Delay Cognitive Decline Research Articles

Late-onset caloric restriction improves cognitive performance and restores circadian patterns of neurotrophic, clock and epigenetic factors in the hippocampus of male old rats.

Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.

Multimorbidity patterns, leisure activities, and cognitive function: A population-based longitudinal study

Abstract Background There is limited knowledge about the effect of leisure activities on cognitive decline related to different multimorbidity patterns. The study aimed to examine the role of leisure activities in the association between multimorbidity patterns and cognitive function. Methods We conducted a community-based cohort study based on the 2002-2018 Chinese Longitudinal Health Longevity Survey (CLHLS). Multimorbidity patterns were examined by exploratory factor analysis. Multivariable linear and logistic regression models were used to assess the associations between multimorbidity, leisure activities and cognitive function. Results The study included 14,093 older adults. Those with specific multimorbidity patterns had lower MMSE scores. Compared to individuals with cardio-metabolic and sensory patterns who frequently engaged in activities such as housework, garden work, and watching TV/listening to the radio, those who participated in these activities less regularly had lower MMSE scores. Furthermore, a higher frequency change of participation and a greater variety of leisure activities were associated with better cognitive function. Conclusions The older individuals with multimorbidity are associated with lower MMSE scores, while those who participated in more leisure activities had higher cognitive function. Diverse, and frequent leisure activities may help delay cognitive decline in Chinese older adults with different multimorbidities.

Dietary Choline Intake Is Beneficial for Cognitive Function and Delays Cognitive Decline: A 22-Year Large-Scale Prospective Cohort Study from China Health and Nutrition Survey.

Pre-clinical studies have discovered the neuroprotective function and the benefit for cognitive function of choline. However, it remains unclear whether these benefits observed in animal studies also work in humans. The aims of this study are to examine the effects of dietary choline intake on cognitive function and cognitive decline during ageing in middle-aged and elderly Chinese. We included 1887 subjects aged 55~79 years with 6696 observations from the China Health and Nutrition Survey cohort study. The subjects were followed up for 6 to 21 years, with an average of 12.2 years. A dietary survey was conducted over 3 consecutive days with a 24 h recall, using household weight-recording methods. Based on the China Food Composition, data from USDA, and published literature, the dietary choline intake was calculated as the sum of free choline, phosphocholine, phosphatidylcholine, sphingomyelin, and glycerophosphocholine. Cognitive function was assessed using a subset of the Telephone Interview for Cognitive Status-modified (TICS-m) items. In order to eliminate the different weight of scores in each domain, the scores were converted by dividing by the maximum score in each domain, which ranged from 0 to 3 points. Higher cognitive scores represented better cognition. We used two-level mixed effect models to estimate the effects of dietary choline intake on cognitive score and cognitive decline rate in males and females, respectively. The average dietary choline intake was 161.1 mg/d for the baseline. After adjusting for confounders, the dietary choline intake was significantly associated with higher cognitive score in both males and females. The cognitive score in the highest quartile group of dietary choline was 0.085 for males and 0.077 for females-higher than those in the lowest quartile group (p < 0.01 for males, p < 0.05 for females). For every 10-year increase in age, the cognitive score decreased by 0.266 for males and 0.283 for females. The cognitive score decline rate of the third quartile group of dietary choline was 0.125/10 years lower than that of the lowest quartile group in females (p < 0.05). Dietary choline intake not only improves cognitive function, but also postpones cognitive decline during the aging process. The findings of this study highlight the neuroprotective benefit of choline in the middle-aged and elderly Chinese population, especially among females.

Cognitive reserve involves decision making and is associated with left parietal and hippocampal hypertrophy in neurodegeneration

Cognitive reserve is the ability to actively cope with brain deterioration and delay cognitive decline in neurodegenerative diseases. It operates by optimizing performance through differential recruitment of brain networks or alternative cognitive strategies. We investigated cognitive reserve using Huntington’s disease (HD) as a genetic model of neurodegeneration to compare premanifest HD, manifest HD, and controls. Contrary to manifest HD, premanifest HD behave as controls despite neurodegeneration. By decomposing the cognitive processes underlying decision making, drift diffusion models revealed a response profile that differs progressively from controls to premanifest and manifest HD. Here, we show that cognitive reserve in premanifest HD is supported by an increased rate of evidence accumulation compensating for the abnormal increase in the amount of evidence needed to make a decision. This higher rate is associated with left superior parietal and hippocampal hypertrophy, and exhibits a bell shape over the course of disease progression, characteristic of compensation.

ASSOCIATION BETWEEN LATE LIFE EDUCATION AND COGNITIVE FUNCTION AMONG U.S. OLDER ADULTS

Abstract This study assessed whether late-life education (LLE) was associated with better cognitive function and whether the benefits of LLE on cognitive decline differed by gender, race/ethnicity, and education level in a nationally-representative sample of U.S. older adults. We conducted a retrospective cohort study using six waves of data from the Health and Retirement Study ([HRS] 2008-2018) that included adults aged ≥ 65 with no baseline diagnosis of Alzheimer’s disease and related dementias (ADRD). Cognitive function was measured at baseline and over time using a summary score that included immediate/delayed word recall, serial 7’s test, objective naming test, backwards counting, recall of the current date, and naming the president/vice-president (range=0-35). LLE was measured at every wave and was categorized as “once a month or more,” and “not in the last month [or never].” Covariates included participants’ demographic background, socioeconomic status, psychosocial and behavioral factors, and health-related factors. Of 12,099 participants (median age 71 [IQR=10]), engaging in LLE at least once a month or more was associated with better cognitive function and was equivalent to a 2-4 year delay in cognitive decline than non-participation in LLE. The association was only partially attenuated after adjusting for a wide range of covariates. In addition, the benefits of LLE on cognitive function did not significantly differ by gender, race/ethnicity, or prior educational attainment. This study provides new insights into the protective role of LLE on cognitive function and underscores the importance of continued learning among older adults.

Associations of multilingualism and language proficiency with cognitive functioning: epidemiological evidence from the SwissDEM study in community dwelling older adults and long-term care residents

BackgroundWe explored whether number of languages spoken and language proficiency are associated with cognitive performance among older adults living in the community and in long-term care (LTC) in Switzerland.MethodsAmong study participants, 664 lived in the community in the Canton of Zurich (Mean age = 72.97 years; SD = 6.08), 386 lived in the community in Ticino (Mean age = 76.24 years; SD = 6.66), and 176 resided in LTC in Ticino (Mean age = 87.61 years; SD = 6.45). We recorded sociodemographic variables, number of languages spoken, language proficiency, and assessed overall cognitive performance, immediate and delayed memory, and verbal fluency with standardized tests. We used adjusted regression models.ResultsA higher number of spoken languages was positively associated with overall cognitive performance, verbal fluency and immediate and delayed memory performance in community-dwelling older adults in the Cantons of Ticino and Zurich, (all p values ≤ 0.012;), but not in in older adults living in LTC homes (all p values ≥ 0.35). Higher language proficiency was associated with better memory performance among individuals living in the community in Ticino (p value = 0.003), and to better performance in verbal fluency and memory tasks in Zurich (p values ≤ 0.002). Among LTC residents, proficiency levels were not associated with cognitive performance.ConclusionsMultilingualism and greater language proficiency were associated with better cognitive functioning in community-dwelling but not in institutionalized older adults. Multilingualism may contribute to cognitive reserve, as well as protect and delay cognitive decline in late life.

Cognitive function and hearing loss: A longitudinal investigation of the effect of hearing aid use on cognitive performance in older adults

AbstractBackgroundHearing loss is highly prevalent in older adults and has been identified as the largest single potentially modifiable risk factor for dementia. Although hearing aids are a successful treatment for hearing loss, it is unknown whether their use can delay the onset of cognitive decline or improve cognitive function. Less than 20% of adults who would benefit from hearing aids actually using them. Results at 18‐ and 36‐months post‐hearing aid fitting in this prospective Australian longitudinal study will be presented.MethodParticipants were assessed before and every 18 months after hearing aid fitting. Results were compared with those of a control group of participants of a cohort study of aging in older adults (AIBL) and also with a large normative group using the cognitive assessment tool. Assessments included cognitive function (visually presented computerized assessment battery), hearing, speech perception, quality of life, activity, diet, loneliness and isolation, anxiety, depression, medical health, and genetic riskResultAfter 18 months of hearing aid use there was no significant cognitive decline for hearing aid participants, and group mean scores for executive function significantly improved, with stability or improvement for 92%. Comparative group results showed no improvement at 18 months. At 36‐month follow‐up, after almost 18 months of repeated COVID lockdowns, hearing aid use had decreased, and loneliness had increased. The previously observed improvement in executive function was no longer evident, but performance on 4/5 subtests remained stable.ConclusionThis is the first study to follow participants for this length of time. After 36 months of hearing aid use, most participants had remained stable, and a subset had improved cognitive function. These results suggest that hearing aid use may not only delay cognitive decline but could improve cognitive function. This study will continue to investigate whether cognitive function could continue to improve for some participants, and the longer‐term trajectory of effects of hearing aid use.

Evaluation of a comprehensive multicomponent support program for people with dementia and their carers: Study protocol for pilot trial

AbstractBackgroundA growing body of evidence demonstrates the importance of comprehensive multicomponent, person‐centred interventions, including education and support for people living with dementia and their carers following a diagnosis of dementia. However, in Australia, people with dementia and carers frequently face challenges accessing appropriate information, care and support services to support living in the community with different stages of dementia.MethodThe Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) program consists of evidence‐based therapeutic activities for people with dementia and carers. The project aims to recruit 24 dyads (24 people with dementia and 24 carers; four groups of six) to participate in a twelve‐week, twice per week support program using a randomised waiting‐list study design. The SPICE program intervention is delivered by allied health professionals and includes physical activity, cognitive stimulation therapy, and nutrition assessment for the person with dementia. Carers will receive support aimed to promote capacity building and self‐care, including practical strategies to manage behavioural changes. The dyad will also receive the Care of People with Dementia in their Environments (COPE) program which focuses on problem solving and goal setting in the home.ResultThe primary outcome for the intervention is quality of life of the person with dementia using the health‐related quality of life (DEMQOL) questionnaire. Secondary outcomes will assess cognition (Addenbrookes Cognitive Examination (ACE‐III)), neuropsychiatric symptoms (NPI), health and functional ability (WHODAS 2.0), physical function assessments, carer quality of life (C‐DEMQOL), and program satisfaction of the dyad. Categorical data will be summarised using frequency statistics and visualisation. Continuous and other numerical data will be visually explored and summarised using sample descriptive statistics, selected as appropriate based on apparent distributions.ConclusionThe SPICE program has the potential to promote quality of life of people with dementia and potentially delay cognitive decline while also providing a toolkit for carers to reduce carer burden. If successful, the outcomes of the study have the potential to improve post‐diagnostic care and clinical practice for people with dementia and their carers in Australia and inform services worldwide.

FDG PET (and MRI) for Monitoring Immunotherapy in Alzheimer Disease.

Passive immunotherapy for Alzheimer disease has been tried for over 10 years without success. However, in 2021 and most recently in January 2023, the US Food and Drug Administration granted accelerated approval of 2 antibodies for this purpose, aducanumab and lecanemab. In both cases, the approval was based on a presumed therapy-related removal of amyloid deposits from the brain and, in the case of lecanemab, also some delay in cognitive decline. We question the validity of the evidence for the removal of amyloid in particular as assessed by amyloid PET imaging, believing that what is observed is more likely a large nonspecific amyloid PET signal in the white matter that diminishes during immunotherapy-in line with dose-dependent increases in amyloid-related imaging abnormalities and increased loss of cerebral volume in treated compared with placebo patients. To investigate this further, we recommend repeat FDG PET and MRI in all future immunotherapy trials.

Risk Factors for Various Cognitive Function Decline Trajectories in Adults Over 40 Years of Age: A Retrospective Cohort Study.

The aims of our study were to identify distinct trajectories of cognitive function using the group-based trajectory model. We also investigate which demographic factors act as risk factors for cognitive decline in each group. The data from the Seoul National University Hospital Healthcare System Gangnam Center, from 2005 to 2019. The number of study subjects was 637. We used a group-based model to identify cognitive function trajectories. Multinomial logistic regression was employed to define risk factors for cognitive function decline. The cognitive function trajectories among adults over 40 years of age were heterogeneous. We identified four trajectories: high (27.3%), medium (41.0%), low (22.7%), and rapid decline (9.1%). Older age, male, low educational level, bad dietary habits, diabetes mellitus, technical worker, and lower income increased the likelihood of a cognitive function decline. A younger age, a higher educational level, professional worker, good dietary habits, no diabetes mellitus, and no obesity improved cognitive function. A combination of these factors can improve "cognitive reserve" and delay cognitive decline. Interventions to prevent cognitive decline are needed after identification of high-risk groups for cognitive decline.

Effect of dietary supplementation with multinutrient soy flour on body composition and cognitive function in elderly individuals at the risk of low protein: a randomized, double-blind, placebo-controlled study.

Insufficient protein intake and cognitive decline are common in older adults; however, there have been few studies on low protein risk screening and complex nutrient interventions for elderly individuals in rural communities. This study aimed to evaluate the effect of dietary multinutrient soy flour (MNSF) on body composition and cognitive function in elderly individuals who are at risk of protein deficiency in a randomized, double-blind, placebo-controlled clinical trial. Nutritional interventions were given to those found to have low protein levels using bioelectrical impedance analysis (BIA). Among 733 older adults screened, 62 participants were included and randomly assigned into two groups, one taking soy flour and the other taking MNSF for 12 weeks. A previous cross-sectional survey found that 35.1% of the elderly people with an average age of 71.61 ± 5.94 years had an inadequate body protein mass proportion. After the intervention, the MNSF group demonstrated a significant improvement in protein mass, muscle mass, mineral levels, skeletal muscle mass, and fat-free mass compared with baseline (all P < 0.05), as well as a better upward trend compared with the soy flour group (P = 0.08; P = 0.07; P = 0.05; P = 0.08; P = 0.07). Regarding the mini-mental state examination (MMSE) scores, the MNSF group showed a significant decrease after 12 weeks (P < 0.05), which were significantly different compared with the soy flour group (P < 0.05). In the future, the application of MNSF as a food-based supplement to improve nutrition and delay cognitive decline in older adults at the risk of protein deficiency may be considered.

Protocol for a Mixed-Methods Process Evaluation of BetterBrains: A Person-Centered Online Intervention to Delay Cognitive Decline in Adults at Risk of Dementia.

The BetterBrains Randomized Controlled Trial (RCT) will evaluate the effectiveness of an online, person-centered, risk factor management, coaching intervention in community-dwelling, healthy adults at risk of cognitive decline. Multi-component interventions are challenging to evaluate due to program complexity and personalization to individual needs and contexts. This paper describes a multi-level process evaluation conducted alongside the BetterBrains RCT. To understand how and why the BetterBrains intervention was effective or ineffective at reducing cognitive decline in healthy adults whilst considering the context in which it was implemented. 1,510 non cognitively-deteriorated community-dwelling adults aged 40-70 years old at risk of cognitive decline will be recruited and randomly assigned to the intervention or control group. All BetterBrains intervention participants, coaches, and the research team will be included in the evaluation. A mixed-methods design will be used, guided by The Framework for Implementation Fidelity and the program logic model. Data will be sourced from interviews, focus groups, surveys, BetterBrains coach notes, participant weekly check-in surveys, and audio recordings of intervention coaching sessions. Quantitative data will be analyzed via descriptive and inferential statistics and qualitative data will be analyzed using content and thematic analysis. The process evaluation will provide information about contextual and influencing factors related to the implementation of BetterBrains and the RCT outcomes. Understanding how BetterBrains was implemented and its associated impacts will inform the translation of the program into community and clinical settings, providing easy access to online, personalized dementia prevention services.

PROPOSING THE NEUROGENESIS HYPOTHESIS FOR ALZHEIMER’S DISEASEWITH A CASE STUDY‐ PHASE 2 CLINICAL TRIALS OF NA‐831

AbstractBackgroundIn the hippocampus, new neurons are generated throughout life via a process called adult hippocampal neurogenesis (AHN). In mild cognitive impairment (MCI) and mild to moderate AD (early AD), AHN is reduced suggesting that AHN impairment compromises hippocampal functions. Augmenting AHN could help prevent or slow cognitive decline in MCI and early AD. The neurogenesis hypothesis is supported by the results of a Phase 2 randomized, double‐blind, placebo controlled clinical trial of NA‐831.MethodNA‐831 is a small drug molecule, which activates synaptic AMPA receptors, and increases the expression of brain derived neurotrophic factor (BDNF), which is crucial in synaptic plasticity, learning and memory formation in the hippocampus. NA‐831 restores neurogenesis by increasing the number of DCX+PCNA+ neuroblast cells. The study was conducted in 56 patients with MCI, mild and moderate Alzheimer’s disease, who received 10mg to 30 mg of NA‐831 or placebo orally per day for 24 weeks.ResultNA‐831 provided a significant delay in cognitive decline in MCI as measured by ADAS‐Cog‐13, an average score difference of 3.4 compared to placebo (p = 0.01; ITT) after 24 weeks of treatment. Similarly, NA‐831 delayed cognitive decline in early AD, an average score difference of 4.1 com‐pared to placebo (p = 0.001; ITT). CIBIC‐Plus showed 78% of the study participants receiving NA‐831 improved (p = 0.01; ITT). NA‐831 was well‐tolerated at 30 mg/day for 24 weeks, and no serious adverse events were observed.ConclusionThe Neurogenesis Hypothesis, and details of the Phase 2 clinical trials will be presented and discussed.

Investigating the protective contribution of PLCG2 P522R variant in microglia‐mediated immune pathways in Alzheimer’s Disease

AbstractBackgroundAs the main innate immune cell in central nervous system (CNS), microglia plays an indispensable roles in neuroinflammation and neurodegenerative diseases, such as Alzheimer’s Disease (AD). Large scale population studies have identified an AD‐associated rare coding variant in the Phospholipase C Gamma 2 (PLCG2) locus (rs72824905, P522R, P=5.38x10‐10, odds ratio = 0.68), which potentially offers protection against AD. This variant is associated with lower Aβ1‐42 and pTau181 levels in patients, as well as delays cognitive decline in mild cognitive impairment (MCI) progression. It has been reported that PLCG2 highly expresses in microglia in CNS and mainly involved in immune response, therefore, PLCG2 P522R variant may be a central player in the microglial‐mediated immune pathways during AD pathogenesis.MethodWe generated a PLCG2522R/R knock‐in mouse model carrying this human variant with CRISPR‐mediated gene editing. To explore the protective nature of PLCG2 P522R variant, we generated PLCG2522R/R; 5XFAD mouse model by crossing PLCG2522R/R knock‐in model with the 5XFAD mice, and accessed major AD phenotypes including Aβ load and microgliosis in vivo.ResultOur data showed that PLCG2522R/R;5XFAD mice exhibited attenuated AD pathologies compared with PLCG2522P/P;5XFAD mice, including less burden of Aβ in cortical and hippocampal regions, and less Aβ‐associated microglia clustering around Aβ plaques at early stage of AD.Conclusion PLCG2 P522R variant can protect against AD pathology in PLCG2522R/R;5XFAD mice, which may likely link to its hypermorphic effect in immune pathways, so that PLCG2522R/R microglia potentially have improved phagocytotic function and restrict Aβ accumulation in brain. We believe that investigating the protective role of PLCG2 P522R mutation may help us better understand the neuroinflammation aspect of AD pathogenesis, and provide new strategies to developing clinical therapy in the future.

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

Effect of cognitive rehabilitation training combined with butylphthalide soft capsules and ginkgo-leaf tablets on patients with mild Alzheimer's disease

Purpose: To study the impact of a combination of cognitive rehabilitation training, butylphthalide soft capsules and ginkgo-leaf tablets on patients with mild Alzheimer’s disease (AD).Methods: One hundred and twenty-eight (128) mild AD patients were randomly assigned to medication treatment group (MT group, n = 64) and joint training group (JT group, n = 64). Both groups were treated with butylphthalide soft capsules and ginkgo-leaf tablets, while the JT group additionally received cognitive rehabilitation training. Therapeutic effects and adverse drug reactionsin the two groups were assessed.Results: Total effectiveness was significantly higher in JT patients (84.38 %) than in MT patients (60.94 %; χ2 = 8.9320). After treatment, Mini-Mental State Exam (MMSE), Activity of Daily Living (ADL) and ADAS-cog scores in the JT group were significantly better than those in the MT group, (p &lt; 0.05). There were significantly lower plasma NO, serum VEGF and MDA levels in JT patients than in MT patients. CRP and Hcy levels were markedly lower in JT than in MT patients. The incidence of adverse reactions in both groups was comparable (p &gt; 0.05).Conclusion: Rehabilitation training in combination with butylphthalide soft capsule and ginkgo-leaf tablets produce significant therapeutic impact on mild AD patients. The combination therapy delays cognitive decline and memory loss in AD patients, improves their serological indicators, and lowers the incidence of adverse reactions.

Multimodal strategy to rescue the brain in mild cognitive impairment: Ketogenic oral nutrition supplementation with B vitamins and aerobic exercise

Mild cognitive impairment (MCI) is characterized by a decline in cognition and is associated with a higher risk of progression to dementia and Alzheimer's disease (AD). Considering the complexity and multifactorial etiology of MCI, dementia, and AD, there is a growing understanding that optimal preventive strategies are likely to require targeting several risk factors and mechanisms simultaneously. Recent evidence shows that interventions such as exercise, in particular aerobic exercise (AE), exogenous sources of ketones (namely ketogenic medium-chain triglyceride [kMCT]), and supplementation with vitamins B12 , B6 and folic acid may positively impact cognitive performance in MCI and AD. Although further studies might be necessary to understand the exact pathways through which this occurs, there are reasons to suspect that, in combination, these interventions could have a synergetic effect. In this paper, we hypothesize that a multicomponent cognitive therapy with ketogenic oral nutritional supplementation with vitamins B12 , B6 , and folic acid, and AE could have a synergistic effect and help delay cognitive decline in patients with MCI. Further studies that include objective measurements of cognitive function are needed to confirm this hypothesis.

Are clinical trials randomising households to lifestyle interventions to delay cognitive decline feasible? A pilot study to determine the beliefs, preferences, and deterrents for households impacted by dementia based on semi-structured interviews

IntroductionWhile lifestyle risk factors are implicated in the development and progression of cognitive impairment, interventional trials of individual participants have yielded unconvincing evidence. We sought to explore the development of lifestyle interventions targeting the household-unit.MethodsSemi-structured interviews were carried out among eight households affected by cognitive impairment (i.e. member of the household had cognitive impairment). Interviews took place online using a secure, web-based video platform recommended for patient clinician interaction. Interview content was analysed, and important themes identified.ResultsEighteen participants were interviewed within households, of which eight (one per household) had cognitive impairment and others were spouses or first-degree relatives living in the same home. Several themes emerged; 1) household members without cognitive impairment were more likely to report poor sleep habits, and sleep was perceived to be the hardest behaviour to change; 2) diet generated most interest as a potential lifestyle intervention target as most participants believed there is a strong link with nutrition and cognition; 3) physical activity is challenging to adapt due to lack of motivation and focus when individuals are cognitively impaired. Barriers to study participation, including risk of harm, complexity of intervention and deviation from routine emerged during discussions.ConclusionsThis study identified beliefs and preferences of households towards lifestyle intervention trials. Findings from this study may be used to inform future clinical trial protocols and future qualitative studies should explore acceptability and feasibility of digital intervention applications.

Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial

ObjectivesWe aimed to examine the effects of multisite anodal transcranial direct current stimulation (tDCS) combined with cognitive stimulation (CS) over 2 months on cognitive performance and brain activity, and the relationship between them, in patients with Alzheimer's disease (AD). MethodsPatients with AD were randomly assigned to an active tDCS+CS (n=18) or a sham tDCS+CS (n=18) group. Cognitive performance was assessed using the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain activity using EEG (spectral power and coherence analysis) before and after the intervention. Multisite anodal tDCS (2 mA, 30 min) was applied over six brain regions [left and right dorsolateral prefrontal cortex (F3 and F4), Broca's area (F5), Wernicke's area (CP5), left and right somatosensory association cortex (P3 and P4)] for 24 sessions (three times a week). Both groups performed CS during tDCS. ResultsAnodal tDCS+CS delays cognitive decline (ADAS-cog change) to a greater extent than sham tDCS+CS (-3.4±1.1 vs. -1.7±0.4; p=.03). Bilateral EEG coherence at high and low frequencies was greater for the active tDCS+CS than sham+CS group for most electrode pairs assessed (p < .05). The post-intervention ADAS-cog change score was predictive for EEG coherence at different sites (R²=.59 to .68; p < .05) in the active but not in the sham tDCS+CS group. ConclusionAnodal tDCS+CS improved overall cognitive function and changed EEG brain activity compared to sham tDCS+CS. Changes in cognitive performance were associated with changes in EEG measures of brain activity. Anodal tDCS+CS appears to be a promising therapeutic strategy to modulate cortical activity and improve cognitive function in patients with AD.

Plasma Aβ1–42 dominantly predicts cognitive decline

AbstractBackgroundIn populations at‐risk for developing dementia, such as patients with Down’s syndrome, stroke, and amnestic mild cognitive impairment, it is important to be able to predict the progression to dementia or cognitive decline. is important to be able to predict the progression to dementia or cognitive decline. In clinical practice, a convenient examination that can evaluate the progression to dementia or cognitive decline is urgently needed.MethodNotably, there are limitations in this work. Only five studies are available for this review because such studies are novel.ResultAccording to this review, plasma Aβ1‐42 possibly plays a more key role in this prediction than Aβ1‐40 or Tau. This implies that abnormal levels of Aβ1‐42 might possibly be a critical trigger of the onset of developing dementia or cognitive decline.ConclusionIt would be hopeful to stop the development of dementia or delay cognitive decline by eliminating the abnormal changes in the level of plasma Aβ1‐42.