The APOE paradox: how do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Possession of an APOE e4 allele is an established risk factor for Alzheimer’s disease, while the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. 66 volunteers, aged 45-55 years, completed three tasks that provided complementary measures of attentional control: prospective memory, sustained attention and inhibition. Performance was compared between e2 carriers, e4 carriers and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared to the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes

Diabetic Peripheral Microvascular Complications: Relationship to Cognitive Function

Peripheral microvascular complications in diabetes are associated with concurrent cerebrovascular disease. As detailed cognitive assessment is not routinely carried out among diabetic patients, the aim was to establish whether the presence of clinical “peripheral” microvascular disease can identify a subgroup of patients with early evidence of cognitive impairment. Detailed psychometric assessment was performed in 23 diabetic patients with no microvascular complications (Group D), 27 diabetic patients with at least one microvascular complication: retinopathy, neuropathy, and/or nephropathy (Group DC), and 25 healthy controls (Group H). Groups D and DC participants had significantly lower scores on reaction time (P = 0.003 and 0.0001, resp.) compared to controls. Similarly, groups D and DC participants had significantly lower scores on rapid processing of visual information (P = 0.034 and 0.001, resp.) compared to controls. In contrast, there was no significant difference between Groups D and DC on any of the cognitive areas examined. The results show that diabetes, in general, is associated with cognitive dysfunction, but the additional presence of peripheral microvascular disease does not add to cognitive decline. The study, however, indirectly supports the notion that the aetiology of cognitive impairment in diabetes may not be restricted to vascular pathology

The elusive nature of APOE ε4 in mid-adulthood: understanding the cognitive profile

Objectives: The apolipoprotein E (APOE) ε4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This study undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable. Methods: Thirty-six papers investigating the behavioral effects of APOE ε4 in mid-adulthood (defined as a mean sample age between 35 and 60 years) were reviewed. In addition, the effect of carrying an ε4 allele on individual cognitive domains was assessed in separate meta-analyses. Results: The average effect size of APOE ε4 status was non-significant across cognitive domains. Further consideration of genotype effects indicates preclinical effects of APOE ε4 may be observable in memory and executive functioning. Conclusions: The cognitive profile of APOE ε4 carriers at mid-age remains elusive. Although there is support for comparable performance by ε4 and non-e4 carriers in the 5th decade, studies administering sensitive cognitive paradigms indicate a more nuanced profile of cognitive differences. Methodological issues in this field preclude strong conclusions, which future research must address, as well as considering the influence of further vulnerability factors on genotype effects

Co-creating connected and intelligent care homes for people with dementia

Connected Care aims to address three main challenges that care homes face with regards to people living with dementia 1. Care homes are increasingly challenged by a rising number of people living with dementia and a simultaneous demand to improve quality of care amidst limited funding and staff shortages. 2. Although innovation is associated with better quality of care, there is limited research looking into the ways in which digital technology, including the Internet of Things and sensors, could help care homes deliver better care for people with dementia. 3. Scholarly research has highlighted that top-down implementations of technology fail to deliver their potential benefits when there is limited user buy-in. In the context of care homes, care workers, residents and their families are often under-represented in technological developments

Social networks and loneliness in people with Alzheimer's dementia

Objectives Modifiable lifestyle risk factors are of great interest in the prevention and management of Alzheimer's disease (AD). Loneliness and social networks may influence onset of AD, but little is known about this relationship in people with AD. The current study aimed to explore the relationship between loneliness and social networks (social measures) and cognitive and psychopathology decline (AD outcomes) in people with AD. Methods Ninety‐three participants with mild‐moderate AD were recruited from memory clinics, in a cross‐sectional study. Social networks (measured by the Lubben Social Network Scale), feelings of loneliness (measured by De Jong Loneliness Scale), cognition (measured by the Standardized Mini Mental State Examination) and psychopathology (measured by the Neuropsychiatric Inventory) were assessed in an interview setting. Two multiple regressions with Bootstrap were conducted on cognition and psychopathology as outcome variables. Family and Friends subsets of social networks and loneliness were entered as predictors and age, gender and depression as covariates. Results The friendship subset of social networks was significantly related to cognition (independent of age, gender, depression, loneliness and family subset of social network): B = .284, p = .01. Neither loneliness nor social networks predicted psychopathology (ps > .05). Conclusions Maintaining or developing a close friendship network could be beneficial for cognition in people with AD. Alternatively, greater dementia severity may lead to fewer friends. More research on the direction of this relationship in people with AD is needed

Homocysteine concentrations in the cognitive progression of Alzheimer’s disease

Objectives: Hyperhomocysteinemia in Alzheimer’s disease (AD) is widely reported and appears to worsen as the disease progresses. While active dietary intervention with vitamins B12 and folate decreases homocysteine blood levels, with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far has not been replicated in established AD populations. The aim of the study is to explore the relationship between hyperhomocystenemia and relevant vitamins as the disease progresses. Methods: In this longitudinal cohort study, 38 participants with mild to moderate AD were followed for an average period of 13 months. Plasma folate, vitamin B12 and homocysteine concentrations were measured at baseline and at follow-up. Dietary intake of B vitamins was also measured. Spearman’s correlations were conducted by homocysteine and B vitamin status. Results: As expected, cognitive status significantly declined over the follow-up period and this was paralleled by a significant increase in homocysteine concentrations (p=0.006). However, during this follow-up period there was no significant decline in neither dietary intake, nor the corresponding blood concentrations of vitamin B12/folate, with both remaining within normal values. Changes in blood concentrations of B vitamins were not associated with changes in homocysteine levels (p>0.05). Conclusion: In this study, the increase in homocysteine observed in AD patients as the disease progresses cannot be solely explained by dietary and blood levels of folate and vitamin B12. Other dietary and non-dietary factors may contribute to hyperhomocysteinemia and its toxic effect in AD, which needs to be explored to optimise timely intervention strategies

Psychometric properties and feasibility of use of dementia specific quality of life instruments for use in care settings: a systematic review

Background: Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings. Design: Systematic review. Methods: Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review. Results: Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use. Conclusions: Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible

Adaptation of the DEMQOL-Proxy for routine use in care homes: a cross sectional study of the reliability and validity of DEMQOL-CH

Objective: To investigate the routine use of a measure of quality of life (QoL) in care homes and assess its psychometric properties when used by care staff Design: A cross-sectional two-phase study. Setting and participants: Data were collected from care staff in seven care homes in East Sussex, England. Method: Phase 1: The ability of care staff from two care homes to use the DEMQOL-Proxy without interviewer-administration was assessed using agreement analysis between a selfand interviewer-administered version of the instrument. Based on these findings, DEMQOLProxy was adapted into a new version, DEMQOL-CH, for use as a self-administered instrument in care homes. We assessed agreement between the new DEMQOL-CH and DEMQOL-Proxy to ensure DEMQOL-CH was used correctly. Phase 2: A preliminary assessment of the psychometric properties of DEMQOL-CH when used routinely was completed in a further five care homes. Results: Phase 1: Nineteen care staff from two care homes completed QoL measurements for residents. Systematic error was identified when staff self-completed the DEMQOL-Proxy without an interviewer. We modified the DEMQOL-Proxy to create DEMQOL-CH; this reduced the error, producing a version that could be used more accurately by care staff. Phase 2: Eleven care staff from five care homes rated resident QoL routinely. DEMQOL-CH showed acceptable psychometric properties with satisfactory reliability and validity and a clear factor structure. Conclusions: The research presents positive preliminary data on the acceptability, feasibility and performance of routine QoL measurement in care homes using an adapted version of DEMQOL-Proxy, the DEMQOL-CH. Results provide evidence to support the concept that routine measurement of QoL may be possible in care homes. Research is needed to refine and test the methodology and instrument further, and to explore the potential for benefits to residents, staff, and care homes in larger and more representative populations

Bilingualism: a global public health strategy for healthy cognitive aging

Dementia is a global public health priority which cost global societies $818 billion in 2015 and is disproportionately impacting low and middle-income countries (LMICs). With limited availability of disease modifying drugs to treat Alzheimer's disease (AD), researchers have increasingly focused on preventative strategies which may promote healthy cognitive aging and mitigate the risk of cognitive impairment in aging. Lifelong bilingualism has been presented as both a highly debated and promising cognitive reserve factor which has been associated with better cognitive outcomes in aging. A recent metanalysis has suggested that bilingual individuals present on average 4.05 years later with the clinical features of AD than monolinguals. Bilinguals are also diagnosed with AD ~2.0 years later than monolingual counterparts. In this perspective piece we critically evaluate the findings of this metanalysis and consider the specific implications of these findings to LMICs. Furthermore, we appraise the major epidemiological studies conducted globally on bilingualism and the onset of dementia. We consider how both impactful and robust studies of bilingualism and cognition in older age may be conducted in LMICs. Given the limited expenditure and resources available in LMICs and minimal successes of clinical trials of disease modifying drugs we propose that bilingualism should be positioned as an important and specific public health strategy for maintaining healthy cognitive aging in LMICs. Finally, we reflect upon the scope of implementing bilingualism within the education systems of LMICs and the promotion of bilingualism as a healthy cognitive aging initiative within government policy

Vitamin E for Alzheimer's dementia and mild cognitive impairment

Background Vitamin E occurs naturally in the diet. It has several biological activities, including functioning as an antioxidant to scavenge toxic free radicals. Evidence that free radicals may contribute to the pathological processes behind cognitive impairment has led to interest in the use of vitamin E supplements to treat mild cognitive impairment (MCI) and Alzheimer's disease (AD). This is an update of a Cochrane Review first published in 2000, and previously updated in 2006 and 2012. Objectives To assess the efficacy of vitamin E in the treatment of MCI and dementia due to AD. Search methods We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources on 22 April 2016 using the terms: "Vitamin E", vitamin‐E, alpha‐tocopherol. Selection criteria We included all double‐blind, randomised trials in which treatment with any dose of vitamin E was compared with placebo in people with AD or MCI. Data collection and analysis We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. Where appropriate we attempted to contact authors to obtain missing information. Main results Four trials met the inclusion criteria, but we could only extract outcome data in accordance with our protocol from two trials, one in an AD population (n = 304) and one in an MCI population (n = 516). Both trials had an overall low to unclear risk of bias. It was not possible to pool data across studies owing to a lack of comparable outcome measures. In people with AD, we found no evidence of any clinically important effect of vitamin E on cognition, measured with change from baseline in the Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) over six to 48 months (mean difference (MD) ‐1.81, 95% confidence interval (CI) ‐3.75 to 0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no evidence of a difference between vitamin E and placebo groups in the risk of experiencing at least one serious adverse event over six to 48 months (risk ratio (RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1 study, n = 304; moderate quality evidence). People with AD receiving vitamin E showed less functional decline on the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory than people receiving placebo at six to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study, n = 280; moderate quality evidence). There was no evidence of any clinically important effect on neuropsychiatric symptoms measured with the Neuropsychiatric Inventory (MD ‐1.47, 95% CI ‐4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate quality evidence). We found no evidence that vitamin E affected the probability of progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95% CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five deaths occurred in each of the vitamin E and placebo groups over the 36 months (RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality evidence). We were unable to extract data in accordance with the review protocol for other outcomes. However, the study authors found no evidence that vitamin E differed from placebo in its effect on cognitive function, global severity or activities of daily living . There was also no evidence of a difference between groups in the more commonly reported adverse events. Authors' conclusions We found no evidence that the alpha‐tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD. However, there is moderate quality evidence from a single study that it may slow functional decline in AD. Vitamin E was not associated with an increased risk of serious adverse events or mortality in the trials in this review. These conclusions have changed since the previous update, however they are still based on small numbers of trials and participants and further research is quite likely to affect the results