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The Lancet. Public Health Jul 2024Some cohort studies have reported a decline in dementia prevalence and incidence over time, although these findings have not been consistent across studies. We reviewed... (Review)
Review
BACKGROUND
Some cohort studies have reported a decline in dementia prevalence and incidence over time, although these findings have not been consistent across studies. We reviewed evidence on changes in dementia prevalence and incidence over time using published population-based cohort studies that had used consistent methods with each wave and aimed to quantify associated changes in risk factors over time using population attributable fractions (PAFs).
METHODS
We searched for systematic reviews of cohort studies examining changes in dementia prevalence or incidence over time. We searched PubMed for publications from database inception up to Jan 12, 2023, using the search terms "systematic review" AND "dementia" AND ("prevalence" OR "incidence"), with no language restrictions. We repeated this search on March 28, 2024. From eligible systematic reviews, we searched the references and selected peer-reviewed publications about cohort studies where dementia prevalence or incidence was measured in the same geographical location, at a minimum of two timepoints, and that reported age-standardised prevalence or incidence of dementia. Additionally, data had to be from population-based samples, in which participants' cognitive status was assessed and where validated criteria were used to diagnose dementia. We extracted summary-level data from each paper about dementia risk factors, contacting authors when such data were not available in the published paper, and calculated PAFs for each risk factor at all available timepoints. Where possible, we linked changes in dementia prevalence or incidence with changes in the prevalence of risk factors.
FINDINGS
We identified 1925 records in our initial search, of which five eligible systematic reviews were identified. Within these systematic reviews, we identified 71 potentially eligible primary papers, of which 27 were included in our analysis. 13 (48%) of 27 primary papers reported change in prevalence of dementia, ten (37%) reported change in incidence of dementia, and four (15%) reported change in both incidence and prevalence of dementia. Studies reporting change in dementia incidence over time in Europe (n=5) and the USA (n=5) consistently reported a declining incidence in dementia. One study from Japan reported an increase in dementia prevalence and incidence and a stable incidence was reported in one study from Nigeria. Overall, across studies, the PAFs for less education or smoking, or both, generally declined over time, whereas PAFs for obesity, hypertension, and diabetes generally increased. The decrease in PAFs for less education and smoking was associated with a decline in the incidence of dementia in the Framingham study (Framingham, MA, USA, 1997-2013), the only study with sufficient data to allow analysis.
INTERPRETATION
Our findings suggest that lifestyle interventions such as compulsory education and reducing rates of smoking through country-level policy changes could be associated with an observed reduction, and therefore future reduction, in the incidence of dementia. More studies are needed in low-income and middle-income countries, where the burden of dementia is highest, and continues to increase.
FUNDING
National Institute for Health and Care Research Three Schools' Dementia Research Programme.
Topics: Humans; Cohort Studies; Dementia; Incidence; Prevalence; Risk Factors; Systematic Reviews as Topic
PubMed: 38942556
DOI: 10.1016/S2468-2667(24)00120-8 -
The Lancet. Public Health Jul 2024
Topics: Humans; Dementia; Risk Factors; Brain
PubMed: 38942548
DOI: 10.1016/S2468-2667(24)00123-3 -
NeuroImage Jun 2024The prediction of Alzheimer's disease (AD) progression from its early stages is a research priority. In this context, the use of Artificial Intelligence (AI) in AD has...
BACKGROUND
The prediction of Alzheimer's disease (AD) progression from its early stages is a research priority. In this context, the use of Artificial Intelligence (AI) in AD has experienced a notable surge in recent years. However, existing investigations predominantly concentrate on distinguishing clinical phenotypes through cross-sectional approaches. This study aims to investigate the potential of modeling additional dimensions of the disease, such as variations in brain metabolism assessed via [F]-fluorodeoxyglucose positron emission tomography (FDG-PET), and utilize this information to identify patients with mild cognitive impairment (MCI) who will progress to dementia (pMCI).
METHODS
We analyzed data from 1,617 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had undergone at least one FDG-PET scan. We identified the brain regions with the most significant hypometabolism in AD and used Deep Learning (DL) models to predict future changes in brain metabolism. The best-performing model was then adapted under a multi-task learning framework to identify pMCI individuals. Finally, this model underwent further analysis using eXplainable AI (XAI) techniques.
RESULTS
Our results confirm a strong association between hypometabolism, disease progression, and cognitive decline. Furthermore, we demonstrated that integrating data on changes in brain metabolism during training enhanced the models' ability to detect pMCI individuals (sensitivity=88.4%, specificity=86.9%). Lastly, the application of XAI techniques enabled us to delve into the brain regions with the most significant impact on model predictions, highlighting the importance of the hippocampus, cingulate cortex, and some subcortical structures.
CONCLUSION
This study introduces a novel dimension to predictive modeling in AD, emphasizing the importance of projecting variations in brain metabolism under a multi-task learning paradigm.
PubMed: 38942101
DOI: 10.1016/j.neuroimage.2024.120695 -
NeuroImage. Clinical Jun 2024Advanced age is the most important risk factor for Alzheimer's disease (AD), and carrier-status of the Apolipoprotein E4 (APOE4) allele is the strongest known genetic...
Advanced age is the most important risk factor for Alzheimer's disease (AD), and carrier-status of the Apolipoprotein E4 (APOE4) allele is the strongest known genetic risk factor. Many studies have consistently shown a link between APOE4 and synaptic dysfunction, possibly reflecting pathologically accelerated biological aging in persons at risk for AD. To test the hypothesis that distinct functional connectivity patterns characterize APOE4 carriers across the clinical spectrum of AD, we investigated 128 resting state functional Magnetic Resonance Imaging (fMRI) datasets from the Alzheimer's Disease Neuroimaging Initiative database (ADNI), representing all disease stages from cognitive normal to clinical dementia. Brain region centralities within functional networks, computed as eigenvector centrality, were tested for multivariate associations with chronological age, APOE4 carrier status and clinical stage (as well as their interactions) by partial least square analysis (PLSC). By PLSC analysis two distinct brain activity patterns could be identified, which reflected interactive effects of age, APOE4 and clinical disease stage. A first component including sensorimotor regions and parietal regions correlated with age and AD clinical stage (p < 0.001). A second component focused on medial-frontal regions and was specifically related to the interaction between age and APOE4 (p = 0.032). Our findings are consistent with earlier reports on altered network connectivity in APOE4 carriers. Results of our study highlight promise of graph-theory based network centrality to identify brain connectivity linked to genetic risk, clinical stage and age. Our data suggest the existence of brain network activity patterns that characterize APOE4 carriers across clinical stages of AD.
PubMed: 38941766
DOI: 10.1016/j.nicl.2024.103635 -
Science Advances Jun 2024Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a...
Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HTR) in regulating memory. Transgenic mice expressing a humanized mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HTRs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HTR agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HTR signaling regulates memory, which may inform the use of 5-HTR agonists in the treatment of dementia.
Topics: Animals; Humans; Receptor, Serotonin, 5-HT2C; Memory; Mice; Mice, Transgenic; Neuronal Plasticity; Alzheimer Disease; Hippocampus; Serotonin; Disease Models, Animal; CA1 Region, Hippocampal; Neurons; Serotonin 5-HT2 Receptor Agonists
PubMed: 38941473
DOI: 10.1126/sciadv.adl2675 -
Science Advances Jun 2024Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice...
Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice at an early stage. The enhanced production of DCA induces the up-regulation of the bile acid receptor Takeda G protein-coupled receptor (TGR5), which is also specifically increased in neurons of AD mouse brains at an early stage. The accumulation of exogenous DCA impairs cognitive function in wild-type mice, but not in TGR5 knockout mice. This suggests that TGR5 is the primary receptor mediating these effects of DCA. Furthermore, excitatory neuron-specific knockout of TGR5 ameliorates Aβ pathology and cognition impairments in AD mice. The underlying mechanism linking TGR5 and AD pathology relies on the downstream effectors of TGR5 and the APP production, which is succinctly concluded as a "p-STAT3-APH1-γ-secretase" signaling pathway. Our studies identified the critical role of TGR5 in the pathological development of AD.
Topics: Animals; Humans; Mice; Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Brain; Deoxycholic Acid; Disease Models, Animal; Mice, Knockout; Neurons; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 38941459
DOI: 10.1126/sciadv.ado1855 -
Medicine Jun 2024Taiwan is an aging society, and the number of people with dementia is rapidly increasing. Due to a decline in cognitive and physical function, older adults with dementia...
BACKGROUND
Taiwan is an aging society, and the number of people with dementia is rapidly increasing. Due to a decline in cognitive and physical function, older adults with dementia not only gradually lose the ability to complete daily living tasks on their own, but are also at a higher risk of falls and injurious falls. It is important to develop interventions that combine cognitive and exercise training for older adults with dementia to promote or maintain their cognitive and physical functions and reduce their risk of falls. This study aimed to investigate the feasibility and effect of cognitive-based board games and multi-component exercise interventions on cognitive function, physical fitness, and fall risk in older adults with dementia.
METHODS
This was a quasi-experimental study with a single-group pretest and post-test design. The study participants were 41 community-dwelling older adults with mild to moderate dementia. They received cognitive-based board games and multi-component exercise interventions once a week for 12 weeks. The interventions included 1 hour of exercise training and 1 hour of cognitive training. Scores for the Taiwan version of the Montreal Cognitive Assessment (MoCA-T), physical fitness, and the St. Thomas Risk Assessment Tool for Falling Elderly Inpatients (STRATIFY) were measured as outcome indicators at baseline and after the 12-week period.
RESULTS
The overall MoCA-T score increased significantly (effect size = 0.402), with participants with mild dementia showing a greater increase (effect size = 0.522) than those with moderate dementia (effect size = 0.310). Participants' physical fitness performance improved. Female participants exhibited significant improvements in the 30-second chair stand test (effect size = 0.483) and 8-foot up-and-go test (effect size = 0.437). The fall risk score decreased by 0.05 points, the change was not significant.
CONCLUSION
The cognitive-based board game and multi-component exercise interventions used in this study are beneficial for improving cognitive function and physical fitness in older adults with dementia. These interventions are feasible and suitable for promotion among community-dwelling and institution-dwelling older adults with mild cognitive impairment or dementia to delay the decline in cognitive and physical function.
Topics: Humans; Female; Male; Aged; Dementia; Feasibility Studies; Exercise Therapy; Accidental Falls; Aged, 80 and over; Taiwan; Cognition; Physical Fitness; Games, Recreational; Independent Living
PubMed: 38941425
DOI: 10.1097/MD.0000000000038640 -
Medicine Jun 2024Old age is associated with a higher risk of dementia. Psychosocial characteristics frequently affect cognitive function; however, the exact mechanism underlying the...
Effects of psychosocial characteristics on cognitive function in middle-aged and older adults: Focusing on change by year using the Korean Longitudinal Study of Aging panel data (2014-2018).
Old age is associated with a higher risk of dementia. Psychosocial characteristics frequently affect cognitive function; however, the exact mechanism underlying the effect of psychosocial factors on cognitive function is unclear. Therefore, this study aimed to investigate the effects of psychosocial characteristics on cognitive function. The participants comprised 4809 middle-aged and older (years 50+) adults. The analysis used data from the Korean Longitudinal Study of Aging from 2014 to 2018. The effects of neighborhood interaction, depression, life satisfaction, and economic activity on cognitive function were examined, and a linear mixed model analysis was performed to assess the change in cognitive function by year. A statistically significant association was found between neighborhood interaction and time. Additionally, cognitive function decreased in the presence of depression and with time. In men, significant interactions were found between depression and time and between economic activity and time. In women, significant interactions were found between life satisfaction and time. The findings indicate that since active neighborhood interaction positively affects cognitive function, it is necessary to develop various community-wide social activity programs for middle-aged and older adults. As depression is a risk factor for cognitive impairment, it is crucial to prevent cognitive decline through continuous management of depression. Given the positive effects of economic activity on cognitive function in men, it is essential to expand infrastructure to sustain economic activity by developing educational programs and creating job opportunities for middle-aged and older men.
Topics: Humans; Male; Female; Longitudinal Studies; Middle Aged; Republic of Korea; Aged; Cognition; Depression; Personal Satisfaction; Cognitive Dysfunction; Residence Characteristics; Aging; Risk Factors; Sex Factors; Aged, 80 and over
PubMed: 38941412
DOI: 10.1097/MD.0000000000038637 -
PloS One 2024This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented.
METHODS
Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants.
RESULTS
Study is ongoing and open to enrollment.
CONCLUSION
The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.
Topics: Humans; Electroconvulsive Therapy; Psychomotor Agitation; Dementia; Single-Blind Method; Female; Male; Treatment Outcome; Aged; Aberrant Motor Behavior in Dementia
PubMed: 38941338
DOI: 10.1371/journal.pone.0303894 -
Age and Ageing Jun 2024Dementia caregiving is a dynamic and multidimensional process. To gain a comprehensive understanding of informal caregiving for people living with dementia (PLWD), it is...
BACKGROUND
Dementia caregiving is a dynamic and multidimensional process. To gain a comprehensive understanding of informal caregiving for people living with dementia (PLWD), it is pivotal to assess the quality of life (QoL) of informal caregivers.
OBJECTIVE
To evaluate whether the care-recipient relationship type predicts changes in the QoL of informal caregivers of PLWD over a two-year period.
METHODS
This was a secondary analysis of longitudinal data. The data were drawn from two waves of linked data from the National Health and Aging Trends Study (NHATS) and the National Study of Caregiving (NSOC) (2015: NHATS R5 & NSOC II; 2017: NHATS R7 & NSOC III). Caregivers were categorized into spousal, adult-child, "other" caregiver and "multiple" caregivers. QoL was assessed through negative emotional burden (NEB), positive emotional benefits and social strain (SS). Generalized estimating equation modelling was used to examine changes in caregivers' QoL outcomes across types of relationship over time.
RESULTS
About, 882 caregivers were included who linked to 601 PLWD. After adjusting caregivers' socio-demographics, "other" caregivers had lower risk of NEB and SS than spousal caregivers (OR = 0.34, P = 0.003, 95%CI [0.17, 0.70]; OR = 0.37, P = 0.019, 95%CI 0.16, 0.85], respectively), and PLWD's dementia status would not change these significance (OR = 0.33, P = 0.003, 95%CI [0.16, 0.68]; OR = 0.31, P = 0.005, 95%CI [0.14, 0.71], respectively).
CONCLUSIONS
The study demonstrates that spousal caregivers face a higher risk of NEB and SS over time, underscoring the pressing need to offer accessible and effective support for informal caregivers of PLWD, especially those caring for their spouses.
Topics: Humans; Quality of Life; Dementia; Female; Male; Caregivers; Aged; Longitudinal Studies; Caregiver Burden; Middle Aged; Aged, 80 and over; Time Factors; Spouses
PubMed: 38941118
DOI: 10.1093/ageing/afae128