Henry Brodaty’s research while affiliated with University of South Wales and other places


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Publications (973)


AUC of the DemNCD-LR tool following logistic regression associated with the diagnosis of dementia, MI, stroke, and diabetes
A single risk assessment for the most common diseases of ageing, developed and validated on 10 cohort studies
  • Article
  • Full-text available

October 2024

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29 Reads

BMC Medicine

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Background We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors. Methods Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. Disease-free participants at baseline were included, and 22 risk factors (sociodemographic, medical, lifestyle, laboratory biomarkers) were evaluated. Two risk tools (DemNCD and DemNCD-LR based on Fine and Gray sub-distribution and logistic regression [LR], respectively) were developed and validated. Predictive accuracies of these risk tools were assessed using Harrel’s C-statistics and area under the curve (AUC) and 95% confidence interval (CI). Model calibration was conducted using Hosmer–Lemeshow goodness of fit test along calibration plots. Results Both the DemNCD and DemNCD-LR resulted in similar predictive accuracy for each outcome. The overall AUC (95% CI) for dementia, stroke, MI, and diabetes risk tool were 0·68 (0·65, 0·70), 0·58 (0·54, 0·61), 0·65 (0·61, 0·68), and 0·68 (0·64, 0·72), respectively, for males. For females, these figures were 0·65 (0·63, 0·67), 0·55 (0·52, 0·57), 0·65 (0·62, 0·68), and 0·61 (0·57, 0·65). Conclusions The DemNCD is the first tool to predict both dementia and multiple cardio-metabolic diseases using comprehensive risk factors and provided similar predictive accuracy to existing risk tools. It has similar predictive accuracy as tools designed for single outcomes in this age-group. DemNCD has the potential to be used in community and clinical settings as it includes self-reported and routinely available clinical measures.

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Meta-analyses results overview
Phenogram illustrating loci associated with each of the brain volumes under study at the common genome-wide significance threshold (P < 5 × 10⁻⁸). a, Left hemisphere interior. b, Left hemisphere exterior. c, Right hemisphere interior. d, Right hemisphere exterior. e, Both hemispheres upper. The P values referenced here correspond to a two-tailed z test as implemented in the Multi-Trait Analysis of GWAS method.
Polygenic prediction in the ABCD cohort
Barplots show the variance explained by intracranial and subcortical brain volume polygenic scores using the SBayesR approach with a linear mixed-effects model implemented in GCTA for the whole sample (n = 10,440) and individuals of European (n = 5,267), non-European (n = 5,173), African-only (n = 1,833) and Asian-only (n = 152) ancestries. The P value of the association is shown at the top of each bar; those with an asterisk (*) were significant after Bonferroni multiple-testing correction (0.05/50 (total number of tests) = 1 × 10⁻³). Non-European ancestry individuals include, but are not limited to, African-only and Asian-only ancestries as individuals with admixed ancestry were also included. P values in this figure correspond to Wald tests (two-sided) derived from the linear mixed model results.
Genetic overlap with neuropsychiatric traits and disorders
Heatmap depicting genetic correlations (rG) of intracranial and subcortical brain volumes with complex human phenotypes. *P < 0.05 and **P value significant after Bonferroni multiple-testing correction (0.05/320 (total number of genetic correlation tests) = 1.56 × 10⁻⁴). Genetic correlations were estimated using LDSC. P values correspond to chi-squared tests with one degree of freedom as implemented in LDSC.
Genetic structure of subcortical brain volumes
Path diagram of a three-factor model estimated with genomic SEM. Blue rectangles represent the genetic component of each subcortical brain volume. Green circles represent latent factors. Standardized path coefficients are presented.
Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

October 2024

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156 Reads

Nature Genetics

Luis M. García-Marín

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Miguel E. Rentería

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.


The Usefulness of the Regression-Based Normed SKT Short Cognitive Performance Test in Detecting Cognitive Impairment in a Community Sample

October 2024

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16 Reads

Diagnostics

Background: The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated. This study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI), and dementia (1) and to cross-validate the new norms for detecting MCI and dementia in a community sample of older adults with clinical diagnoses (2). Methods: The validation sample included 143 older adults (mean age = 87.7, SD = 3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia solely based on a consensus diagnosis; in addition, three tests (SKT, Mini-Mental State Examination (MMSE), and Addenbrooke’s Cognitive Examination III (ACE-III)) to measure cognitive impairment were applied. Sensitivity and specificity for all three tests, as well as bivariate correlations, were calculated. Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 70.3% for all three diagnostic groups. All correlations between the three tests and the consensus diagnosis were significant (p < 0.01). Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).


Two simple modifications to the World Falls Guidelines algorithm improves its ability to stratify older people into low, intermediate and high fall risk groups

October 2024

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53 Reads

Age and Ageing

Background We conducted a secondary analysis of a cohort study to examine the World Falls Guidelines algorithm’s ability to stratify older people into sizable fall risk groups or whether minor modifications were necessary to achieve this. Methods Six hundred and ninety-three community-living people aged 70–90 years (52.4% women) were stratified into low, intermediate and high fall risk groups using the original algorithm and a modified algorithm applying broader Timed Up and Go test screening with a >10-s cut point (originally >15 s). Prospective fall rates and physical and neuropsychological performance among the three groups were compared. Results The original algorithm was not able to identify three sizable groups, i.e. only five participants (0.7%) were classified as intermediate risk. The modified algorithm classified 349 participants (50.3%) as low risk, 127 participants (18.3%) as intermediate risk and 217 participants (31.3%) as high risk. The sizable intermediate-risk group had physical and neuropsychological characteristics similar to the high-risk group, but a fall rate similar to the low-risk group. The high-risk group had a significantly higher rate of falls than both the low- [incidence rate ratio (IRR) = 2.52, 95% confidence interval (CI) = 1.99–3.20] and intermediate-risk groups (IRR = 2.19, 95% CI = 1.58–3.03). Conclusion A modified algorithm stratified older people into three sizable fall risk groups including an intermediate group who may be at risk of transitioning to high fall rates in the medium to long term. These simple modifications may assist in better triaging older people to appropriate and tailored fall prevention interventions.


Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts

October 2024

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52 Reads

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1 Citation

JAMA Network Open

Importance Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. Objective To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up. Design, Setting, and Participants The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024. Exposure Incident stroke. Main outcomes and measures The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores. Results The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (−0.25 SD; 95% CI, −0.33 to −0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from −0.17 SD to −0.22 SD), as well as accelerated decline in global cognition (−0.038 SD per year; 95% CI, −0.057 to −0.019 SD per year) and all domains except memory (ranging from −0.020 to −0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was −0.049 SD per year (95% CI, −0.051 to −0.047 SD) in global cognition. Conclusions and relevance In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.


Social health markers in the context of cognitive decline and dementia: an international qualitative study

September 2024

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42 Reads

Frontiers in Psychiatry

Background Social health in the context of dementia has recently gained interest. The development of a social health conceptual framework at the individual and social environmental levels, has revealed a critical need for a further exploration of social health markers that can be used in the development of dementia intervention and to construct social health measures. Objective To identify social health markers in the context of dementia. Method This international qualitative study included six countries: Australia, Germany, Indonesia, Italy, Poland, and the Netherlands. Using purposive sampling, three to five cases per country were recruited to the study, with each case consisting of a person living with dementia, a primary informal caregiver, an active network member, and a health care professional involved in the care of the person with dementia. In-depth interviews, using an agreed topic guide, and content analysis were conducted to identify known and new social health markers. The codes were then categorized against our conceptual framework of social health. Results Sixty-seven participants were interviewed. We identified various social health markers, ranging from those that are commonly used in epidemiological studies such as loneliness to novel markers of social health at the individual and the social environmental level. Examples of novel individual-level markers were efforts to comply with social norms and making own choices in, for example, keeping contact or refusing support. At a social environmental level, examples of novel markers were proximity (physical distance) and the function of the social network of helping the person maintaining dignity. Conclusions The current study identified both well-known and novel social health markers in the context of dementia, mapped to the social health framework we developed. Future research should focus on translating these markers into validated measures and on developing social health focused interventions for persons with dementia.



O01 LISTEN TO YOUR HEART AND MIND: A FEASIBILITY STUDY ON COMBINED SCREENING OF RAISED BLOOD PRESSURE, ATRIAL FIBRILLATION, COGNITIVE IMPAIRMENT AND HEARING LOSS

September 2024

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11 Reads

Journal of Hypertension

Background and Objective Detection rates of hypertension continues to be suboptimal worldwide. The risk of hypertension increases substantially in older adults aged ≥65 years, a group also at increased risk of atrial fibrillation (AF), cognitive decline and hearing loss—all factors associated with hypertension. This pilot study aimed to 1) implement a combined screening strategy for these health conditions, and 2) assess feasibility and acceptability of the combined screening. Methods Adults aged ≥65 years without a prior diagnosis of cognitive impairment and dementia were invited to attend a combined screening appointment through advertisements posted in university and community group newsletters and noticeboards. Participants underwent blood pressure (BP) and AF screening using an oscillometric BP monitor with AF detection (Microlife WatchBP Office 2G), cognitive assessment (General Practitioner Assessment of Cognition, GPCOG), and audiometric testing. A subset of participants was invited to participate in a post-study process evaluation interview. Results Of the 35 participants (age 73±6 years, 51% females), 26 (74%) had hypertension (on antihypertensive medication: n=20; measured: n=6; unaware: n=2; uncontrolled: n=4). Possible AF was detected in two participants and seven had possible cognitive decline (GPCOG score <9). Hearing loss was detected in 13 participants. Interviews (n=16, 50% females) revealed that combined screening was acceptable and feasible as participants felt it was “convenient”, “saves time”, “a brilliant idea”, and that “… conditions are related and therefore appropriate to be together”. Most participants were already aware of their hypertension status, thus screening did not result in increased hypertension awareness except for one with uncontrolled hypertension who proceeded to purchase a home BP monitor. One participant with detected AF visited a cardiologist and confirmed non-AF arrhythmia. All interviewees found the appointment duration (approximately 60-75 minutes) was not too long nor too taxing. Conclusions Combined screening in older adults with increased cardiovascular risk is feasible and acceptable and should be considered for future screening programs in older adults.


Does Mild Functional Impairment Predict Dementia in Older Adults With Normal Cognition?

August 2024

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10 Reads

Alzheimer Disease & Associated Disorders

Objectives Functional impairment can be an early indicator of cognitive decline. However, its predictive utility in cognitively normal (CN) older adults remains unclear. This study aimed to determine whether mild functional impairment (MFI) in CN older adults could predict incident dementia over 6 years, in addition to assessing its association with cognitive performance. Design A longitudinal study with a 6-year follow-up. Participants A cohort of 296 community-dwelling CN older adults. Measurements MFI was defined by cutoffs for impairment on an objective performance-based and/or subjective questionnaire-based functional assessment. Cox regression analysis was conducted to assess the relationship between MFI and risk of incident dementia and cognitive performances over 6 years. Linear regression analysis examined the association between MFI and baseline cognitive performance. Results There were no significant longitudinal associations between MFI and incident dementia or changes in cognitive performance over 6 years. Defining MFI using both performance-based and informant-reported assessments was predictive of dementia. Cross-sectional analyses demonstrated significant associations between MFI and poorer baseline global cognition and performance in attention, visuospatial ability, and executive functioning. Conclusions CN older adults with MFI were not at an increased risk of developing dementia over 6 years. A definition of functional impairment requiring both performance-based and informant-based assessments may be useful in predicting dementia.


Highlights from the Razem przed siebie campaign and the Polish logo.
Survey data. (A) Time spent on the website; (B) Information read; (C) Website helpfulness; (D) Website information source; (E) Ease of use; (F) Plan to visit the website again.
Qualitative themes arrangement.
Fostering social health of people with dementia: evaluation of the Razem przed siebie dementia awareness campaign in Poland

August 2024

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37 Reads

Background Due to the need to increase social awareness about dementia and the needs of patients living with dementia in Poland, the Razem przed siebie (eng. Forward with Dementia) campaign was created. The aim of the study was to evaluate its effectiveness. Methods To disseminate key campaign messages to the target audiences (people with dementia, carers, health and social care professionals [HSCP] and general public) a website, social and traditional media promotions, webinars and social activities were created. The campaign ran between September 2021 and April 2022. Mixed methods (online survey, reach estimates and interviews) were used to evaluate the campaign. Results Almost 1,300 people visited the website during the campaign period. Of these, 55 carers and HSCP responded to the online survey. The most read section of the website was Understanding the diagnosis (carers [56% of 25] and HSCP [80% out of 30]). The website was mostly accessed by carers (68%) and HSCP (66.7%) through word-of-mouth recommendations. 80% carers and 90% HSCP found the website very or extremely helpful. Over 90% of carers and HSCP expressed an intention to revisit the website. Based on 31 interviews, campaign effects, change mechanisms and limitations were identified. Campaign events elicited positive emotions among people with dementia, providing them with a feeling of belonging and engagement. Esteeming personal interactions over informational campaign materials, those with dementia felt acknowledged and empowered by the events. Carers also reported positive experiences and increased interest and knowledge, though they expressed disappointment with the lack of respite care, an issue beyond the campaign’s scope. HSCP perceived the campaign events positively and identified significant gaps in the dementia care system. Conclusion Evaluation of the Razem przed siebie campaign revealed successes and limitations. While effectively incorporating anti-stigma campaign recommendations and enhancing social health for individuals with dementia, the campaign clearly showed the pressing need for systemic solutions. Despite positive perception of the campaign, there is a need for a better diagnostic and post-diagnostic support for people with dementia and their carers.


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Citations (33)


... In a recent multicentre randomised controlled trial, Xiao et al. (2024) demonstrated the effectiveness of the Chinese version of iSupport for dementia family caregivers. The researchers found that the intervention based on iSupport significantly improved the family caregivers' mental-health-related quality of life and self-efficacy, indicating a strong necessity to promote it among Chinese family caregivers. ...

Reference:

Exploring Stakeholder Perspectives on the Implementation of WHO iSupport for Dementia Program: A Qualitative Study
The effects of a facilitator-enabled online multicomponent iSupport for dementia program: A multicentre randomised controlled trial

International Journal of Nursing Studies

... 31,32 Therefore, we also applied a second, more recent brain age model developed by the CentileBrain team with a training set that more closely matches the mean age of the current sample (https://centilebrain.org/#/brainAge2). 33 Briefly, the CentileBrain model was trained separately in healthy females (N=9,185) and males (N=8,328) aged 5-40 years from multiple cohorts from the ENIGMA-Lifespan consortium. ...

Brain‐age prediction: Systematic evaluation of site effects, and sample age range and size

... Previous long-term follow-up studies have found that obesity would increase the risk of dementia onset, 2 and cognitive decline was associated with the deterioration of brain elasticity and accelerated ageing which may be related to changes in brain volume. [3][4][5] However, few studies have shown the associations between different obesity types and brain volumes in Asians. ...

Exploring the Link between Brain Topological Resilience and Cognitive Performance in the Context of Aging and Vascular Risk Factors: A Cross-Ethnicity Population-Based Study
  • Citing Article
  • April 2024

Science Bulletin

... As a result, several studies have recently emerged presenting different normative models for brain morphometry [12][13][14][15][16][17][18] . ...

Normative modelling of brain morphometry across the lifespan with CentileBrain: algorithm benchmarking and model optimisation

The Lancet Digital Health

... Informal carers, who often handle the coordination of treatment and care, have limited respite options (11). The few scientific studies on the social situation of people with dementia in Poland reveal that awareness of dementia is generally low among the general population as well as HSCP (12)(13)(14). Given the rising number of dementia cases, this lack of awareness constitutes a serious barrier to improving the situation for people with dementia in Poland (12). ...

Biomedical knowledge of dementia is not enough to counteract its stigma - quantitative research among future medical and social care staff in Poland
  • Citing Article
  • February 2024

Aging and Mental Health

... These findings suggest that our program's emphasis on providing individualized feedback based on participants' dementia risk profiles can contribute to a more positive outlook regarding their risk of developing dementia. Previous research has shown that personalized feedback leads to greater understanding and acceptance of risk factors (49), empowers individuals to take control of their health (31,52), increases awareness of potential consequences (53), and builds positive health behaviors (54). Future research should further examine the relative advantages of interventions incorporating personalized feedback compared to those lacking such feedback, aiming to identify the optimal approach. ...

FC5: The Maintain Your Brain online multidomain intervention for dementia risk reduction: qualitative exploration of lifestyle changes made, continued, or declined, and why
  • Citing Conference Paper
  • February 2024

International Psychogeriatrics

... Individuals with the Met allele of the BDNF Val66Met polymorphism tend to have reduced activity-dependent secretion of BDNF, which correlates with poorer episodic memory performance and hippocampal function. This effect is particularly pronounced in elderly populations and is modulated by factors such as physical activity (Canivet et al. 2015;Mei et al. 2024). ...

Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance

Alzheimer's Research & Therapy

... Beyond Saudi Arabia, Paul et al. revealed moderate dementia knowledge (mean 5.3 out of 7) among healthcare professionals in Qatar, with a lack of awareness about recent pathophysiological advances [18]. Pham et al. also noted poor dementia knowledge and low confidence levels among primary care providers in Vietnam [19]. ...

Knowledge, attitudes and self-confidence with skills required for providing dementia care in physicians at primary healthcare settings in Vietnam

BMC Health Services Research

... Based on an umbrella review and Delphi expert study, three additional factors were recently identified and included in an updated LIBRA score (LIBRA2), now also including hearing impairment, social contact, and sleep. 15 The objective of the present study is to compare the performance of the original and updated LIBRA score for predicting the risk of incident dementia in two large, longitudinal population-based aging studies. ...

Umbrella review and Delphi study on modifiable factors for dementia risk reduction

... Our pilot and main RCTs of I-HARP with community dwelling people with dementia and their informal carers, demonstrated strong, consistent results in terms of feasibility, appropriateness and adequacy of the study design, procedures, screening, recruitment, consent (~75% eligible dyads consented) and program adherence (~90% completed and complied) (Jeon, Krein, et al. 2020, Jeon, Simpson, et al. 2019. The post hoc sub-group analysis of 66 participants with mild dementia from the main I-HARP trial found significantly better functional independence in the intervention group both at 4 months and 12 months compared to the control group (Jeon, Simpson, et al. 2023). These results highlight the potential benefit of an interdisciplinary team administering evidence-based, tailored interventions as part of effective case management to have maximum impact on improving individuals' functional independence and wellbeing in early/mild stages of dementia and reducing falls, hospital transfers and institutionalisation (Jeon, Krein, et al. 2020, Jeon, Simpson, et al. 2023. ...

Effectiveness of the Interdisciplinary Home‐bAsed Reablement Program (I‐HARP) on improving functional independence of people living with dementia and process outcomes
  • Citing Article
  • December 2023