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1.
BMJ Open ; 14(7): e082404, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39002963

ABSTRACT

INTRODUCTION: The efficacy of multitarget neuroprotective drug DL-3-n-butylphthalide (NBP) in improving cognitive function has been confirmed in patients with vascular cognitive impairment without dementia. However, its efficacy in patients with symptomatic predementia phase of Alzheimer's disease remains uncertain. This study aims to evaluate the efficacy and safety of NBP in improving cognitive function in patients with mild cognitive impairment (MCI) through a clinical randomised controlled trail. METHODS AND ANALYSIS: This study is a 12-month, randomised, double-blind, placebo-controlled, multicentric trial, involving 270 patients with MCI. Subjects are randomly assigned to receive either NBP soft capsule (200 mg, three times per day) or placebo with an allocation ratio of 1:1. The efficacy and safety of NBP are assessed by comparing the results of neuropsychological, neuroimaging and laboratory tests between the two groups. The primary endpoint is the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale after 12 months. All patients will be monitored for adverse events. ETHICS AND DISSEMINATION: This study involving human participants has been reviewed and approved by Ethics Committee of Xuan Wu Hospital (No.2017058). The participants provide their written informed consent to participate in this study. Results will be published in peer-reviewed medical journals and disseminated to healthcare professionals at local and international conferences. PROTOCOL VERSION: V 3.0, 3 September 2022. TRIAL REGISTRATION NUMBER: ChiCTR1800018362.


Subject(s)
Benzofurans , Cognitive Dysfunction , Neuroprotective Agents , Humans , Benzofurans/therapeutic use , Benzofurans/adverse effects , Cognitive Dysfunction/drug therapy , Double-Blind Method , Male , Aged , Female , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/adverse effects , Middle Aged , Treatment Outcome , Randomized Controlled Trials as Topic , Neuropsychological Tests , Cognition/drug effects , Multicenter Studies as Topic
2.
J Am Geriatr Soc ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007450

ABSTRACT

BACKGROUND: With changing cognitive abilities, individuals with mild cognitive impairment (MCI) and dementia face challenges in successfully managing multidrug regimens. We sought to understand how individuals with MCI or dementia and their family caregivers manage multidrug regimens and better understand patient-to-caregiver transitions in medication management responsibilities. METHODS: We conducted qualitative interviews among patient-caregiver dyads. Eligibility included: patients with a diagnosis of MCI, mild or moderate dementia, managing ≥3 chronic conditions, ≥5 prescription medications, who also had a family caregiver ≥18 years old. Semi-structured interview guides, informed by the Medication Self-Management model, ascertained roles and responsibilities for medication management and patient-to-caregiver transitions in medication responsibilities. RESULTS: We interviewed 32 patient-caregiver dyads. Older adults and caregivers favored older adult autonomy in medication management, and individuals with MCI and mild dementia largely managed their medications independently using multiple strategies (e.g., establishing daily routines, using pillboxes). Among individuals with moderate dementia, caregivers assumed all medication-related responsibilities except when living separately. In those scenarios, caregivers set up organizers and made reminder calls, but did not observe family members taking medications. Patient-to-caregiver transitions in medication responsibilities frequently occurred after caregivers observed older adults making errors with medications. As caregivers sought to assume greater responsibilities with family members' medicines, they faced multiple barriers. Most barriers were dyadic; they affected both the older adult and the caregiver and/or the relationship. Some barriers were specific to caregivers; these included caregivers' competing responsibilities or inaccurate perceptions of dementia, while other barriers were related to the healthcare system. CONCLUSIONS: To ease medication management transitions, balance must be sought between preservation of older adult autonomy and early family caregiver involvement. Clinicians should work to initiate conversations with family caregivers and individuals living with MCI or dementia about transitioning medication responsibilities as memory loss progresses, simplify regimens, and deprescribe, as appropriate.

3.
Open Biol ; 14(7): 230419, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39013416

ABSTRACT

The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral Aß amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted cis-Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11, p = 1.8 × 10-3), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59, p = 1.5 × 10-5) and plasma tau concentration (0.06 log2(ng l-1) 95%CI 0.03; 0.08, p = 4.55 × 10-6). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.


Subject(s)
Genome-Wide Association Study , Neurodegenerative Diseases , Serum Amyloid P-Component , Humans , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/metabolism , Serum Amyloid P-Component/metabolism , Serum Amyloid P-Component/genetics , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/etiology , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease , Mendelian Randomization Analysis , Biomarkers , tau Proteins/metabolism , tau Proteins/genetics , Lewy Body Disease/genetics , Lewy Body Disease/metabolism , Male , Female
4.
BMJ Open ; 14(7): e082988, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013656

ABSTRACT

INTRODUCTION: COVID-19 vaccination is crucial for vulnerable people with underlying chronic conditions such as Alzheimer's disease and related dementias (ADRD) and mild cognitive impairment (MCI). These individuals face unique challenges, including higher risk of COVID-19, difficulties in adopting preventive behaviours and vaccine hesitancy due to concerns about adverse reactions. Therefore, efforts to promote vaccination, including boosters tailored to the currently circulating virus, are essential for people with ADRD/MCI. OBJECTIVE: The primary purpose of this study protocol is to conduct a comprehensive analysis of COVID-19 vaccination coverage and adverse reactions among individuals with ADRD/MCI in comparison to those without ADRD/MCI. Additionally, the proposed study aims to investigate the impact of social determinants of health on COVID-19 vaccination and vaccine hesitancy in individuals with ADRD/MCI. METHODS AND ANALYSIS: A retrospective cross-sectional study will be conducted utilising data from the All of Us (AoU) Researcher Workbench. Relevant data fields are extracted from sources including demographic information, COVID-19 Vaccine Survey, Basic Survey, Health Access & Utilization, Social Determinants of Health, and Electronic Health Record (EHR) data. Data on vaccination, adverse reactions and vaccine hesitancy will be collected through COVID-19 vaccine survey questionnaires. Propensity score matching and binary logistic regression will be applied to assess the vaccination rates and vaccine hesitancy, while controlling for demographic characteristics and social determinants of health factors. ETHICS AND DISSEMINATION: This study protocol received approval from the Institutional Review Board at Florida State University (STUDY00004571). Results will be disseminated through publication in peer-reviewed journals and presented at scientific conferences.


Subject(s)
COVID-19 Vaccines , COVID-19 , Social Determinants of Health , Vaccination Hesitancy , Humans , Cross-Sectional Studies , Retrospective Studies , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/psychology , Vaccination Hesitancy/psychology , Vaccination Hesitancy/statistics & numerical data , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , SARS-CoV-2 , Vaccination Coverage/statistics & numerical data , Cognitive Dysfunction/prevention & control , Alzheimer Disease/psychology , Dementia/psychology , Research Design , Male , Female
5.
Health Rep ; 35(7): 3-13, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018523

ABSTRACT

Background: Most individuals prefer to spend their final moments of life outside a hospital setting. This study compares the places of care and death of long-term care (LTC) home residents in Ontario in the last 90 days of life, according to LTC home rurality. Data and methods: This retrospective cohort study was conducted using health administrative data from ICES (formerly known as the Institute for Clinical Evaluative Sciences). The study population, which was identified through algorithms, included all Ontario LTC home residents with a dementia diagnosis who died between April 1, 2014, and March 31, 2019. The location of death was categorized as in an acute care hospital, an LTC home, a subacute care facility, or the community. Places of care included emergency department visits and hospitalizations in the last 90 days of life. Statistical tests were used to evaluate differences in location of death and places of care by rurality. Results: Of the 65,375 LTC home residents with dementia, 49,432 (75.6%) died in an LTC home. Residents of LTC homes in the most urban areas were less likely to die in an LTC home than those in more rural homes (adjusted relative risk: 0.84; 95% confidence interval: 0.83 to 0.85). A higher proportion of residents of the most urban LTC homes had at least one hospitalization in the last 90 days of life compared with rural residents (23.7% versus 9.9% palliative hospitalizations and 28.3% versus 15.9% non-palliative hospitalizations [p ⟨ 0.001]). Interpretation: Individuals with dementia residing in urban LTC homes are more likely to receive care in the hospital and to die outside a LTC home than their counterparts living in rural LTC homes. The findings of this work will inform efforts to improve end-of-life care for older adults with dementia living in LTC homes.


Subject(s)
Dementia , Long-Term Care , Nursing Homes , Rural Population , Humans , Dementia/mortality , Female , Male , Ontario/epidemiology , Retrospective Studies , Aged, 80 and over , Aged , Nursing Homes/statistics & numerical data , Terminal Care , Hospitalization/statistics & numerical data
6.
J Am Med Dir Assoc ; : 105129, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38977199

ABSTRACT

OBJECTIVES: There is currently no reliable tool for classifying dementia severity level based on administrative claims data. We aimed to develop a claims-based model to identify patients with severe dementia among a cohort of patients with dementia. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We identified people living with dementia (PLWD) in US Medicare claims data linked with the Minimum Data Set (MDS) and Outcome and Assessment Information Set (OASIS). METHODS: Severe dementia was defined based on cognitive and functional status data available in the MDS and OASIS. The dataset was randomly divided into training (70%) and validation (30%) sets, and a logistic regression model was developed to predict severe dementia using baseline (assessed in the prior year) features selected by generalized linear mixed models (GLMMs) with least absolute shrinkage and selection operator (LASSO) regression. We assessed model performance by area under the receiver operating characteristic curve (AUROC), area under precision-recall curve (AUPRC), and precision and recall at various cutoff points, including Youden Index. We compared the model performance with and without using Synthetic Minority Oversampling Technique (SMOTE) to reduce the imbalance of the dataset. RESULTS: Our study cohort included 254,410 PLWD with 17,907 (7.0%) classified as having severe dementia. The AUROC of our primary model, without SMOTE, was 0.81 in the training and 0.80 in the validation set. In the validation set at the optimized Youden Index, the model had a sensitivity of 0.77 and specificity of 0.70. Using a SMOTE-balanced validation set, the model had an AUROC of 0.83, AUPRC of 0.80, sensitivity of 0.79, specificity of 0.74, positive predictive value of 0.75, and negative predictive value of 0.78 when at the optimized Youden Index. CONCLUSIONS AND IMPLICATIONS: Our claims-based algorithm to identify patients living with severe dementia can be useful for claims-based pharmacoepidemiologic and health services research.

7.
Int J Geriatr Psychiatry ; 39(7): e6119, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39004777

ABSTRACT

OBJECTIVES: For many people with dementia and unpaid carers, using technology for care and support has become essential. Rapid proliferation of technology highlights the need to understand digital access to health and social care services for dementia. This mixed-methods systematic review aims to explore digital access to health and social care services for dementia, from the perspective of people with dementia and unpaid carers. METHODS: Nine electronic databases were searched in May 2023 for qualitative, quantitative, or mixed-method studies, published in English or German, focused on experiences of using technology-delivered health and social care services for people with dementia and unpaid carers. After removal of duplicates and screening, 44 empirical papers were included. RESULTS: From the 44 studies, findings were grouped into five categories, highlighting experiences for people with dementia and unpaid carers: (1) Adapting to technology, (2) Inequalities and variations in outcomes, (3) Impact on caring, (4) Impact on health, and (5) Impact on relationships. Proliferation of technology in care access emphasised the need for quick adaptation to technology and examination of its impact. The impact of such service delivery has evidenced mixed findings. There were improvements in the health and wellbeing of people with dementia and unpaid carers, and benefits for their dyadic relationship. However, using technology for health and social care access is not always possible and is often reliant on unpaid carers for support. Lower tech-literacy, lack of equipment or money to buy equipment and poor internet connection can impact the potential for positive outcomes. CONCLUSIONS: Technology can bring great benefits: social inclusion, improved service access and care. However, using technology in service delivery in dementia needs careful thought. Professionals and service providers need to be cognizant of the complex nature of dementia, and the benefits and challenges of hybrid service delivery.


Subject(s)
Caregivers , Dementia , Health Services Accessibility , Humans , Dementia/therapy , Dementia/diagnosis , Social Work , Telemedicine
8.
Article in English | MEDLINE | ID: mdl-39022830

ABSTRACT

BACKGROUND: High-dimensional propensity scoring (HDPS) is a method for empirically identifying potential confounders within large healthcare databases such as administrative claims data. However, this method has not yet been applied to large national health surveys such as the National Health and Aging Trends Study (NHATS), an ongoing nationally representative survey of older adults in the U.S and important resource in gerontology research. METHODS: In this Research Practice article, we present an overview of HDPS and describe the specific data transformation steps and analytic considerations needed to apply it to national health surveys. We applied HDPS within NHATS to investigate the association between self-reported visual difficulty and incident dementia, comparing HDPS to conventional confounder selection methods. RESULTS: Among 7,207 dementia-free NHATS wave 1 respondents, 528 (7.3%) had self-reported visual difficulty. In an unadjusted discrete time proportional hazards model accounting for the complex survey design of NHATS, self-reported visual difficulty was strongly associated with incident dementia (OR 2.34, 95% CI: 1.95-2.81). After adjustment for standard investigator-selected covariates via inverse probability weighting, the magnitude of this association decreased, but evidence of an association remained (OR 1.44, 95% CI: 1.11-1.85). Adding 75 HDPS-prioritized variables to the investigator-selected propensity score model resulted in further attenuation of the association between visual impairment and dementia (OR 0.94, 95% CI: 0.70-1.23). CONCLUSIONS: HDPS can be successfully applied to national health surveys such as NHATS and may improve confounder adjustment. We hope developing this framework will encourage future consideration of HDPS in this setting.

9.
Geriatr Psychol Neuropsychiatr Vieil ; 22(2): 241-253, 2024 Jun 01.
Article in French | MEDLINE | ID: mdl-39023159

ABSTRACT

Lewy body dementia (LBD) is the second most frequent neurodegenerative disorder after Alzheimer disease (AD). In this study, we compared functional decline between LBD and AD patients, considering motor dysfunction, over an 18-month follow-up period. We included all patients >70 years of age, with initial MMSE ≥ 20 and a diagnosis of possible or probable LBD or AD, who consulted at the memory centre of the Pitié-Salpêtrière hospital. Statistical analyses were performed using univariate tests and multivariate linear regression. Thirty-seven AD and 36 LBD patients were included, with a median age of 81 and a median MMSE score of 24/30. Global ADL Katz score decreased significantly for LBD people, compared to AD patients: -0.40 ± 0.75 versus 0 ± 0.24; p=0.003. Global IADL score decreased in the two populations but without a significant difference between the two groups: -1.71 ± 2.19 in LBD versus -1.32 (± 1.55); p=0.38. This study shows a significant decrease in autonomy in LBD patients over time that was faster than that in AD patients, related, in particular, to bathing, dressing and personal care.


Subject(s)
Activities of Daily Living , Alzheimer Disease , Lewy Body Disease , Humans , Lewy Body Disease/psychology , Lewy Body Disease/physiopathology , Alzheimer Disease/psychology , Male , Female , Aged , Aged, 80 and over , Disease Progression
10.
Alzheimers Dement ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023302

ABSTRACT

INTRODUCTION: Risk prediction models aim to identify those at high risk to receive targeted interventions. We aimed to identify the proportion of future dementia cases that would be missed by a high-risk screening program. METHODS: We identified validated dementia risk prediction models from systematic reviews. We applied these to European Prospective Investigation of Cancer Norfolk, a large population-based cohort of 30,387 individuals with 29 years of linked healthcare data. RESULTS: A maximum of 16.0% (14.7,17.2) and 31.9% (30.2,33.5) of cases arose from the highest risk decile and quintiles, respectively. For every 1000 people considered to be at high risk, a maximum of 235 (215, 255) developed dementia. DISCUSSION: Seven in every 10 cases of dementia arose from people at normal risk, and eight in every 10 people at high risk did not develop dementia. Individual-level prevention approaches targeted at high-risk groups are unlikely to produce large reductions in disease incidence at the population level. HIGHLIGHTS: Dementia, a significant public health challenge, is not an inevitability of aging; risk reduction is possible. Several dementia risk prediction models have been validated in the general population, and these aim to identify people at high risk of the disease who can then be targeted with primary prevention interventions. An alternative prevention approach is to focus on interventions that reduce risk across the population, irrespective of risk status. In our study, seven out of every ten people who developed dementia during 29 year follow-up were classed as 'normal-risk' (rather than 'high risk') at baseline. Eight out of every ten people who were at high risk at baseline did not go on to develop dementia. Even if effective, dementia risk reduction efforts based upon targeted high-risk approaches are unlikely to reduce incidence of disease at the population level.

11.
J Appl Gerontol ; : 7334648241261142, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023860

ABSTRACT

Caring for patients with dementia at risk of getting lost is challenging for community healthcare providers. Through semi-structured interviews with 25 participants, we examined the challenges faced by these providers and the strategies they employed. We identified the following themes of challenging parts: (a) the disturbance caused by behavioral and psychological symptoms in dementia; (b) difficulty in helping older family caregivers to keep the patient from going out; (c) difficulty in changing the attitudes of the family members; families' unawareness of the risk of getting lost. We also identified the following strategies to mitigate these themes: (a) detecting the risk of getting lost through early assessment; (b) encouraging the family to use resources or devices to prevent the patient from getting lost; (c) educating the family to manage behavior and psychological symptoms of dementia; (d) strengthening the patient's crisis awareness.

12.
J Appl Gerontol ; : 7334648241261454, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023911

ABSTRACT

In-depth understanding of dementia carer experience can assist clinicians by providing insight into dementia onset, symptoms and management, and help conceptualize and understand the pattern of dementia progress over time and what help is needed. We undertook a qualitative study to understand dementia carers experiences of providing care and reasons for admission to a residential aged care facility (RACF). Three themes were identified: (1) Challenges in the path to diagnosis and care, leading to delays accessing support; (2) Carer role impacted by living circumstances; and (3) Variation in decision support prior to admission to a RACF. Identifying dementia carer experiences, reinforces the need for more timely diagnosis, referral for support and interventions to promote better quality of life for a people living with dementia and their carer and to delay premature RACF placement.

13.
Clin Respir J ; 18(7): e13808, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39012086

ABSTRACT

BACKGROUND: Limited data is available regarding the weaning techniques employed for mechanical ventilation (MV) in elderly patients with dementia in China. OBJECTIVE: The primary objective of this study is to investigate diverse weaning methods in relation to the prognostic outcomes of elderly patients with dementia undergoing MV in the intensive care unit (ICU). Specifically, we seek to compare the prognosis, likelihood of successful withdrawal from MV, and the length of stay (LOS) in the ICU. METHODS: The study was conducted as a randomized controlled trial, encompassing a group of 169 elderly patients aged ≥ 65 years with dementia who underwent MV. Three distinct weaning methods were used for MV cessation, namely, the tapering parameter, spontaneous breathing trial (SBT), and SmartCare (Dräger, Germany). RESULTS: In the tapering parameter group, the LOS in the ICU was notably prolonged compared to both the SBT and SmartCare groups. However, no statistically significant differences were observed among the groups with respect to demographic characteristics, such as age and sex, as well as factors including the rationale for ICU admission, cause of MV, MV mode, oxygenation index, hemoglobin levels, albumin levels, ejection fraction, sedation and analgesia practices, tracheotomy, duration of MV, successful extubation, successful weaning, incidences of ventilator-associated pneumonia, and overall prognosis. CONCLUSIONS: Both the SBT and SmartCare withdrawal methods demonstrated a reduction in the duration of MV and LOS in the ICU when compared to the tapering parameter method. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900028449.


Subject(s)
Dementia , Intensive Care Units , Length of Stay , Respiration, Artificial , Ventilator Weaning , Humans , Ventilator Weaning/methods , Male , Female , Aged , Dementia/therapy , Respiration, Artificial/methods , Length of Stay/statistics & numerical data , China/epidemiology , Prognosis , Aged, 80 and over
14.
Biomed Hub ; 9(1): 83-88, 2024.
Article in English | MEDLINE | ID: mdl-39015200

ABSTRACT

Introduction: Older adults with dementia who are on multiple medications are more vulnerable to the use of potentially inappropriate medications (PIMs), which can significantly increase the risk of adverse events and drug-related problems. PIMs use is prevalent and varies among older adults with dementia or cognitive impairment (CI) attending memory clinics. However, the prevalence of PIMs, polypharmacy, and hyper-polypharmacy among older adults with dementia or CI who are attending memory clinics is not well understood. We will conduct a systematic review and meta-analyses to examine the overall estimate of the prevalence of the PIMs, polypharmacy, and hyper-polypharmacy use among older adults attending memory clinics, with dementia or CI. The secondary objective of this study will be to compile a list of commonly implicated PIMs and to investigate factors that may be associated with using PIMs in this population. Methods: Ovid MEDLINE, Ovid Embase, Scopus, Cochrane library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) will be systematically searched by a researcher (R.S.) with the help of a librarian (C.C.). All databases will be searched from inception to May 05, 2023. Cross-sectional, cohort, randomized clinical trials, quasi-experimental, and case-control studies will be included if they assess PIM's use among older adults with dementia and/or CI. A step-by-step guide by Pai et al. [Natl Med J India. 2004;17(2):86-95] will be followed when conducting this systematic review (S.R.). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist will be followed for reporting this SR. Conclusion: The findings from this SR/MA will identify the pooled prevalence of PIMs, providing a more precise estimate of the true prevalence of the PIMs, polypharmacy, hyper-polypharmacy in older adults with dementia or CI who are attending memory clinics at primary, secondary, or tertiary healthcare settings by considering the results of multiple studies.

15.
Dement Geriatr Cogn Dis Extra ; 14(1): 49-74, 2024.
Article in English | MEDLINE | ID: mdl-39015518

ABSTRACT

Introduction: Identifying individuals at high risk of dementia is critical to optimized clinical care, formulating effective preventative strategies, and determining eligibility for clinical trials. Since our previous systematic reviews in 2010 and 2015, there has been a surge in dementia risk prediction modelling. The aim of this study was to update our previous reviews to explore, and critically review, new developments in dementia risk modelling. Methods: MEDLINE, Embase, Scopus, and Web of Science were searched from March 2014 to June 2022. Studies were included if they were population- or community-based cohorts (including electronic health record data), had developed a model for predicting late-life incident dementia, and included model performance indices such as discrimination, calibration, or external validation. Results: In total, 9,209 articles were identified from the electronic search, of which 74 met the inclusion criteria. We found a substantial increase in the number of new models published from 2014 (>50 new models), including an increase in the number of models developed using machine learning. Over 450 unique predictor (component) variables have been tested. Nineteen studies (26%) undertook external validation of newly developed or existing models, with mixed results. For the first time, models have also been developed in low- and middle-income countries (LMICs) and others validated in racial and ethnic minority groups. Conclusion: The literature on dementia risk prediction modelling is rapidly evolving with new analytical developments and testing in LMICs. However, it is still challenging to make recommendations about which one model is the most suitable for routine use in a clinical setting. There is an urgent need to develop a suitable, robust, validated risk prediction model in the general population that can be widely implemented in clinical practice to improve dementia prevention.

16.
Brain Commun ; 6(4): fcae185, 2024.
Article in English | MEDLINE | ID: mdl-39015769

ABSTRACT

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with chromosome 9 open reading frame 72 [C9orf72] expansion, 119 with granulin [GRN] mutations and 60 with microtubule-associated protein tau [MAPT] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers). We computed the diffusion tensor image analysis along the perivascular space index by calculating diffusivities in the x-, y- and z-axes of the plane of the lateral ventricle body. Clinical stage and blood-based markers were considered. A subset of 180 participants underwent cognitive follow-ups for a total of 640 evaluations. The diffusion tensor image analysis along the perivascular space index was lower in symptomatic frontotemporal dementia (estimated marginal mean ± standard error, 1.21 ± 0.02) than in old non-carriers (1.29 ± 0.03, P = 0.009) and presymptomatic mutation carriers (1.30 ± 0.01, P < 0.001). In mutation carriers, lower diffusion tensor image analysis along the perivascular space was associated with worse disease severity (ß = -1.16, P < 0.001), and a trend towards a significant association between lower diffusion tensor image analysis along the perivascular space and higher plasma neurofilament light chain was reported (ß = -0.28, P = 0.063). Analysis of longitudinal data demonstrated that worsening of disease severity was faster in patients with low diffusion tensor image analysis along the perivascular space at baseline than in those with average (P = 0.009) or high (P = 0.006) diffusion tensor image analysis along the perivascular space index. Using a non-invasive imaging approach as a proxy for glymphatic system function, we demonstrated glymphatic system abnormalities in the symptomatic stages of genetic frontotemporal dementia. Such measures of the glymphatic system may elucidate pathophysiological processes in human frontotemporal dementia and facilitate early phase trials of genetic frontotemporal dementia.

17.
Front Psychiatry ; 15: 1437363, 2024.
Article in English | MEDLINE | ID: mdl-39015885

ABSTRACT

Frontotemporal dementia (FTD) affects the frontal and temporal lobes of the brain, leading to personality changes, language impairments, and behavioral disturbances, including impulsivity and disinhibition. Assessing responsibility and recidivism risk in forensic evaluations is challenging due to the evolving nature of FTD. Despite limited literature, we present a case of a 45-year-old man with no prior legal or medical history, who committed criminal acts due to behavioral changes linked to the behavioral variant of frontotemporal dementia (bvFTD). Initial assessment found him irresponsible, with a non-evaluable risk of recidivism. Subsequent evaluation showed a low recidivism risk based on clinical evolution. We discuss these findings considering existing literature and Swiss jurisprudence.

18.
J Am Med Dir Assoc ; 25(9): 105118, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950588

ABSTRACT

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

19.
Am J Epidemiol ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38949483

ABSTRACT

Dementia incidence is lower among Asian Americans than Whites, despite higher prevalence of type 2 diabetes, a well-known dementia risk factor. Determinants of dementia, including type 2 diabetes, have rarely been studied in Asian Americans. We followed 4,846 Chinese, 4,129 Filipino, 2,784 Japanese, 820 South Asian, and 123,360 non-Latino White members of a California-based integrated healthcare delivery system from 2002-2020. We estimated dementia incidence rates by race/ethnicity and type 2 diabetes status, and fit Cox proportional hazards and Aalen additive hazards models for the effect of type 2 diabetes (assessed 5 years before baseline) on age of dementia diagnosis controlling for sex/gender, educational attainment, nativity, height, race/ethnicity, and a race/ethnicity*diabetes interaction. Type 2 diabetes was associated with higher dementia incidence in Whites (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.40-1.52). Compared with Whites, the estimated effect of diabetes was larger in South Asians (2.26 [1.48-3.44]), slightly smaller in Chinese (1.32 [1.08-1.62]) and Filipino (1.31 [1.08-1.60]), and similar in Japanese (1.44 [1.15-1.81]) individuals. Heterogeneity in this association across Asian subgroups may be related to type 2 diabetes severity. Understanding this heterogeneity may inform prevention strategies to prevent dementia for all racial and ethnic groups.

20.
Prev Med Rep ; 43: 102772, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38952432

ABSTRACT

Objectives: This study aims to investigate the influence of socioeconomic status (SES) on variations in physical activity (PA) levels and diabetes-related cognitive dysfunction and impairment amidst disruptions caused by the COVID-19 pandemic. Methods: With the sample of old population, comprising about 20 thousand from the Fact-Finding Survey on the Status of Senior Citizens (FSSSC) released by Ministry of Health and Welfare of South Korea in 2017 and 2020, we empirically tested the direct and indirect effects of SES on cognitive dysfunction using structural equation modeling (SEM). Two SEMs provided the comparison on the effects of COVID-19. Results: Household income had a negative impact on the likelihood of dementia diagnosis via PA related diabetes during the pandemic (p < 0.001), whereas no effects of household income on dementia diagnosis were found in 2017, due to no direct effect of PA on diabetes confirmation in 2017. The disparity in PA based on SES becomes more prominent among the older individuals during the pandemic (z = 11.7) than 2017 (z = 6.0), emphasizing the significance of PA in mitigating diabetes-induced cognitive dysfunction during the pandemic. SES affects access to PA, contributing to diabetes-induced cognitive dysfunctions in the older population with lower SES during the pandemic. Conclusion: PA may serve as a preventive measure against diabetes-induced cognitive dysfunction and dementia in the older population. Thorough investigation of these mechanisms is imperative to establish the role of PA in preventing diabetes-induced cognitive impairment, particularly among the older population with lower SES.

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