Mild Cognitive Impairment Research Articles

Disgust-specific impairment of facial emotion recognition in Parkinson's disease patients with mild cognitive impairment.

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing "disgust," compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and "disgust" FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing "disgust" and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions.

Behavioral and Psychological Symptoms of Dementia and Mortality Risk Among People With Cognitive Impairment: An 8-year Longitudinal Study From the NCGG-STORIES.

Behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia from the early stages and can appear even in mild cognitive impairment (MCI). However, the prognostic impact of BPSD is unclear. This study examined the association between BPSD and mortality among people with cognitive impairment. This longitudinal study involved 1,065 males and 1,681 females (mean age: 77.1 years for males and 78.6 years for females) with MCI or dementia diagnosis from the National Center for Geriatrics and Gerontology-Life Stories of People with Dementia (NCGG-STORIES), a single-center memory clinic-based cohort study in Japan that registered first-time outpatients from 2010-2018. Information about death was collected through a mail survey returned by participants or their close relatives, with an up to 8-year follow-up. BPSD was assessed using the Dementia Behavior Disturbance Scale (DBD) at baseline. During the follow-up period, 229 (28.1%) male and 254 (15.1%) female deaths occurred. Cox proportional hazards regression analysis showed that higher DBD scores were significantly associated with increased mortality risk among males, but not females (compared with the lowest quartile score group, hazard ratios for the highest quartile score group were 1.59; 95% confidence interval, [CI] 1.11-2.29 for males and 1.06; 95% CI, 0.66-1.70 for females). Among the DBD items, lack of interest in daily living, excessive daytime sleep, and refusal to receive care had a higher mortality risk. The findings suggest a potential association between BPSD and poor prognosis among males with cognitive impairment.

Association of cognitive performance with overall, dosage, intensity, and domain physical activity in aging: NHANES 2011–2014

BackgroundThe specific relationship between PA in detailed types and cognition is still unclear due to limited evidence. Our study aimed to investigate the relationship between cognitive performance and various aspects of physical activity, including overall activity, dosage, intensity levels [moderate physical activity (MPA), vigorous PA], and different domains of activity [occupational PA (OPA), transportation PA (TPA), and leisure-time PA (LTPA)] in older adults using data from the NHANES database.MethodsThis cross-sectional analysis used data from 2 cycles of NHANES (2011–2014). PA was determined through participants' self-reports using the Global Physical Activity Questionnaire (GPAQ). Cognitive performance was evaluated by the presence of psychometric mild cognitive impairment (p-MCI), identified based on a composite measure derived from three cognitive tests including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency test, and the Digit Symbol Substitution test (DSST). Logistic regression models were used to evaluate the association.ResultsA total of 2588 participants aged 60 years or older were included, with an average age of 69.4 years and 48% being male. In the fully adjusted model, compared to no PA, performing 300 min of PA, and MPA were associated with 44%, and 33% reductions in the prevalence of p-MCI, respectively. Additionally, engaging in 1–149 min/week [OR 0.56, 95% CI (0.33–0.92)] and ≥ 300 min/week [OR 0.66, 95% CI (0.44–0.96)] of OPA, as well as ≥ 300 min/week [OR 0.56, 95% CI (0.36–0.86)] of LTPA, were also associated with a lower prevalence of p-MCI. Additionally, engaging in a diverse range of PA had better outcomes.ConclusionsOur results suggested a positive association between higher levels of PA and enhanced cognitive performance. Different intensities and domains of PA have varying impacts on cognition. Future exploration, such as objectively measured PA and longitudinal studies were needed to validate our conclusion.

Can Phonemic Verbal Fluency Be Used to Predict Alzheimer’s Disease?

Background: Among the cognitive markers, the deterioration of semantic and phonemic verbal fluency seems to be an early indicator of Alzheimer’s disease (AD). The aims of this study are (1) to evaluate both types of verbal fluency in the early stages of AD in order to know which of them deteriorates earlier and (2) to investigate if verbal fluency tasks can help to differentiate between patients with Mild Cognitive Impairment (MCI) who will progress to AD two years later (progress) and those who will not (non-progress). Method: A verbal fluency task was administered to 25 patients with MCI and their respective control subjects. All patients underwent a neuropsychological evaluation twice in order for us to follow up on their global cognitive status. The second time, eight of them converted to AD. Results: On the one hand, phonemic verbal fluency deteriorates earlier than semantic verbal fluency in MCI patients; on the other hand, although we found statistically significant differences between patients with MCI and AD in both types of fluency tasks, none were found when comparing the performance of progress and non-progress. Conclusions: These results point to a greater impairment in phonemic verbal fluency in MCI patients and its potential capacity to predict conversion to AD.

The cross-sectional and longitudinal associations between fruit intake and cognitive performance: the Chinese Healthy Dance Study

ObjectiveTo analyse the association between fruit consumption and cognitive performance in middle-aged and older adults in China. MethodsParticipants were drawn from the Chinese Square Dance Cohort. The cross-sectional dataset included 4316 individuals, with their first visit from August 2020 to August 2023. The longitudinal dataset included 1465 participants, with their first visit from August 2020 to December 2021 and follow-up visits from August 2022 to December 2023. Fruit consumption was assessed using a food frequency questionnaire. Standardised neuropsychological assessments were used to measure composite z-scores of cognitive performance, and prevalent and incident mild cognitive impairment. ResultsIn the cross-sectional analysis, higher quartiles of citrus fruit, drupe, berry, and tropical fruit consumption were associated with higher composite z-scores for cognitive performance and lower odds of prevalent mild cognitive impairment. In the longitudinal analysis, there was a positive association between higher quartiles of citrus fruit intake and the annual rate of change in the composite z-scores for cognitive performance; standardised regression coefficient (95 % confidence interval) for the highest compared with the lowest quartile was 0.05 (0.02–0.08). Moreover, an association between higher quartiles of citrus fruit intake and a lower risk of incident mild cognitive impairment was detected; in the comparison of the highest with the lowest quartile, the risk ratio (95 % confidence interval) was 0.56 (0.36–0.88). ConclusionsThe relationship between fruit consumption and cognition varies across the different categories of fruit. Cognitive benefits of citrus fruit consumption were found for middle-aged and older adults. Ascertaining this association might enhance comprehensive dietary recommendations for fruit consumption.

Deferiprone in Alzheimer Disease

Interventions that substantially slow neurodegeneration are needed to address the growing burden of Alzheimer disease (AD) to societies worldwide. Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target. To investigate whether the brain-permeable iron chelator deferiprone slows cognitive decline in people with AD. This phase 2, double-masked, placebo-controlled randomized clinical trial of 12-month duration was conducted at 9 sites in Australia between August 2, 2018, and April 1, 2023. Patients older than 54 years with amyloid-confirmed mild cognitive impairment or early AD (a Mini-Mental State Examination score of 20 or higher) were screened. Randomization was 2:1 and masked to participants and all study staff. Deferiprone 15 mg/kg twice a day or placebo administered orally for 12 months. The primary outcome was a composite cognitive measure assessed at baseline, 6 months, and 12 months using a neuropsychological test battery (NTB) of memory, executive function, and attention tasks. Secondary outcomes included change in brain iron burden measured by quantitative susceptibility mapping (QSM) magnetic resonance imaging (target engagement), brain volume changes (secondary efficacy measure), and adverse events (safety analysis). Of 167 patients screened for eligibility, 81 were included, with 53 randomly assigned to the deferiprone group (mean [SD] age, 73.0 [8.0] years; 29 male [54.7%]) and 28 to the placebo group (mean [SD] age, 71.6 [7.2] years; 17 male [60.7%]); 54 participants completed the study (7 [25.0%] withdrew from the placebo group and 20 [37.7%] from the deferiprone group). In an intention-to-treat analysis, participants in the deferiprone group showed accelerated cognitive decline on the NTB primary outcome (β for interaction = -0.50; 95% CI, -0.80 to -0.20) compared with placebo (change in NTB composite z score for deferiprone, -0.80 [95% CI, -0.98 to -0.62]; for placebo, -0.30 [95% CI, -0.54 to -0.06]). Secondary analysis revealed that this result was driven by worsening performance on executive function tests. The QSM confirmed that deferiprone decreased iron in the hippocampus compared with placebo (change in hippocampal QSM for deferiprone, -0.36 ppb [95% CI, -0.76 to 0.04 ppb]; for placebo, 0.32 ppb [95% CI, -0.12 to 0.75 ppb]; β for interaction = -0.68 [95% CI, -1.27 to -0.09]). Longitudinal hippocampal volume loss was not affected by deferiprone, but exploratory analysis of other brain regions revealed increased volume loss with deferiprone in frontal areas. The frequency of the adverse effect of neutropenia (4 participants [7.5%] in the deferiprone group) was higher than in similar studies (1.6%-4.4%). These trial findings show that deferiprone 15 mg/kg twice a day decreased hippocampal QSM and accelerated cognitive decline in patients with amyloid-confirmed early AD, suggesting that lowering iron with deferiprone is detrimental to patients with AD. ClinicalTrials.gov Identifier: NCT03234686.

Associations between sociodemographic and clinical characteristics and adherence to self-management behaviours among community-dwelling older adults with mild cognitive impairment.

Self-management is vital for individuals with mild cognitive impairment (MCI) to enhance cognitive health and mitigate the risk of dementia. However, maintaining consistent engagement in self-management strategies can be challenging for older adults with MCI. This study aimed to explore the associations between sociodemographic and clinical characteristics and adherence to self-management behaviours among community-dwelling older adults with MCI. A cross-sectional study involving 467 community-dwelling older adults with MCI was conducted from July to November 2022 across Nanjing, Xuzhou, and Lianyungang in Jiangsu Province, China. Data on sociodemographic and clinical characteristics, as well as self-management behaviours for MCI, were collected. Multiple linear and binary logistic regressions were employed to identify factors influencing self-management behaviours. Among the four recommended self-management behaviours for MCI, participants adopted an average of 1.37 ± 1.202 behaviours. Physical exercise (n = 239; 51.2%) was the most prevalent behaviour, followed by modifiable risk factors management (n = 156; 33.4%), cognitive training (n = 144; 30.8%), and cognitive function monitoring (n = 103; 22.1%). Higher education level (B = 0.286, P < 0.001), urban employee medical insurance (B = 0.621, P < 0.001), and non-smoking status (B = 0.389, P = 0.002) positively correlated with aggregate MCI self-management behaviours, while older age (B = -0.295, P < 0.001) had a negative association. Marital status, monthly income, employment status, gender, residence, and family history of cognitive disorders were also found to be associated with specific self-management behaviours for MCI. Enhancing adherence to self-management among community-dwelling older adults with MCI is critical. Sociodemographic and clinical factors should be considered to pinpoint at-risk populations and accordingly tailor support strategies.

Quality of Life in Mild Cognitive Impairment and Mild Dementia Associated with Alzheimer's Disease: A Systematic Review.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) have a profound impact on patients' quality of life (QoL), with progressive declines occurring as the disease advances. This systematic review aims to summarize the published evidence on patient-reported outcomes (PROs) in individuals with MCI due to AD and mild AD dementia. Comprehensive searches were conducted across five major databases to identify studies reporting on utility values, disutilities, and QoL measures in these patient populations. A total of 23 studies were included that utilized various QoL assessment tools, including EQ-5D (n = 14), SF-36/SF-12 (n = 4), and QOL-AD (n = 11). Reported EQ-5D scores ranged from 0.81 to 0.92 for patients with MCI and from 0.67 to 0.85 for those with mild AD, indicating a noticeable decline in QoL as the disease progresses. QOL-AD scores ranged from 33.8 to 42.5 for MCI and from 32.4 to 38.1 for mild AD, equally reflecting the greater impairment in QoL with disease advancement. Interventions were generally associated with smaller declines in PROs compared to placebo, suggesting a positive impact of treatment in mitigating QoL deterioration. The findings underscore the significant QoL differences between MCI and mild AD, emphasizing the potential benefit of early intervention to preserve QoL and delay disease progression. This review highlights the importance of continued research to better understand QoL in patients with MCI and mild AD dementia, particularly in terms of capturing comprehensive patient-reported outcomes and evaluating the effectiveness of interventions over time. These findings can contribute to a more informed approach in clinical practice and support decision-making in the management of early-stage AD.

Sensitive written hedgehog PICture Naming and Immediate Recall (PICNIR) as a valid and brief test of semantic and short-term episodic memory for very mild cognitive impairment.

Semantic and short-term episodic memory are impaired in some brain disorders including Alzheimer's disease. Development and validation of an almost self-administered, but cognitively demanding four-minute test identifying very mild cognitive impairment (vMCI). The innovative hedgehog PICture Naming and Immediate Recall (PICNIR) consisted of two parts. The first task was to write down the names of 20 black-and-white pictures to evaluate long-term semantic memory and language. The second task involves immediate recall and writing the names of as many previously named pictures as possible in one minute. The PICNIR is assessed using the number of naming errors (NE) and correctly recalled picture names (PICR). The PICNIR and a neuropsychological battery were administered to 190 elderly individuals living independently in the community. They were divided into those with vMCI (n = 43 with Montreal Cognitive Assessment (MoCA) 24 ± 3 points) and sociodemographically matched cognitively normal (CN) individuals (n = 147 with MoCA 26 ± 3). Both subgroups had predicted mean Mini-Mental State Examination scores of 28-29 points. Compared to CN, vMCI participants made more NE (0.3 ± 0.6 versus 0.6 ± 0.9; p = 0.02) and recalled fewer PICR (8.9 ± 2.2 versus 6.8 ± 2.2; p < 0.000001). Discriminative validity was satisfactory using the area under the ROC curve (AUC): 0.76 for PICR, 0.74 for MoCA, 0.67 for MoCA-five-word recall, and 0.59 for NE. The AUCs of PICR and MoCA were comparable and larger than those of MoCA five-point recall or NE. Logical Memory scores, RAVLT scores, Digit symbol, and animal fluency correlated with PICR. The picture-based PICNIR is an ultra-brief, sensitive cognitive test valid for assessing very mild cognitive impairment. Its effectiveness should be validated for other languages and cultures.

Identification of lncRNA in circulating exosomes as potential biomarkers for MCI among the elderly

BackgroundThe abnormal expression of lncRNA in elderly patients with mild cognitive impairment (MCI), and the ability of exosomes to stably carry non-coding RNAs provide a reliable physiological basis for exosomal lncRNA in plasma as a biomarker of MCI. MethodsThis case-control study enrolled 155 patients with MCI and 155 healthy controls from a community-based population aged≥60 years. The expression profiles of lncRNA and mRNA in plasma exosomes were analyzed and validated using high-throughput RNA sequencing and qRT-PCR. Pathway enrichment analysis were performed on differentially expressed transcripts to screen for target lncRNAs and genes. Multivariate logistic regression models were used to construct clinical predictive models. The receiver operating characteristic curve was used to analyze the predictive value, with an 184-sample external database validated. Results132 lncRNAs and 459 mRNAs were significantly changed in plasma exosomes of MCI patients compared to healthy controls. LINC001380, ENST00000484033, and ENST00000531087 were screened as candidate exo-lncRNAs for predicting MCI. In logistic regression models, odds ratios and 95%CI for target exo-IncRNAs in MCI patients compared to healthy controls were 1.15(1.03–1.28) for LINC001380, 1.21(1.10–1.34) for ENST00000484033, and 1.23(1.08–1.40) for ENST00000531087, respectively. ROC curve analysis showed that the AUC of the combined predicted probability of target lncRNAs was 70.0 %(64.1 %–76.0 %). In the external database, the AUC for the target genes ATP2A2 and PSEN1 was 69.5 %(61.8 %–77.15 %). ConclusionThis study provided evidence for the specific expression of plasma exosomal lncRNAs in MCI and its possible biological mechanism. The combined detection of the expression levels of lncRNA-LINC001380, lncRNA-ENST00000484033, and lncRNA-ENST00000531087 in plasma exosomes may provide early diagnosis and prevention of cognitive impairment.

Comparative study of insulin resistance surrogate indices to predict mild cognitive impairment among Chinese non-diabetic adults

ObjectiveThe study aims to investigate the associations of triglyceride glucose (TyG), TyG combined with body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and the risk of mild cognitive impairment (MCI) in individuals without diabetes aged 45 and above.MethodsThe most recent data in this study were from a cohort study, which sourced samples from the China Health and Retirement Longitudinal Study, spanning 2011 to 2018. The four indices’ associations with MCI risk were analyzed using logistic regression. The predictive capacity was measured using the receiver operating characteristic (ROC) curve.ResultsOver a 7-year follow-up, 1,261 individuals (31.34%) of the 4,027 participants developed MCI. Logistic regression analysis revealed significant associations between these surrogate indices and MCI. The findings for the highest quartile compared with the lowest quartile were as follows: TyG: 1.24 (95% CI: 1.02, 1.49); TyG-BMI: 1.38 (95% CI: 1.13, 1.68); METS-IR: 1.50 (95% CI: 1.09, 2.06); TG/HDL-C: 1.34 (95% CI: 1.10, 1.64). ROC analysis revealed that TyG, TyG-BMI, TG/HDL-C, and METS-IR demonstrated excellent discriminatory power for MCI, with area under the curve (AUC) values of 0.82 (95% CI: 0.80, 0.83), 0.82 (95% CI: 0.80, 0.83), 0.83 (95% CI: 0.80, 0.84), and 0.83 (95% CI: 0.80, 0.84), respectively. The four indices showed stronger ability to predict MCI risk in females compared to males.ConclusionElevated levels of four indices are positively correlated with MCI risk. TyG-BMI and METS-IR demonstrate stronger capabilities in identifying MCI across both male and female populations. This suggests that early intervention in patients with elevated IR surrogate indices may help reduce the MCI.

Diagnostic Accuracy of Combined Measurement of Serum Homocysteine, C-Reactive Protein, and Serum Ferritin in Mild Cognitive Impairments and Alzheimer's Disease.

Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023. Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared. The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01). The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI. Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.

Diagnostic Accuracy of Combined Measurement of Serum Homocysteine, C-Reactive Protein, and Serum Ferritin in Mild Cognitive Impairments and Alzheimer's Disease.

Evaluation of the diagnostic accuracy of combined detection of serum homocysteine (Hcy), C-reactive protein (CRP), and serum ferritin (SF) levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Descriptive study. Place and Duration of the Study: Clinical Laboratory Section, Affiliated Hospital of Hebei University, Baoding, Heibei, China, from May 2022 to June 2023. Data of 120 patients with memory decline were retrospectively collected. They were divided into an MCI group and an AD group. A further 50 healthy participants were used as a normal control (NC) group. Differences in the Hcy, CRP, and SF levels between the three groups were evaluated. The specificity, accuracy, and sensitivity of these three indices in the combined or single diagnosis of AD and MCI were compared. Their associations with the severity of AD and MCI were also compared. The AD group had the highest levels of Hcy, CRP, and SF (18.79 ± 4.50, 6.35 ± 2.04, and 355.69 ± 120.36), followed by MCI (16.75 ± 3.06, 4.58 ± 2.31, and 203.48 ± 12.76), and NC group (14.32 ± 2.06, 2.06 ± 0.76, and 98.46 ± 5.06), with statistically significant differences (all p <0.001). The diagnostic efficacy of AD for CRP was 98.50%, sensitivity was 96.00%, and specificity was 94.00%, which was higher than Hcy and SF. Tested together, the area under the ROC curve was 99.90%, specificity was 98.00%, and sensitivity was 98.00%. The diagnostic efficacy of SF for MCI had sensitivity of 100.00%, and specificity of 100.00%, which was higher than that of Hcy and CRP. When the three were combined for detection, the area under the curve of SF was 100.00%, sensitivity of 100.00%, and specificity of 100.00%. The levels of Hcy, CRP, and SF were positively correlated with the severity of AD (p <0.01), while negatively correlated with the mini-mental state examination (MMSE) score (p <0.01). The combined detection of Hcy, CRP, and SF improved the diagnostic accuracy of comorbid AD and MCI. Homocysteine, C-reactive protein, Cognitive impairment, Serum ferritin, Alzheimer's disease.

The Italian guideline on diagnosis and treatment of dementia and mild cognitive impairment.

Approximately 2 million people in Italy are currently living with dementia or mild cognitive impairment (MCI), and 4 million are involved as family members or caregivers. Considering the significant impact of dementia, the Italian Ministry of Health entrusted the Italian National Institute of Health (Istituto Superiore di Sanità) with the development of a guideline within the Italian National Guideline System (Sistema Nazionale Linee Guida, SNLG) on the diagnosis and treatment of dementia and MCI. The main objective was to provide evidence-based recommendations aimed at reducing the variability and ensuring the appropriateness of clinical practices throughout the whole care process from identification and diagnosis to the end of life for people with dementia (PwD) or MCI and their families/caregivers. The GRADE-ADOLOPMENT approach was used to adopt, adapt and update the guideline developed by the National Institute for Health and Care Excellence in 2018 (NG97). The methodology was based on the Methodological Handbook produced by the SNLG. A multidisciplinary panel of 29 experts and four representatives of family members/caregivers discussed and approved 47 review questions. Of these, 34 questions were adopted from the NG97, and 13 were new questions, including 10 questions referring to MCI. Systematic literature reviews were performed for each question, and a team of methodological and clinical experts qualitatively assessed and summarised results from included studies based on the GRADE approach. To facilitate the implementation and dissemination of the contents of this guideline, a care pathway and a leaflet dedicated to PwD or MCI and their families/caregivers were also developed. The literature review for this guideline included studies published up to November 2023. More than 1000 peer-reviewed publications were included, covering the following areas: (i) identification, diagnosis and post-diagnostic support; (ii) care models and care coordination; (iii) pharmacological interventions for cognitive symptoms; (iv) non-pharmacological interventions for cognitive symptoms; (v) non-cognitive symptoms, intercurrent illnesses and palliative care. The multidisciplinary panel discussed and approved 167 clinical practice recommendations and 39 research recommendations. Italy's first National Guideline on dementia and MCI addresses diagnosis, treatment and care within the National Healthcare System. It includes recommendations on pharmacological and non-pharmacological approaches, and emphasises tailored interventions, comprehensive cognitive assessment, staff training and palliative care. The guideline also underlines the need to involve PwD in decision-making and supporting caregivers throughout the entire course of the disease. Structured strategies for the dissemination and implementation of the guideline will be defined within the Italian Fund for Alzheimer and other Dementias 2024-2026. An interactive care pathway and a leaflet dedicated to PwD and their carers are already available. The guideline will be updated starting January 2027, but early updates may be planned in case of breakthrough advancements.

Development and Validation of Virtual Reality Cognitive Training for Older Adults with Mild Cognitive Impairment: Protocol for a Mixed-Methods Program Evaluation Study.

As research on cognitive training methods for older adults with mild cognitive impairment (MCI) progresses, fully immersive virtual reality cognitive training (fi-VRCT) has shown promise in enhancing cognitive function. However, its effectiveness in improving instrumental activities of daily living (IADL) and fostering independence is still unclear. This study aims to address these uncertainties by developing and validating a fi-VRCT program focused on IADL, with the goal of enhancing both cognitive function and IADL performance in older adults with MCI. This mixed methods program evaluation study consists of three phases: feasibility, intervention, and extension. In the feasibility phase, we will implement fi-VRCT in real-world community settings and invite 20 older adults with MCI to participate in a single training session. Participants will provide feedback through questionnaires and individual interviews. The intervention phase will involve a double-blind, cluster-randomized controlled trial with 52 older adults with MCI, who will be randomly assigned to either the fi-VRCT or control groups. Both groups will complete 16 sessions over eight weeks, with cognitive and functional performance assessed at various intervals. During the extension phase, feedback will be gathered from 26 participants who underwent fi-VRCT through focus group interviews and ongoing questionnaires. Quantitative and qualitative findings will be synthesized to refine the fi-VRCT program and elucidate training outcomes. Ultimately, fi-VRCT has the potential to enhance cognitive and functional abilities in older adults with MCI in community settings. Ethical approval has been obtained from the Research Ethics Committee at National Taiwan Normal University (202312EM009). The research findings will be disseminated through reputable, peer-reviewed journals and professional international conferences to engage and inform academic and clinical audiences. NCT06392412.

Comparing 30 Versus 60min Cognitively Loaded Physical Exercise on Cognitive Function and Physical Health in Community-Dwelling Older Adults With Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial.

Mild cognitive impairment (MCI) is characterized by a mild decline in cognitive function and represents a risk stage for dementia in community-dwelling older adults. Exercise and dual-task training have been used to improve physical health, psychosocial health, and cognitive and learning functions in various subjects. However, the optimal time for these interventions has yet to be clearly identified. This study investigated the effects of cognitively loaded physical exercise (CLPE) on cognitive function and physical health in community-dwelling older adults with mild cognitive impairment and compared the differences according to exercise time. Fifty-one community-dwelling aged 60years or older with MCI were randomly assigned to 30-min CLPE (30CLPE, n=17), 60-min CLPE (60CLPE, n=17), and control (n=17) groups. The CLPE program consisted of a twice-weekly exercise program for 8weeks. During the exercise, a dual task was performed to assess cognitive load. The control group performed a typical exercise program at a dementia center during the same period. The Korean version of the Montreal Cognitive Assessment was used to evaluate cognitive function, and various physical health factors were assessed using the handgrip dynamometer and pinch gauge, Senior Fitness Test, dynamic and static balance abilities, and gait variables. After the intervention, both the 30CLPE and 60CLPE groups showed significant improvements in cognitive function, upper limb strength, senior fitness, balance, and gait (p<0.05), while the control group showed no significant changes in any of the variables (p>0.05). In between-group comparisons, both CLPE groups showed significantly improved cognitive and physical functions compared to the control group (p<0.05). However, there was no significant difference between the 30 CLPE and 60 CLPE groups (p>0.05). The results of this study demonstrate that cognitively loaded physical exercise is effective in improving cognitive and physical function in individuals with MCI. Both the 30-min and 60-min sessions resulted in significant improvements, with no statistically significant differences observed between the two durations. This suggests that persistence and consistency of exercise may be more important than the duration of individual sessions. Clinical Trials.gov: KCT0009053.

Effectiveness of vestibular therapy as an adjunct to cognitive therapy to improve cognition in elderly with mild cognitive impairment (MCI)

The rapid global increase in aging populations is leading to a rise in age-related conditions like mild cognitive impairment (MCI), necessitating new treatment strategies. This study will conduct a double-blinded, three-arm, randomized controlled trial to evaluate the effectiveness of adding vestibular therapy to cognitive therapy (VT+CT) compared to cognitive therapy (CT) alone and a control group. Participants will be assigned to one of three groups: VT+CT, CT only, or a control group. The VT+CT group will receive vestibular rehabilitation exercises along with a computerized brain program, while the CT group will get only the computerized brain program. Primary outcomes will include electroencephalography (EEG), the Digit Symbol Substitution Test (DSST), and event-related potential (ERP-P300). Secondary outcomes will be the Stroop Color Word Test (SCWT), Trail-Making Test (TMT), and European Quality 5 Dimensions (EQ-5D-5L). This research aims to determine if VT+CT improves cognitive function in elderly individuals with MCI.

Association of lamina cribrosa thickness and hippocampal volume in Alzheimer's disease patients.

Alzheimer's disease (AD) is the most common cause of dementia and affects a large portion of the elderly population worldwide. To analyze the relationship between lamina cribrosa thickness (LCT) and hippocampal volume in patients with AD and mild cognitive impairment (MCI). The sample in the present study consisted of 20 recently diagnosed MCI patients, 20 recently diagnosed AD patients, and 20 matched healthy volunteers. Every patient underwent magnetic resonance imaging (MRI) scans. The VolBrain software (open-access platform for MRI brain analysis) was used to calculate the hippocampal volume. Optical coherence tomography was performed to measure the LCT. Analysis of variance and Pearson chi-squared tests were employed to assess the results. The lowest total hippocampal volume (p < 0.05) was in the AD group, which was 6.14 ± 0.66 mm3, while in the control group, it was 7.7 ± 9.65 mm3, and 6.69 ± 0.46 mm3 in the MCI group. In comparison to the rest of the groups, in the AD group, the LCT was the thinnest (202.17 ± 16.35 µm). As per the results of the study population as a whole, low hippocampal volume causes low LCT, which shows an important relationship (r: 0.41; p < 0.05). The current findings present evidence of the relationship between hippocampal volume and LCT in patients with AD and MCI.

Association of dietary choline intake with incidence of dementia, Alzheimer's disease and mild cognitive impairment: a large population-based prospective cohort study

ObjectiveExplore the associations between dietary choline intake and the incidence of dementia, Alzheimer's disease (AD), mild cognitive impairment (MCI), and current cognitive performance in the UK Biobank cohort. MethodsDietary choline intake was categorized into quartiles of consumption based on 24-hour dietary recalls, with units expressed as milligrams per day. Diagnoses of dementia, AD, and MCI were identified using ICD-9/10 codes. Current cognitive performance was assessed via the computerized touchscreen interface. After adjusting for sociodemographic factors, dietary and lifestyle behaviors, and comorbid conditions, Cox proportional hazards regression, logistic regression, and restricted cubic splines were used to analyze the association between choline intake and dementia or cognitive performance. ResultsAmong 125,594 participants (55.8% female), with a mean age of 56.1 years (range: 40 to 70 years) at baseline, and a median follow-up of 11.8 years, 1,103 cases of dementia (including 385 AD) and 87 cases of MCI were recorded. U-shaped associations were observed between choline intake and dementia and AD. Participants in the 2nd quartile of total choline intake had lower risks compared to those in the lowest quartile, with HR of 0.80 (95% CI: 0.67, 0.96) for dementia and 0.76 (0.58, 1.00) for AD. Moderate intake of choline derivative, including free choline (HR, 0.77; 95%CI, 0.65, 0.92), phosphatidylcholine (0.82; 0.68, 0.98), sphingomyelin (0.82; 0.69, 0.98) and glycerophosphocholine (0.83; 0.70, 1.00), were associated with a 17% to 23% lower odds of dementia. Additionally, moderate total choline intake was associated with an 8% to 13% lower odds of poor cognitive performance in visual attention (OR, 0.92; 95%CI, 0.86, 0.99), fluid intelligence (0.87; 0.82, 0.92), and complex processing speed (0.90; 0.84, 0.95). ConclusionsIn conclusion, our findings suggest that moderate dietary choline intake, ranging from 332.89 mg/d to 353.93 mg/d, is associated with lower odds of dementia and better cognitive performance.

Structural and functional alterations of the hippocampal subfields in T2DM with mild cognitive impairment and insulin resistance: A prospective study.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and is often accompanied by mild cognitive impairment (MCI). The detrimental effects of T2DM and IR on the hippocampus have been extensively demonstrated. Few studies have examined the effects of IR on structure and function of hippocampal subfields in T2DM-MCI patients. A total of 104 T2DM patients were recruited in this prospective study and divided into four groups (T2DM-MCI-higherIR, n = 17; T2DM-MCI-lowerIR, n = 32; T2DM-nonMCI-higherIR, n = 19; T2DM-nonMCI-lowerIR, n = 36). Structure and function MRI data were captured. Clinical variables and neuropsychological scores were determined for all participants. Hippocampal subfield volume and functional connectivity were compared among four groups. Partial correlation analysis was performed between imaging indicators, clinical variables, and neuropsychological scores in all patients. T2DM-MCI-higher IR group had the smallest volumes of bilateral hippocampal tail, right subiculum-body, right GC-ML-DG-body, and right CA4-body. IR in right hippocampal tail, right subiculum-body, and right GC-ML-DG-body exerted main effect. Furthermore, elevated functional connectivity was found between right subiculum-body and bilateral dorsolateral prefrontal cortex and right anterior cingulate-medial prefrontal cortex. Hippocampal subfield volume positively correlates with total cholesterol and triglycerides and negatively correlates with fasting insulin. The present study found that T2DM-MCI patients have structural and functional alterations in hippocampal subfields, and IR is a negative factor influencing the alteration of hippocampal subfields volume. These findings support the importance of IR in T2DM-MCI patients and might be potential neuroimaging biomarkers of cerebral impairment in T2DM-MCI patients.