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The Lancet. Public Health Apr 2024
Topics: Humans; Ill-Housed Persons; Dementia
PubMed: 38553138
DOI: 10.1016/S2468-2667(24)00044-6 -
JAMA Network Open Oct 2023Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of...
IMPORTANCE
Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.
OBJECTIVE
To examine the association between adult ADHD and the risk of dementia.
DESIGN, SETTING, AND PARTICIPANTS
This prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.
EXPOSURE
Adult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.
MAIN OUTCOME AND MEASURES
Cox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.
RESULTS
At the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P < .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P < .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P < .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.
CONCLUSIONS AND RELEVANCE
In this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.
Topics: Humans; Male; Adult; Female; Attention Deficit Disorder with Hyperactivity; Cohort Studies; Prospective Studies; Central Nervous System Stimulants; Dementia
PubMed: 37847497
DOI: 10.1001/jamanetworkopen.2023.38088 -
Alzheimer's Research & Therapy Jun 2024Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate...
BACKGROUND
Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia.
METHODS
We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia.
RESULTS
High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]).
CONCLUSIONS
Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.
Topics: Humans; Dementia; Mendelian Randomization Analysis; Male; Female; Video Games; Brain; Cognition; Aged; Prospective Studies; Middle Aged; Magnetic Resonance Imaging; United Kingdom; Incidence
PubMed: 38898507
DOI: 10.1186/s13195-024-01496-7 -
Scientific Reports Oct 2023Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this...
Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis.
Topics: Humans; Diagnosis, Differential; Magnetic Resonance Imaging; Alzheimer Disease; Biomarkers; Machine Learning; Algorithms
PubMed: 37833302
DOI: 10.1038/s41598-023-43706-6 -
The Journals of Gerontology. Series A,... Mar 2024Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD)...
BACKGROUND
Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown.
METHODS
This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers.
RESULTS
The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15-2.59) and 3.00 (95% CI: 2.61-3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64-0.74) for incident dementia, and 0.74 (95% CI: 0.66-0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314).
CONCLUSIONS
Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD.
Topics: Humans; Aged; Alzheimer Disease; Incidence; Aging; Risk Factors; Genetic Predisposition to Disease; Genetic Risk Score; Hand Strength
PubMed: 37804123
DOI: 10.1093/gerona/glad224 -
Alzheimer's & Dementia : the Journal of... Mar 2024A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle... (Review)
Review
A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.
Topics: Humans; Dementia; Cognitive Dysfunction; Delphi Technique; Systematic Reviews as Topic; Risk Factors; Risk Reduction Behavior; Hearing Loss
PubMed: 38159267
DOI: 10.1002/alz.13577 -
PLoS Genetics Sep 2023Brains are highly metabolically active organs, consuming 20% of a person's energy at resting state. A decline in glucose metabolism is a common feature across a number...
Brains are highly metabolically active organs, consuming 20% of a person's energy at resting state. A decline in glucose metabolism is a common feature across a number of neurodegenerative diseases. Another common feature is the progressive accumulation of insoluble protein deposits, it's unclear if the two are linked. Glucose metabolism in the brain is highly coupled between neurons and glia, with glucose taken up by glia and metabolised to lactate, which is then shuttled via transporters to neurons, where it is converted back to pyruvate and fed into the TCA cycle for ATP production. Monocarboxylates are also involved in signalling, and play broad ranging roles in brain homeostasis and metabolic reprogramming. However, the role of monocarboxylates in dementia has not been tested. Here, we find that increasing pyruvate import in Drosophila neurons by over-expression of the transporter bumpel, leads to a rescue of lifespan and behavioural phenotypes in fly models of both frontotemporal dementia and Alzheimer's disease. The rescue is linked to a clearance of late stage autolysosomes, leading to degradation of toxic peptides associated with disease. We propose upregulation of pyruvate import into neurons as potentially a broad-scope therapeutic approach to increase neuronal autophagy, which could be beneficial for multiple dementias.
Topics: Humans; Animals; Frontotemporal Dementia; Alzheimer Disease; Neuroglia; Pyruvic Acid; Drosophila; Glucose
PubMed: 37733679
DOI: 10.1371/journal.pgen.1010893 -
Journal of the American Heart... Nov 2023Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the... (Review)
Review
Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD-related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease-modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades-long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart-brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.
Topics: Humans; United States; Alzheimer Disease; Cardiovascular Diseases; Brain; Risk Factors; Inflammation
PubMed: 37929715
DOI: 10.1161/JAHA.123.030780 -
American Journal of Speech-language... Sep 2023The primary purpose of this study was to obtain preliminary evidence for a communication coaching intervention, Dementia Collaborative Coaching. The secondary aim of...
PURPOSE
The primary purpose of this study was to obtain preliminary evidence for a communication coaching intervention, Dementia Collaborative Coaching. The secondary aim of this study was to assess the acceptability, appropriateness, and feasibility of the intervention according to routine care providers.
METHOD
In a pre-/posttest design, speech-language pathologists (SLPs) delivered Dementia Collaborative Coaching to certified nursing assistants (CNAs) and people living with dementia (PLWD) in six different skilled nursing facilities over a period of 6 weeks. A self-perceived knowledge and efficacy measure regarding the use of external memory aids to support communication in PLWD was administered to CNA and SLP participants. The Cohen-Mansfield Agitation Inventory was administered to PLWD participants. The Acceptability of Intervention Measure, Intervention Appropriateness Measure, and Feasibility of Intervention Measure were administered post-intervention.
RESULTS
For CNAs, self-perceived knowledge and efficacy increased from pre-intervention ( = 3.73, = 0.69) to post-intervention ( = 4.07, = 0.44), (11) = -1.97, one-sided = .037. There was a significant improvement (e.g., reduction) in scores on the Cohen-Mansfield Agitation Inventory for PLWD ( = 10) from pre-intervention ( = 73.10, = 29.98) to post-intervention ( = 58.6, = 18.82), (9) = 2.83, = .01. CNA participants ( = 12) rated the intervention as acceptable ( = 4.48, = 0.48), appropriate ( = 4.33, = 0.61), and feasible ( = 4.19, = 0.48). SLPs rated the intervention as slightly more acceptable, appropriate, and feasible than CNAs with scores of = 4.54, = 0.51; = 4.54, = 0.51; and = 4.46, = 0.51, respectively.
CONCLUSIONS
Dementia Collaborative Coaching showed preliminary positive outcomes for CNAs and PLWD. The intervention was acceptable, appropriate, and feasible for routine providers and warrants further study.
Topics: Humans; Mentoring; Nursing Assistants; Certification; Communication; Dementia
PubMed: 37437528
DOI: 10.1044/2023_AJSLP-22-00367 -
Alzheimer's Research & Therapy Nov 2023Dementia is defined as a cognitive decline that affects functional status. Longitudinal ageing surveys often lack a clinical diagnosis of dementia though measure...
BACKGROUND
Dementia is defined as a cognitive decline that affects functional status. Longitudinal ageing surveys often lack a clinical diagnosis of dementia though measure cognition and daily function over time. We used unsupervised machine learning and longitudinal data to identify transition to probable dementia.
METHODS
Multiple Factor Analysis was applied to longitudinal function and cognitive data of 15,278 baseline participants (aged 50 years and more) from the Survey of Health, Ageing, and Retirement in Europe (SHARE) (waves 1, 2 and 4-7, between 2004 and 2017). Hierarchical Clustering on Principal Components discriminated three clusters at each wave. We estimated probable or "Likely Dementia" prevalence by sex and age, and assessed whether dementia risk factors increased the risk of being assigned probable dementia status using multistate models. Next, we compared the "Likely Dementia" cluster with self-reported dementia status and replicated our findings in the English Longitudinal Study of Ageing (ELSA) cohort (waves 1-9, between 2002 and 2019, 7840 participants at baseline).
RESULTS
Our algorithm identified a higher number of probable dementia cases compared with self-reported cases and showed good discriminative power across all waves (AUC ranged from 0.754 [0.722-0.787] to 0.830 [0.800-0.861]). "Likely Dementia" status was more prevalent in older people, displayed a 2:1 female/male ratio, and was associated with nine factors that increased risk of transition to dementia: low education, hearing loss, hypertension, drinking, smoking, depression, social isolation, physical inactivity, diabetes, and obesity. Results were replicated in ELSA cohort with good accuracy.
CONCLUSIONS
Machine learning clustering can be used to study dementia determinants and outcomes in longitudinal population ageing surveys in which dementia clinical diagnosis is lacking.
Topics: Humans; Male; Female; Middle Aged; Aged; Longitudinal Studies; Aging; Cognitive Dysfunction; Cognition; Dementia
PubMed: 38031083
DOI: 10.1186/s13195-023-01357-9