The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 ...(calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65–90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.
•The influences of KIBRA and CLSTN2 SNPs on memory and hippocampal volume was studied.•No effect of KIBRA SNP or CLSTN2 SNP on memory or hippocampal volume.•No effect of KIBRA or CLSTN2 SNPs on hippocampal atrophy or memory decline.
Background with rationaleAlthough hospital admissions for epilepsy are common in people with intellectual disability (ID), little is known about the quality of inpatient care and outcomes after ...admission. To fill this gap, this project examines readmission, an important indicator for the quality of hospital care, and emergency department (ED) presentation after epilepsy admissions in people with ID compared to those without ID.
Main AimTo examine whether people with ID have a higher risk of all-cause readmissions and ED presentations after discharge from the index admission (i.e. first admission within the study period) for epilepsy than people without ID.
MethodsIn this retrospective data-linkage study, several linked administrative health datasets including but not restricted to hospital admissions, emergency department presentations, disability services and mental health ambulatory care are used to define the cohort, exposure and outcome. The cohort includes patients with and without ID who were admitted to hospital for epilepsy between 2002 and 2014 in New South Wales, Australia. The readmission rates and ED presentations within 28 days, 2-3 months, 4-6 months, and 7-12 months respectively will be compared between patients with and without ID. The effect of a diagnosis of ID on the risk of readmission and ED presentation within a year following the separation from the index admission will be estimated by Poisson regression.
Results and conclusionsThe demographics and comorbidity profile of participants at the index epilepsy admission will be presented. Readmission and ED presentation rates within each chunk of follow-up will be calculated by the status of ID and the incidence rate ratio will be provided to estimate the impact of ID on these outcomes. Findings will provide insight into how patients with ID and epilepsy fare in hospital care and help to guide future management of epilepsy in people with ID.
The distinction between dementia and mild cognitive impairment (MCI) relies upon the evaluation of independence in instrumental activities of daily living (IADL). Self- and informant reports are ...prone to bias. Clinician-based performance tests are limited by long administration times, restricted access, or inadequate validation. To close this gap, we developed and validated a performance-based measure of IADL, the Sydney Test of Activities of Daily Living in Memory Disorders (STAM).
Prospective cohort study (Sydney Memory and Ageing Study).
Eastern Suburbs, Sydney, Australia.
554 community-dwelling individuals (54% female) aged 76 and older with normal cognition, MCI, or dementia.
Activities of daily living were assessed with the STAM, administered by trained psychologists, and the informant-based Bayer-Activities of Daily Living Scale (B-ADL). Depressive symptoms were measured with the Geriatric Depression Scale (15-item version). Cognitive function was assessed with a comprehensive neuropsychological test battery. Consensus diagnoses of MCI and dementia were made independently of STAM scores.
The STAM showed high interrater reliability (r = 0.854) and test-retest reliability (r = 0.832). It discriminated significantly between the diagnostic groups of normal cognition, MCI, and dementia with areas under the curves ranging from 0.723 to 0.948. A score of 26.5 discriminated between dementia and nondementia with a sensitivity of 0.831 and a specificity of 0.864. Correlations were low with education (r = 0.230) and depressive symptoms (r = -0.179), moderate with the B-ADL (r = -0.332), and high with cognition (ranging from r = 0.511 to r = 0.594). The mean time to complete the STAM was 16 minutes.
The STAM has good psychometric properties. It can be used to differentiate between normal cognition, MCI, and dementia and can be a helpful tool for diagnostic classification both in clinical practice and research.
Hippocampal atrophy is observed with ageing and age-related neurodegenerative disease. Identification of the genetic correlates of hippocampal volume (HV) and atrophy may assist in elucidating the ...mechanisms of ageing and age-related neurodegeneration. Using two community cohorts of older Caucasians we estimated the heritability of HV and examined associations of HV with previously identified single nucleotide polymorphisms (SNPs). In addition we undertook genome-association studies (GWAS) examining HV and HV atrophy. Participants were community-dwelling non-demented older adults from the longitudinal Sydney Memory and Ageing Study (Sydney MAS) (N = 498) and the Older Australian Twins Study (OATS) (N = 351) aged 65 and over. HV was measured using T1-weighted magnetic resonance images. Heritability of HV was estimated in OATS. Genome-wide genotyping was imputed using the 1K Genomes reference set. Associations with HV-candidate and Alzheimer's disease (AD)-related SNPs were investigated. A GWAS examining HV (in both cohorts) and an exploratory GWAS of HV atrophy over two years (in Sydney MAS only) were also undertaken. HV heritability was estimated at 62-65%. The previously identified GWAS HV SNP (rs6581612) and the candidate BDNF SNP (rs6265) were nominally significant (p = 0.047 and p = 0.041 respectively). No AD-related SNPs, including the APOE ε4 polymorphism, were significant. No significant results were observed for either of the GWAS undertaken. Despite our estimate of a high heritability of HV, our results are consistent with a highly polygenic model suggesting that SNPs identified from prior studies, including GWAS meta-analyses, can be difficult to replicate in smaller samples of older adults.
Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to ...younger elders.
244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain "atrophy" and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were performed to determine structures that best discriminated aMCI from CN in individuals <85 and those ≥85 years.
aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN; such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and ≥85 age groups: cortex, putamen, parahippocampal, precuneus and superior frontal cortices in <85 years, and the hippocampus, pars triangularis and temporal pole in ≥85 years. Differences between naMCI and CN were small and non-significant in the sample. WMHs were not significantly associated with MCI subtypes.
Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly individuals. The structures that best distinguish aMCI from CN differ in those <85 from those ≥85, suggesting different neuropathological underpinnings of cognitive impairment in the very old.
Functional cognition is a relatively new concept in assessment of older adults with mild cognitive impairment or dementia. Instruments need to be reliable and valid, hence we conducted a systematic ...review of observational assessments of task performance used to estimate functional cognition in this population. Two separate database searches were conducted: firstly to identify instruments; and secondly to identify studies reporting on the psychometric properties of the instruments. Studies were analysed using a published checklist and their quality reviewed according to specific published criteria. Clinical utility was reviewed and the information formulated into a best evidence synthesis. We found 21 instruments and included 58 studies reporting on measurement properties. The majority of studies were rated as being of fair methodological quality and the range of properties investigated was restricted. Most instruments had studies reporting on construct validity (hypothesis testing), none on content validity and there were few studies reporting on reliability. Overall the evidence on psychometric properties is lacking and there is an urgent need for further evaluation of instruments.
: The aim of this article was to examine the prevalence and incidence over 2 years of mild cognitive impairment (MCI) in English speakers from linguistic minorities.
: Cross-sectional and ...longitudinal with 2-year follow-up.
: Eastern suburbs of Sydney, New South Wales, Australia.
: Eight hundred twenty-seven community-dwelling participants from English-speaking backgrounds (ESB) and 160 participants from non-English-speaking backgrounds (NESB) recruited through the electoral roll.
: Participants were assessed using 11 neuropsychological tests measuring memory, language, attention/processing speed, and executive function. Questionnaires measuring functional impairment and subjective cognitive complaints were completed by participants or informants.
: We found a two- to threefold higher prevalence of MCI in NESB participants than ESB participants depending on the impairment criterion applied. This difference was because of higher rates of objective cognitive impairment in NESB participants; rates of functional impairment and subjective cognitive complaints did not differ between the groups. This association between MCI prevalence and NESB status was accounted for by the proportion of time the participant spoke English and the proportion of life they had lived in Australia, but not by age, gender, and education. There were no differences between NESB and ESB groups in MCI incidence, dementia incidence, or rates of conversion from MCI to dementia. NESB participants had lower rates of reversion from MCI to normal.
: It is difficult to accurately diagnose MCI in persons from linguistic minority groups, even when proficient in English as neuropsychological test scores may not be valid for these groups. English language ability and level of acculturation should be considered when assessing older persons from ethnic minority groups.
•First meta-analysis on diet and incident depression in adults 45-years and older.•Pro-inflammatory and Western diets associated with increased risk of depression.•Higher fruit and vegetable intakes ...associated with reduce risk of depression.•Healthy and Mediterranean diets were not associated with depressive risk.
To systematically examine the longitudinal observational evidence between diet and the incidence of depression in adults aged 45 years and older.
Three electronic databases were searched for cohort studies published up to December 2020 that investigated the association between baseline dietary intake and incidence of depression in community-dwelling adults aged 45+years. Combined odds ratios (OR) and 95% confidence intervals (95%CI) were calculated. Random-effects models were used.
In total 33 articles were included, with 21 combined in meta-analyses. Both the Dietary Inflammatory Index and the Western diet were associated with an increased odds of incident depression (Dietary Inflammatory Index: OR 1.33; 95%CI 1.04, 1.70; P = 0.02; Western: OR 1.15 95%CI 1.04, 1.26; P = 0.005). Higher fruit and vegetable intakes were associated with a reduced risk of incident depression (vegetables: OR 0.91; 95%CI 0.87, 0.96; P < 0.001; fruit: OR 0.85; 95%CI 0.81, 0.90; P < 0.001). No association was observed between the Mediterranean diet, “healthy” diet, fish intake and incident depression.
Results suggest an association between higher consumption of pro-inflammatory diets and Western diets and increased incidence of depression, while higher intake of fruit and vegetables was associated with decreased incidence of depression. These results are limited by the observational nature of the evidence (results may reflect residual confounding) and the limited number of studies. More high-quality intervention and cohort studies are needed to confirm these associations and to extend this work to other food groups and dietary patterns.
Abstract Background Education, a marker for cognitive reserve, is thought to be associated with low risks of dementia, but less is known about its association with cognitive decline in preclinical ...stages of dementia. This study aimed to see whether higher education level could have a protective effect against faster cognitive decline in preclinical stages of dementia and whether this protection is consistent across six different studies around the world. Methods We assessed the association between education and change in mini-mental state examination (MMSE) in people who developed dementia during the study period before the time of dementia diagnosis in six international studies of ageing: Newcastle 85+, UK; Three-City (3C), France; Leiden 85+ and Longitudinal Aging Study Amsterdam (LASA), the Netherlands; Octogenarian Twins (OCTO-Twin), Sweden; and Memory and Ageing Study (MAS), Australia. Using a coordinated analysis approach, we used multilevel models to investigate the role of education in the change in MMSE independently within each cohort, while controlling for common covariates such as age at baseline, sex, and time to dementia diagnosis from study entry within each cohort. Each individual's cognitive scores were aligned according to distance (years) to dementia diagnosis. Findings High levels of education (>12 years) were associated with steeper linear rates of decline in MMSE scores from study entry to time of dementia diagnosis in most cohorts—3C, Leiden 85+, LASA, OCTO-Twin, and MAS. However, in one cohort (Newcastle 85+), higher education was associated with a slow rate of decline in the preclinical stages of dementia (β=0·93, 95% CI 0·09–1·77) compared with lower education, suggesting perhaps a difference in the educational system between the UK and the rest of Europe or Australia during the early 1990s. A random-effects meta-analysis across data from all six studies showed a non-significant steeper cognitive decline with time for those with higher education (β=–0·08, 95% CI –0·17 to 0·003; see appendix for forest plot). Interpretation This coordinated approach analysis revealed no consistent protection for people with higher education in terms of lowering the rate of cognitive decline in the preclinical stages of dementia, which is a major public health burden. This work only partly supports the cognitive reserve hypothesis—ie, the clinical manifestation of dementia is delayed in people with higher education but that a steeper decline occurs once a certain threshold has been reached. Funding The funding sources of this work were the Alzheimer's Society (grant number 144) and the Medical Research Council (unit programme number MC_UU_12019/1).
Background: It is well established that people with an intellectual disability have high rates of mental health problems, yet rates of uptake of services do not match need. Aim: To identify the ...current literature pertaining to the barriers and facilitators to access to mental health services for people with an intellectual disability. Method: A systematic search identified English-language articles that addressed barriers or enablers to access, mental health services, and intellectual disability from 2005 to 2016. Results were synthesized according to Gulliford et al.'s four dimensions of access: availability, utilization, relevance and effectiveness, and equity. Results: Barriers and enablers were identified across all the dimensions. Organizational barriers, lack of services, and poor-quality services related to deficits in knowledge were among the barriers discussed in the literature. Facilitators included emphasis on interagency collaboration, and training and education. Substantial gaps were also identified, particularly in relation to the lived experience of these barriers. Conclusions: Further research and evaluation across all aspects of access to mental health care for people with an intellectual disability is needed.
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