neurodegeneration. TRIAL REGISTRATION: Nederlands Trial Register NTR5867 . Registered 20 May 2016.