Prodromal Stage Of Dementia Research Articles

Effects of fully immersive virtual reality training on cognitive function in patients with mild cognitive impairment: a systematic review and meta-analysis

BackgroundMild cognitive impairment (MCI) is a prodromal stage of dementia. There is no specific medication to slow the progression of MCI. Recent studies have confirmed the positive effects of virtual reality (VR). However, the results are inconsistent due to different types of VR interventions, small sample sizes, and the varying quality of the literature. This study aimed to assess the effects of fully immersive VR on cognitive function in MCI patients.MethodsA systematic review of published literature was conducted using PubMed, Cochrane Library, Embase, CINAHL, Web of Science, SinoMed, CNKI, Wanfang, and VIP Database. The search period was from inception through March 1, 2024. Eligible studies were randomized controlled trials evaluating the effects of fully immersive virtual reality training on cognitive function in MCI patients. Two investigators independently performed literature screening, data extraction, and quality assessment; a meta-analysis of the included literature was performed using RevMan 5.4. The Cochrane Risk of Bias tool was used to assess the methodological quality.ResultsA total of 11 randomized controlled trials with 525 patients were included. The meta-analysis showed that fully immersive virtual reality training had significant effects on global cognitive function (MD = 2.34, 95% CI [0.55, 4.12], p = 0.01); (MD = 0.93, 95% CI [0.30, 1.56], p < 0.01), executive function (SMD = -0.60, 95% CI [−0.84, −0.35], p < 0.01), and attention (MD = 0.69, 95% CI [0.15, 1.23], p = 0.01). Still, the difference in memory (SMD = 0.27, 95% CI [−0.24, 0.78], p = 0.30) was not statistically significant. Subgroup analyses showed that executive function could be improved only when the intervention duration was ≥40 h. In contrast, excessive training (≥30 times) was counterproductive.ConclusionFully immersive virtual reality training improved cognitive functioning, executive functioning, and attention in MCI patients but was less effective in improving memory. Subgroup analysis suggests that fully immersive VR training must ensure sufficient intervention duration while avoiding frequent interventions.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42024498629).

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty, characterized by the coexistence of cognitive impairment and physical frailty, represents a multifaceted challenge in the aging population. The role of cardiovascular risk factors in this complex interplay is not yet fully understood. AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia. METHODS A comprehensive approach was employed, with a total of 512 community-dwelling older persons aged 60 years and above, involving two cohorts of older persons from previous studies. Datasets related to cardiovascular risks, namely sociodemographic factors, and cardiovascular risk factors, including hypertension, diabetes, hypercholesterolemia, anthropometric characteristics and biochemical profiles, were pooled for analysis. Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score. Cardiovascular risk was determined using Framingham risk score. Statistical analyses were conducted using SPSS version 21. RESULTS Of the study participants, 46.3% exhibited cognitive frailty. Cardiovascular risk factors including hypertension (OR:1.60; 95%CI: 1.12-2.30), low fat-free mass (OR:0.96; 95%CI: 0.94-0.98), high percentage body fat (OR:1.04; 95%CI: 1.02-1.06), high waist circumference (OR:1.02; 95%CI: 1.01-1.04), high fasting blood glucose (OR:1.64; 95%CI: 1.11-2.43), high Framingham risk score (OR:1.65; 95%CI: 1.17-2.31), together with sociodemographic factors, i.e. , being single (OR 3.38; 95%CI: 2.26-5.05) and low household income (OR 2.18; 95%CI: 1.44-3.30) were found to be associated with cognitive frailty. CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty, a prodromal stage of dementia. Early identification and management of cardiovascular risk factors, particularly among specific group of the population might mitigate the risk of cognitive frailty, hence preventing dementia.

Non-linear relationship between serum cholesterol levels and cognitive change among older people in the preclinical and prodromal stages of dementia: a retrospective longitudinal study in Taiwan

BackgroundAdverse effects of rigorously lowering low-density lipoprotein cholesterol on cognition have been reported; therefore, we aimed to study the contribution of serum cholesterol in cognitive decline in older people with or without dementia.MethodsCognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI). We investigated associations between serum cholesterol with cognitive decline using multiple regressions controlling for the effects of demographics, vascular risk factors, and treatments.ResultsMost associations between cholesterol and CASI scores could be explained by non-linear and inverted U-shaped relationships (R2 = 0.003–0.006, p < 0.016, Šidákcorrection). The relationships were most evident between changes in cholesterol and CASI scores in older people at the preclinical or prodromal stages of dementia (R2 = 0.02–0.064, p values < 0.016). There were no differences in level of changes in CASI scores between individuals in 1st decile and 10th decile groups of changes in cholesterol (p = 0.266–0.972). However, individuals in the 1st decile of triglyceride changes and with stable and normal cognitive functions showed significant improvement in CASI scores compared to those in the 10th decile (t(202) = 2.275, p values < 0.05).ConclusionThese findings could implicate that rigorously lowering cholesterol may not be suitable for the prevention of cognitive decline among older people, especially among individuals in preclinical or prodromal stages of dementia.

N-3 Polyunsaturated Fatty Acids in Elderly with Mild Cognitive Impairment: A Systemic Review and Meta-Analysis.

Mild cognitive impairment (MCI) is the prodromal stage of dementia. In this stage, reasonable intervention measures can help to delay the decline of cognitive function. Supplementation of n-3 polyunsaturated fatty acids (n-3PUFAs) may be beneficial to delay the decline of cognitive function in the elderly. To investigate the effectiveness of docosapentaenoic acid (DHA) or/and eicosapentaenoic acid (EPA) supplements in the elderly with MCI. Eight electronic databases, PubMed, Cochrane Library, Embase, VIP, SinoMed, Web of Science, CNKI, and WANFANG DATA, were searched for related articles from inception until January 2022. Subgroup analyses and sensitivity analyses were performed to detect confounding variables. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots. Stata12.0 was used for Begg's and Egger's test to quantify whether publication bias. Linear relationship between global cognition and covariates was examined in meta-regression analysis. Twelve studies (n = 1,124) were included. The methodological quality of research is mostly medium. Compared with placebo, n-3PUFAs supplements have benefits on global cognition [SMD = 0.51, 95% CI(0.12, 0.91), p = 0.01]. No significant differences were observed between intervention group and placebo on language fluency, executive functions, and depression. Our findings indicated DHA and/or EPA supplements have benefits on global cognition, and it may also reduce the level of blood amyloid-β (Aβ)-related biomarkers (e.g., Aβ40, Aβ42) and inflammatory factors (e.g., 1L-6, 1L-10). Since there are only two relative articles, more research is needed in the future to clarify the relationship.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Cognitive, Emotional, and Daily Functioning Domains Involved in Decision-Making among Patients with Mild Cognitive Impairment: A Systematic Review.

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive-emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients' daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individuals.

Association of mobile device proficiency and subjective cognitive complaints with financial management ability among community-dwelling older adults: a population-based cross-sectional study

BackgroundMobile devices have been used by many older adults and have the potential to assist individuals with subjective cognitive complaints (SCCs) in daily living tasks. Financial management is one of the most complex daily activity for older adults, as it is easily impaired in the prodromal stage of dementia and cognitive impairment.AimTo investigate financial management ability among older adults from SCCs and mobile device proficiency.MethodsA self-administered questionnaire was sent to 529 participants who were ≥ 65 years and regularly use mobile devices. Participants were divided into four groups based on SCC prevalence and scores of the Mobile Device Proficiency Questionnaire (MDPQ-16). Financial management abilities were compared between groups using the Process Analysis of Daily Activities for Dementia subscale. Regression model and crosstabulation table were used to investigate associations in detail.ResultsA significant difference in financial management ability was observed among the four groups (p < 0.001), with the dual impairment group showed significantly lower than the robust and SCC groups (p < 0.001). Educational history, sex, and MDPQ-16 score were significantly associated with participants’ financial management ability (p ≤ 0.01). The proportion of participants who could use ATMs and electronic money independently was significantly lower among those with low proficiency in mobile devices (LPM), regardless of SCC (p < 0.05).ConclusionThe LPM group showed an impaired ability to manage their finances, particularly in situations where they would use information devices. Therefore, healthcare professionals should assess not only the SCC but also their proficiency with mobile devices to predict their impairment in activities of daily living.

Electrical field strength from anodal prefrontal tDCS determines degree of white matter integrity changes in amnestic MCI patients

AbstractBackgroundAn electrical field (EF) strength induced by tDCS affects a therapeutic effect. Additionally, sequential tDCS has improved white matter integrity in cognitively impaired patients. However, researchers have not evaluated the impact of EF strength on white matter integrity in the prodromal stage of dementia. This study aimed to elucidate the effect of EF strength from prefrontal anodal tDCS on white matter integrity change and the modulating role of relevant genetic and pathologic factors in this effect in amnestic mild cognitive impairment (MCI) patients.MethodIn 55 amnestic MCI patients, we delivered anodal‐tDCS (2 mA/day, five times/week, for two weeks) over the left dorsolateral prefrontal cortex (DLPFC), calculated the EF strength for the left inferior frontal gyrus and DLPFC through the stimulation navigation program analysis. Additionally, we assessed the white matter integrity by diffusion tensor imaging before and after two weeks of stimulation; finally, we evaluated the modulating factors: amyloid‐beta (Aβ) deposition, APOE ε4‐allele status, and BDNF polymorphism.ResultAs the EF intensity in the left inferior frontal gyrus increased, the range of changes in white matter integrity significantly increased in left anterior thalamic radiation, corticospinal tract, inferior fronto‐occipital fasciculus, and inferior longitudinal fasciculus. Additionally, we found that greater change in white matter integrity was observed with higher regional EF strength in the APOE ε4 non‐carriers and BDNF MET non‐carrier, which could be attributed to an interaction between these modulating factors and EF intensity in the left anterior thalamic radiation and right uncinate fasciculus.ConclusionThese findings provide evidence for the precision‐medicine‐based application of tDCS in the prodromal stage of dementia, inducing the optimized therapeutic effect.

Neuropathological correlates of neuropsychiatric symptoms in the Brains for Dementia Research study

AbstractBackgroundNeuropsychiatric symptoms are a common feature of many dementia syndromes, and are frequently associated with poor clinical prognosis, reduction in quality of life, earlier institutionalisation, greater disability, and increased caregiver distress, particularly during later stages of disease. It has also been postulated that NPS may occur during prodromal stages of dementia, preceding or alongside early cognitive symptoms. Clinical profiles of dementia are both heterogenous and intersecting, which may reflect that up to 90% of cases have multiple pathologies post‐mortem. Comprehensive clinicopathological studies of neuropsychiatric symptoms in dementia are lacking, thus this study sought to investigate potential neuropsychiatric profiles resulting from mixed underlying pathology.MethodThis analysis aimed to identify pathological correlations of neuropsychiatric symptoms and included 840 post‐mortem brains donated to the Brains for Dementia Research project, a longitudinal study with post‐mortem neuropathological assessment across several brain banks, between 2008 and 2020. Patterns of neuropsychiatric symptoms were compared between pathology subtypes using clinical data including the Neuropsychiatric Inventory (NPI‐Q) and Clinical Dementia Rating scale, and neuropathological assessment of degenerative pathologies and vascular features. Confirmatory factor analysis was used to identify latent variables for psychosis, mood, and behaviour. Associations between pathological variables assessed at autopsy and neuropsychiatric features during life were explored using bivariate and multivariate statistical methods.ResultAlmost 80% of the 494 dementia cases included had at least one neuropsychiatric symptom across the course of disease. Apathy (51.2%) and aggression (41.7%) were the most prevalent neuropsychiatric features across all dementia subtypes. Preliminary results indicate that different underlying pathologies, including neurodegenerative pathologies (amyloid, neurofibrillary tangles, Lewy bodies, TDP‐43 inclusions) and vascular features may be associated with increased likelihood of specific neuropsychiatric symptoms, such as psychosis, mood and behaviour, during life. Co‐occurring substantial AD and Lewy body pathology was associated with the presence of anxiety, depression, and aberrant motor activity during life. AD in the absence of substantial Lewy body pathology, was associated with agitation, apathy, and disinhibition. Lewy body pathology, in the absence of substantial AD pathology, was associated with hallucinations, depression and sleep disturbances.ConclusionThe interaction of multiple pathologies may contribute to differing neuropsychiatric profiles during life.

A narrative review on mild behavioural impairment: an exploration into its scientific perspectives.

In clinical practice, the admission of patients with late-onset psychological and behavioural symptoms is frequent, regardless of the presence or absence of cognitive decline. These symptoms commonly occur in the prodromal stage of dementia and can precede the onset of dementia. While the concept of Mild Cognitive Impairment (MCI) -which is defined as a level of cognitive impairment insufficient to impact daily functioning- is well established, the notion of Mild Behavioural Impairment (MBI) is not yet widely recognized. However, studies have demonstrated that the presence of MBI in both cognitively normal patients and individuals with MCI is associated with an increased risk of dementia progression. Thus, MBI may serve as a neurobehavioral indicator of pre-dementia risk states. This narrative review aims to discuss the evolution of the term, the relevant clinical aspects, and potential biomarkers that may contribute to the clinical definition of MBI. The objective is to assist clinicians in recognizing the diagnosis and differentiating it from psychiatric syndromes, as well as identifying possible etiologies of neurodegeneration.

APOE4 and confluent WMH have a synergistic effect on episodic memory impairment in prodromal dementia

AbstractBackgroundWhite matter hyperintensities (WMH) are a known risk factor for cognitive decline (C.Puzo el. al. 2019). While the ε4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline in concomitance with WMH (D.Tsuang et. al. 2013), it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia. Our objective was thus to determine how APOE4 moderates the relationship between WMH and cognition in prodromal dementia.Method216 participants with prodromal dementia underwent magnetic resonance imaging (MRI), neuropsychological testing (global and domain‐specific), cardiovascular risk factor assessments and APOE genotyping. Visual ratings for WMH as well as total and lobar WMH volumes were quantified. Moderation analysis was performed to determine the influence of APOE4 on the relationship between WMH and performance on global and domain‐specific cognitive measures (executive function, episodic memory, attention, language) in moderation analysis (Figure 1). The role of confluent and non‐confluent WMH subtype on cognition was additionally studied using moderation analysis and logistic regression (Figure 1).ResultAPOE4 carriers (n = 49) had poorer memory and higher global WMH (p = 0.04), temporal WMH (p = 0.01) and occipital WMH (p = 0.02) compared to APOE4 non‐carriers (n = 167). APOE4 strengthened the relationship between higher total WMH burden and worse episodic memory performance (Fig.2a). At the lobar WMH level, APOE4 strengthened associations between frontal, temporal, parietal and occipital WMH and episodic memory performance (Fig.2b, Fig.2c, Fig.2d, and Fig.2e) with large sized effects (β). APOE4 did not interact with either total or lobar WMH to predict worse cognition in other cognitive domains. Moreover, APOE4 strengthened the relationship between frontal WMH with episodic memory in the confluent WMH subgroup (Fig.2f). Logistic regression model showed memory impairment was 4.81 times more likely to develop in patients carrying APOE4 and with confluent WMH compared to APOE4 non‐carriers and those with non‐confluent WMH (OR 4.81, β 1.57, p&lt;0.01).ConclusionThe impact of WMH on memory may be strongest in APOE4 carriers at the prodromal dementia stage. Clinicians targeting WMH would need to consider the APOE4 allele and WMH severity status to strategize cognitive interventions.

An Exploratory Study of Sleep-Wake Differences of Autonomic Activity in Patients with Mild Cognitive Impairment: The Role of Melatonin as a Modulating Factor.

The objective of the present study was to assess sleep-wake differences of autonomic activity in patients with mild cognitive impairment (MCI) compared to control subjects. As a post-hoc objective, we sought to evaluate the mediating effect of melatonin on this association. A total of 22 MCI patients (13 under melatonin treatment) and 12 control subjects were included in this study. Sleep-wake periods were identified by actigraphy and 24hr-heart rate variability measures were obtained to study sleep-wake autonomic activity. MCI patients did not show any significant differences in sleep-wake autonomic activity when compared to control subjects. Post-hoc analyses revealed that MCI patients not taking melatonin displayed lower parasympathetic sleep-wake amplitude than controls not taking melatonin (RMSSD -7 ± 1 vs 4 ± 4, p = 0.004). In addition, we observed that melatonin treatment was associated with greater parasympathetic activity during sleep (VLF 15.5 ± 0.1 vs 15.1 ± 0.1, p = 0.010) and in sleep-wake differences in MCI patients (VLF 0.5 ± 0.1 vs 0.2 ± 0.0, p = 0.004). These preliminary findings hint at a possible sleep-related parasympathetic vulnerability in patients at prodromal stages of dementia as well as a potential protective effect of exogenous melatonin in this population.

New Insights into Potential Biomarkers in Patients with Mild Cognitive Impairment Occurring in the Prodromal Stage of Dementia with Lewy Bodies

Prodromal dementia with Lewy bodies (DLB) can emerge with the onset of mild cognitive impairment (MCI). Standard biomarkers can help identify such patients to improve therapy and treatment strategies. Our review aims to describe the latest evidence on promising biomarkers in prodromal DLB with MCI onset (MCI-LB). We selected articles on different biomarkers in MCI-LB from PubMed and conducted a narrative review. We identified potentially promising clinical biomarkers, e.g., (1) assessing autonomic symptoms specifically, (2) describing the cognitive profile in several subdomains including executive and visual functions, and (3) measuring the speed of speech. In addition, we describe the measurement of seeding amplification assays of alpha-synuclein in cerebrospinal fluid as a relevant biomarker for MCI-LB. Electroencephalographic markers, as in calculating the theta/beta ratio or intermittent delta activity, or analyzing peak frequency in electroencephalography-methods also potentially useful once they have been validated in large patient cohorts. The 18F fluorodesoxyglucose positron emission tomography (FDG-PET) technique is also discussed to investigate metabolic signatures, as well as a specific magnetic resonance imaging (MRI) technique such as for the volumetric region of interest analysis. These biomarker results suggest that MCI-LB is a promising field for the use of biomarkers other than established ones to diagnose early prodromal DLB. Further large-scale studies are needed to better evaluate and subsequently use these promising biomarkers in prodromal DLB.

Altered Feedback-Related Negativity in Mild Cognitive Impairment

Feedback-related negativity (FRN) is electrical brain activity related to the function of monitoring behavior and its outcome. FRN is generated by negative feedback input, such as punishment or monetary loss, and its potential is distributed maximally over the frontal-central part of the skull. Our previous study demonstrated that FRN latency was delayed and that the amplitude was increased in patients with mild Alzheimer's disease (AD). As mild cognitive impairment (MCI) is considered to be a prodromal stage of AD, we speculated that FRN would also be altered in MCI, as in AD. The aim of this study is to examine whether MCI patients showed changes in FRN during a gambling task. Thirteen MCI patients and thirteen age-matched healthy elderly individuals participated in a simple gambling task and underwent neuro-psychological assessments. The participants were asked to choose one out of two options and randomly received positive or negative feedback to their response. An EEG was recorded during the task, and FRN was obtained by subtracting the positive feedback-related activity from the negative feedback-related activity. The reaction time to probe stimuli was comparable in the two groups. The group comparisons revealed that the FRN amplitude was significantly larger for the MCI group than for the healthy elderly (F(1,24) = 6.4, ηp2 = 0.22, p = 0.019), but there was no group difference in the FRN latency. The FRN amplitude at the frontocentral electrode positively correlated with the mini-mental state examination score (Spearman's rhopartial = 0.41, p = 0.043). The finding of increased FRN amplitude in MCI was consistent with the previous finding in AD. Our findings indicate that monitoring dysfunction might also be involved in the prodromal stage of dementia.

Diagnostic Performance of a Tablet Computer-Based Cognitive Screening Test for Identification of Amnestic Mild Cognitive Impairment.

Early and appropriate diagnosis of amnestic mild cognitive impairment (aMCI) is clinically important because aMCI is considered the prodromal stage of dementia caused by Alzheimer's disease (AD). aMCI is assessed using the comprehensive neuropsychological (NP) battery, but it is rater-dependent and does not provide quick results. Thus, we investigated the performance of the computerized cognitive screening test (Inbrain Cognitive Screening Test; Inbrain CST) in the diagnosis of aMCI and compared its performance to that of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test (CERAD-K), a comprehensive and pencil-and-paper NP test. A total of 166 participants were included in this cross-sectional study. The participants were recruited as part of a prospective, community-based cohort study for MCI (PREcision medicine platform for mild cognitive impairment on multi-omics, imaging, evidence-based R&amp;BD; PREMIER). All participants were assessed using the CERAD-K and the Inbrain CST. The Inbrain CST comprised seven subtests that assessed the following five cognitive domains: attention, language, visuospatial, memory, and executive functions. Seventy-six participants underwent brain magnetic resonance imaging and [18F]-flutemetamol positron emission tomography (PET). We evaluated the diagnostic performance of the Inbrain CST for the identification of aMCI by comparing the findings with those of CERAD-K. We also determined the characteristics of aMCI patients as defined by the CERAD-K and Inbrain CST. Of the 166 participants, 93 were diagnosed with aMCI, while 73 were cognitively unimpaired. The sensitivity of the Inbrain CST for aMCI diagnosis was 81.7%, and its specificity was 84.9%. Positive and negative predictive values were 87.4% and 78.5%, respectively. The diagnostic accuracy was 83.1%, and the error rate was 16.9%. Demographic and clinical characteristics between individuals with aMCI defined by the Inbrain CST and CERAD-K were not significantly different. The frequency of positive amyloid PET scan, the hippocampal/parahippocampal volumes, and AD signature cortical thickness did not differ between the patients with aMCI defined by CERAD-K and those with aMCI defined by the Inbrain CST. The Inbrain CST showed sufficient sensitivity, specificity, and positive and negative predictive values for diagnosing objective memory impairment in aMCI. In addition, aMCI patients identified by CERAD-K and the Inbrain CST showed comparable clinical and neuroimaging characteristics. Therefore, the Inbrain CST can be considered an alternative test to supplement the limitations of existing pencil-and-paper NP tests.

How does a diagnosis of mild cognitive impairment impact everyday behaviours, quality of life and healthcare utilisation? A systematic review of people with MCI and their carers.

AbstractBackgroundThe UK National Dementia Strategy was developed to improve professional and public attitudes and understanding around dementia, and to ensure through all stages of dementia that patients receive high‐quality care and support(1). Mild cognitive impairment (MCI) is a prodromal stage of dementia that can impact on patients’ everyday behaviours and quality of life (QOL). Carers may undertake additional responsibilities, which may ultimately impact on their health. We conducted a systematic review on the impact of an MCI diagnosis on the lives of both the individual and carers/families, focusing on everyday behaviours, QOL, and healthcare utilisation.MethodThis systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews (PRISMA) checklist. We searched five large databases including Web of Science, Scopus, Medline, Embase and Psychinfo for studies published after Jan 2004, using appropriate key terms. Titles, abstracts and full texts were screened against set inclusion criteria. Data were extracted onto a customized data extraction sheet, and a narrative synthesis of all eligible studies was undertaken. This review was registered with PROSPERO (no CRD42021291995).ResultsTen papers were included. Patients diagnosed with MCI and cares/families described a lack of understanding of the term MCI itself, particularly around ‘mild’ and the anxiety around further cognitive decline. There was a perceived lack of information provided to both patient and carers around the diagnosis, with carers not perceiving themselves as carers up until that point. Carers also reported increased levels of depression and distress as they undertook more caring responsibilities. Carers experienced frustration with loved ones, who denied that they had memory problems and took longer to process and do things; this led to increased family conflict.ConclusionThis review identified the functional and psychosocial impact of a MCI diagnosis on people and carers. There is a critical need to combat stigma, increase information and support for people with MCI, and provide psychosocial interventions for people and carers post MCI diagnosis to enhance them to better cope and potentially reduce related depression, anxiety, and carer burden.1 Banerjee S. Living well with dementia–development of the national dementia strategy for England. Int J Geriatr Psychiatry. 2010;25:917‐922.

Comparison of the effect of computerized multidomain cognitive training and pen‐and‐paper educational program in older adults with mild cognitive impairment: a preliminary randomized controlled trial

AbstractBackgroundCognitive intervention is accepted as a potential therapy to prevent the incident dementia. It was found that computerized cognitive training might be effective for older adults with mild cognitive impairment (MCI) in previous studies. We aimed to find the effect of multidomain cognitive training using tablet computer on the cognitive and psychological function in patients with MCI.MethodParticipants in training group (n = 15) conducted a multidomain cognitive training program using table computer and those in control group (n = 13) conducted an educational book reading twice a week for eight weeks. They were evaluated of their cognitive and psychiatric function before and after the program. The differences of the pre‐ and post‐ scores were compared between training and control groups.ResultParticipants in training group showed improvement in cognitive domains such as language (p = 0.012), memory (p = 0.050), and frontal executive function (p = 0.017), and psychiatric symptoms such as apathy (p = 0.001) and quality of life (p = 0.035) after the training. Control group participants showed improvements in frontal executive function (p = 0.013), positive affect (p = 0.019), apathy (p = 0.022) and mild behavioral impairment score (p = 0.049). Between group comparison of the pre‐ and post‐training difference showed significant improvement in training group compared to control group in memory (p = 0.020), frontal executive function (p = 0.024), positive affect (p = 0.037), apathy (p = 0.048), and quality of life (p = 0.047).ConclusionWe found the effect of multidomain cognitive training using tablet computer in cognitive domain including memory and executive function, positive affect, apathy, and quality of life in MCI patients. Tablet computer cognitive training may be effective in multidomain cognitive training with transfer effect in the prodromal stage of dementia. Future trials with larger sample size and various devices would find the effect of the computerized cognitive training.

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the “what,” “for whom,” and “how” of exercise to promote cognitive function

BackgroundTargeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms.MethodsTwo hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer’s Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up).DiscussionEstablishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as “medicine” to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health.Trial registrationClinicalTrials.gov NCT02737878. Registered on April 14, 2016.

The relationship between uric acid and brain health from observational studies.

This study conducts a systematic literature review and meta-analysis regarding the potential influence of serum uric acid levels on cerebral small vessel diseases and the cognitive status in the prodromal stages of dementia. We identified four different cerebral small vessel diseases and three specific domains of cognitive performance to be considered in the literature search. The analysis contained 14 studies (13 cross-sectional design and one longitudinal design) with 11,502 participants measuring the relationship between uric acid and cerebral small vessel disease. In both continuous and categorical analyses, significant associations were found between hyperuricemia and cerebral small vessel diseases (continuous data: pooled OR: 1.00, 95%CI: 1.00-1.01 and categorical data: pooled OR: 1.42, 95%CI: 1.15-1.75). For the relationship between uric acid and cognitive performance, 19 studies with 49,901 participants were considered, including eight cohort studies, and 11 cross-sectional studies. The cross-sectional data showed that a marginal relationship existed between uric acid and global cognition (β: 0.00, 95%CI: -0.01-0.00). The pooled analysis of cohort studies indicated that higher uric acid had a deleterious effect on attention and executive function (continuous data: β: -0.02, 95%CI: -0.04-0.00 and categorical data: β: -0.03, 95%CI: -0.07-0.00). Conclusion: Our study indicated that a higher level of uric acid had an adverse effect on brain health. Furthermore, a high level of uric acid is related to cognitive decline in attention and executive function, which may exist a long time before the diagnosis of dementia.