@article {10050, title = {Associations between self-reported sensory impairment and risk of cognitive decline and impairment in the Health and Retirement Study (HRS) cohort.}, journal = {Journals of Gerontology, Series B: Psychological Sciences \& Social Sciences}, volume = {75}, year = {2020}, type = {Journal}, chapter = {1230-1242}, abstract = {

OBJECTIVES: We aimed to determine whether self-assessed single (hearing or visual) and dual sensory (hearing and visual) impairments are associated with cognitive decline and incident possible Cognitive Impairment, No Dementia (CIND) and probable dementia.

METHOD: Data were drawn from the 1996-2014 surveys of the Health and Retirement Study (HRS), involving 19,618 respondents who had no probable dementia and who were aged 50 years or older at the baseline. We used linear mixed models to test the association between self-assessed sensory impairment and cognitive decline followed by a Cox proportional hazard model to estimate the relative risk of incident possible CIND and probable dementia associated with the presence of sensory impairment.

RESULTS: Respondents with self-assessed single and dual sensory impairment performed worse in cognitive tests than those without sensory impairment. The fully adjusted incidence of developing possible CIND was 17\% higher for respondents with hearing impairment than those without hearing impairment. Respondents with visual impairment had 35\% and 25\% higher risk for developing possible CIND and probable dementia, respectively, than those without visual impairment. Respondents with dual sensory impairment at baseline were 38\% and 26\% more likely to develop possible CIND and probable dementia, respectively, than those with no sensory impairment.

DISCUSSION: Self-assessed sensory impairment is independently associated with cognitive decline and incident possible CIND and probable dementia. Further studies are needed to identify the mechanism underlying this association and to determine whether treatment of sensory impairment could ameliorate cognitive decline and delay the onset of dementia among older adults.

}, keywords = {Cognition \& Reasoning, Hearing loss, Risk Factors, Self Report}, issn = {1758-5368}, doi = {10.1093/geronb/gbz043}, author = {Maharani, Asri and Dawes, Piers and James Nazroo and Tampubolon, Gindo and Pendleton, Neil} } @article {11562, title = {Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom.}, journal = {PLoS One}, volume = {13}, year = {2018}, pages = {e0207824}, abstract = {

The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways {\textquoteright}Neuropathic pain signalling in dorsal horn neurons{\textquoteright} and the {\textquoteright}GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells{\textquoteright}, exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms.

}, keywords = {ELSA, Frailty, Gene Ontology, Genome-Wide Association Study, Phenotype}, issn = {1932-6203}, doi = {10.1371/journal.pone.0207824}, author = {Mekli, Krisztina and Stevens, Adam and Alan Marshall and Thalida E. Arpawong and Drystan F. Phillips and Tampubolon, Gindo and Lee, Jinkook and Carol A Prescott and James Nazroo and Pendleton, Neil} } @article {11563, title = {Genome-wide scan of depressive symptomatology in two representative cohorts in the United States and the United Kingdom.}, journal = {Journal of Psychiatric Research}, volume = {100}, year = {2018}, pages = {63-70}, abstract = {

Unlike the diagnosed Major Depressive Disorder, depressive symptomatology in the general population has received less attention in genome-wide association scan (GWAS) studies. Here we report a GWAS study on depressive symptomatology using a discovery-replication design and the following approaches: To improve the robustness of the phenotypic measure, we used longitudinal data and calculated mean scores for at least 3 observations for each individual. To maximize replicability, we used nearly identical genotyping platforms and identically constructed phenotypic measures in both the Discovery and Replication samples. We report one genome-wide significant hit; rs58682566 in the EPG5 gene was associated (p = 3.25E-08) with the mean of the depression symptom in the Discovery sample, without confirmation in the Replication sample. We also report 4 hits exceeding the genome-wide suggestive significance level with nominal replications. Rs11774887, rs4147527 and rs1379328, close to the SAMD12 gene, were associated with the mean depression symptom score (P-values in Discovery sample: 4.58E-06, 7.65E-06 and 7.66E-06; Replication sample: 0.049, 0.029 and 0.030, respectively). Rs13250896, located in an intergenic region, was associated with the mean score of the three somatic items of the depression symptoms score (p = 3.31E-07 and 0.042 for the Discovery and Replication samples). These results were not supported by evidence in the literature. We conclude that despite the strengths of our approach, using robust phenotypic measures and samples that maximize replicability potential, this study does not provide compelling evidence of a single genetic variant{\textquoteright}s significant role in depressive symptomatology.

}, keywords = {depression, ELSA, Genome-Wide Association Study}, issn = {1879-1379}, doi = {10.1016/j.jpsychires.2018.01.016}, author = {Mekli, Krisztina and Drystan F. Phillips and Thalida E. Arpawong and Vanhoutte, Bram and Tampubolon, Gindo and James Nazroo and Lee, Jinkook and Carol A Prescott and Stevens, Adam and Pendleton, Neil} } @article {9741, title = {Longitudinal Relationship Between Hearing Aid Use and Cognitive Function in Older Americans}, journal = {Journal of the American Geriatrics Society}, volume = {66}, year = {2018}, pages = {1130-1136}, abstract = {Objectives: To test whether hearing aid use alters cognitive trajectories in older adults. Design: US population-based longitudinal cohort study Setting: Data were drawn from the Health and Retirement Study (HRS), which measured cognitive performance repeatedly every 2 years over 18 years (1996-2014). Participants: Adults aged 50 and older who who took part in a minimum of 3 waves of the HRS and used hearing aids for the first time between Waves 4 and 11 (N=2,040). Measurements: Cognitive outcomes were based on episodic memory scores determined according to the sum of immediate and delayed recall of 10 words. Results: Hearing aid use was positively associated with episodic memory scores (β=1.53, p<.001). Decline in episodic memory scores was slower after (β=-0.02, p<.001) than before using hearing aids (β=-0.1, p<.001). These results were robust to adjustment for multiple confounders and to attrition, as accounted for using a joint model. Conclusions: Hearing aids may have a mitigating effect on trajectories of cognitive decline in later life. Providing hearing aids or other rehabilitative services for hearing impairment much earlier in the course of hearing impairment may stem the worldwide rise of dementia.}, keywords = {Cognitive Ability, Hearing aids, Hearing loss, Longitudinal data}, doi = {10.1111/jgs.15363}, url = {http://doi.wiley.com/10.1111/jgs.15363http://onlinelibrary.wiley.com/wol1/doi/10.1111/jgs.15363/fullpdfhttps://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111\%2Fjgs.15363}, author = {Maharani, Asri and Dawes, Piers and James Nazroo and Tampubolon, Gindo and Pendleton, Neil} } @article {9583, title = {Visual and hearing impairments are associated with cognitive decline in older people.}, journal = {Age and Ageing}, volume = {47}, year = {2018}, pages = {575-581}, abstract = {

Introduction: highly prevalagent hearing and vision sensory impairments among older people may contribute to the risk of cognitive decline and pathological impairments including dementia. This study aims to determine whether single and dual sensory impairment (hearing and/or vision) are independently associated with cognitive decline among older adults and to describe cognitive trajectories according to their impairment pattern.

Material and methods: we used data from totals of 13,123, 11,417 and 21,265 respondents aged 50+ at baseline from the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE), respectively. We performed growth curve analysis to identify cognitive trajectories, and a joint model was used to deal with attrition problems in longitudinal ageing surveys.

Results: respondents with a single sensory impairment had lower episodic memory score than those without sensory impairment in HRS (β = -0.15, P < 0.001), ELSA (β= -0.14, P< 0.001) and SHARE (β= -0.26, P < 0.001). The analysis further shows that older adults with dual sensory impairment in HRS (β= -0.25, P < 0.001), ELSA (β= -0.35, P< 0.001) and SHARE (β= -0.68, P < 0.001) remembered fewer words compared with those with no sensory impairment. The stronger associations between sensory impairment and lower episodic memory levels were found in the joint model which accounted for attrition.

Conclusions: hearing and/or vision impairments are a marker for the risk of cognitive decline that could inform preventative interventions to maximise cognitive health and longevity. Further studies are needed to investigate how sensory markers could inform strategies to improve cognitive ageing.

}, keywords = {Cognitive Ability, Cross-National, GWAS, Hearing loss, Visual function}, issn = {1468-2834}, doi = {10.1093/ageing/afy061}, author = {Maharani, Asri and Dawes, Piers and James Nazroo and Tampubolon, Gindo and Pendleton, Neil} }