Primary fatty amides in plasma associated with brain amyloid burden,hippocampal volume,and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

IntroductionA critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.MethodsThis study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.ResultsEight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.DiscussionPFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.     

Longitudinal analysis of dementia diagnosis and specialty care among racially diverse Medicare beneficiaries

IntroductionThere is insufficient understanding of diagnosis of etiologic dementia subtypes and contact with specialized dementia care among older Americans.MethodsWe quantified dementia diagnoses and subsequent health care over five years by etiologic subtype and physician specialty among Medicare beneficiaries with incident dementia diagnosis in 2008/09 (226,604 persons/714,015 person-years).ResultsEighty-five percent of people were diagnosed by a nondementia specialist physician. Use of dementia specialists within one year (22%) and five years (36%) of diagnosis was low. “Unspecified” dementia diagnosis was common, higher among those diagnosed by nondementia specialists (33.2%) than dementia specialists (21.6%). Half of diagnoses were Alzheimer's disease.DiscussionAscertainment of etiologic dementia subtype may inform hereditary risk and facilitate financial and care planning. Use of dementia specialty care was low, particularly for Hispanics and Asians, and associated with more detection of etiological subtype. Dementia-related professional development for nonspecialists is urgent given their central role in dementia diagnosis and care.     

Carer preferences for home support services in later stage dementia

Objectives: To examine the relative importance of different home support attributes from the perspective of carers of people with later-stage dementia.

Method: Preferences from 100 carers, recruited through carers’ organisations, were assessed with a Discrete Choice Experiment (DCE) survey, administered online and by paper questionnaire. Attributes were informed by an evidence synthesis and lay consultations. A conditional logit model was used to estimate preference weights for the attributes within a home support ‘package’.

Results: The most preferred attributes were ‘respite care, available regularly to fit your needs’ (coefficient 1.29, p = < 0.001) and ‘home care provided regularly for as long as needed’ (coefficient 0.93, p = < 0.001). Cost had a significant effect with lower cost packages preferred. Findings were similar regardless of the method of administration, with respite care considered to be the most important attribute for all carers. Carers reported that completing the DCE had been a positive experience; however, feedback was mixed overall.

Conclusions: These carer preferences concur with emerging evidence on home support interventions for dementia. Respite care, home care and training on managing difficulties provided at home are important components. Carers’ preferences revealed the daily challenges of caring for individuals with later stage dementia and the need for tailored and specialised home support.     

The effect of remotely delivered lifestyle interventions on cognition in older adults without dementia: A systematic review and meta-analysis

Up to 40% of dementias may be preventable via risk factor modification. This inference has motivated the development of lifestyle interventions for reducing cognitive decline. Typically delivered to older adults face-to-face, the COVID-19 pandemic has necessitated their adaptation for remote delivery. We systematically reviewed randomized controlled trials of remotely delivered lifestyle interventions (≥4 weeks duration and delivered >50% remotely), for adults aged ≥ 60 without dementia, examining effects on objective cognitive measures. Comparators were active (face-to-face or remote) or passive. Ten studies (n = 2967) comprising multidomain (k = 4), physical activity (k = 3) or psychosocial (k = 3) remote interventions were included. Data were synthesized using robust variance estimation meta-analysis. The pooled estimate comparing the effect of remote interventions versus comparators on cognition was not significant (g=−0.02; 95%CI [−0.14, 0.09]; p = .66); subgroup analyses by type of intervention or comparator also yielded non-significant effects. Most studies had low risk of bias. Current evidence to support remote lifestyle interventions is limited. Included studies were conducted pre-pandemic, and evaluated individual, rather than group interventions. Future studies may exploit the greater digital connectivity of older people since the pandemic. Group formats, more frequently efficacious than individual interventions in face-to-face dementia prevention trials, may be a rational approach for future remote trials.     

Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review

BackgroundDementia is a debilitating syndrome that significantly impacts individuals over the age of 65 years. There are currently no disease-modifying treatments for dementia. Impairment of nutrient sensing pathways has been implicated in the pathogenesis of dementia, and may offer a novel treatment approach for dementia.AimsThis systematic review collates all available evidence for Food and Drug Administration (FDA)-approved therapeutics that modify nutrient sensing in the context of preventing cognitive decline or improving cognition in ageing, mild cognitive impairment (MCI), and dementia populations.MethodsPubMed, Embase and Web of Science databases were searched using key search terms focusing on available therapeutics such as ‘metformin’, ‘GLP1’, ‘insulin’ and the dementias including ‘Alzheimer’s disease’ and ‘Parkinson’s disease’. Articles were screened using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). The risk of bias was assessed using the Cochrane Risk of Bias tool v 2.0 for human studies and SYRCLE’s risk of bias tool for animal studies.ResultsOut of 2619 articles, 114 were included describing 31 different ‘modulation of nutrient sensing pathway’ therapeutics, 13 of which specifically were utilized in human interventional trials for normal ageing or dementia. Growth hormone secretagogues improved cognitive outcomes in human mild cognitive impairment, and potentially normal ageing populations. In animals, all investigated therapeutic classes exhibited some cognitive benefits in dementia models. While the risk of bias was relatively low in human studies, this risk in animal studies was largely unclear.ConclusionsModulation of nutrient sensing pathway therapeutics, particularly growth hormone secretagogues, have the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.     

Risk factors for falls in older people with cognitive impairment living in the community: Systematic review and meta-analysis

PurposeThis systematic review aimed to identify risk factors for prospectively ascertained falls, focusing on those that are potentially modifiable (physical and neuropsychological factors), in older people with cognitive impairment living in the community.ResultsA comprehensive search of five databases identified 16 high quality (Newcastle-Ottawa Scale ≥8/9) relevant articles. Meta-analyses were undertaken for five potential fall risk factors. Of these, fallers had significantly poorer balance (standardized mean difference = 0.62, 95 %CI 0.45, 0.79) with low heterogeneity. Global cognition was not significantly associated with faller status in a meta-analysis with low heterogeneity. Meta-analyses of mobility (Timed Up-and-Go), gait speed and depressive symptoms had high heterogeneity and were not statistically significant or were borderline significant (p = 0.05). Sensitivity analyses (removing one study sample’s results that differed markedly from the other included samples) reduced heterogeneity to 0% and revealed fallers had significantly poorer mobility and more depressive symptoms than non-fallers. Fallers also walked significantly slower, but heterogeneity remained high.ConclusionsIn older people with cognitive impairment, fallers presented with balance deficits, poor mobility, slow gait speed and depressive symptoms. Reduced global cognition was not associated with falls. These findings suggest that interventions should target balance impairment and reveal that more high-quality research is needed.     

Risk of seizures and subclinical epileptiform activity in patients with dementia: A systematic review and meta-analysis

BackgroundSeizures and subclinical epileptiform activity are common yet easily overlooked among demented patients. We aimed to investigate their epidemiological characteristics in patients with dementia from various aspects.MethodsWe retrieved relevant observational studies from PubMed and Embase Library until March 2021. Pooled estimate effects were calculated using random-effects models. This study is registered with PROSPERO, number CRD42020200949.ResultsOf the 19144 identified studies, 27 were eligible for inclusion. The pooled period prevalence rates of seizures were 4.86% (95%CI: 3.43–6.51%), 2.68% (95%CI: 2.13–3.28%), 2.81% (95%CI: 2.02–3.71%）and 7.13% (95%CI: 2.67–13.14%) among patients with Alzheimer’s disease (AD), Dementia of Lewy Body (DLB), Frontotemporal dementia (FTD) and Vascular dementia (VaD), respectively. The pooled incidence rate of seizures was [8.4 (95%CI: 4.2–12.7) per 1000 person-years] in AD patients. And the pooled relative risk of seizures in patients with AD was 3.35 (95%CI: 2.69–4.19). Besides, the pooled cumulative incidence rate and prevalence rate of subclinical epileptiform activity among AD patients were [21.41% (95%CI: 0.001–63.60%)] and 9.73% (95%CI: 0.26–28.38%), respectively.ConclusionsThe accurate rates of seizures and subclinical epileptiform activities in the four major dementia types are high. Besides, patients with AD are likely at a higher risk of seizures.