Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure.

OBJECTIVE: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization. RESEARCH DESIGN AND METHODS: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms and signs of DSPN were assessed in 1,792 participants at DPPOS year 17. Multivariable logistic regression models were used to evaluate DSPN associations with treatment group, diabetes status/duration, and cumulative glycemic exposure. RESULTS: At 21 years after DPP randomization, 66% of subjects had diabetes. DSPN prevalence did not differ by initial DPP treatment assignment (ILS 21.5%, metformin 21.5%, and placebo 21.9%). There was a significant interaction between treatment assignment to ILS and age (P < 0.05) on DSPN. At DPPOS year 17, the odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals. DSPN prevalence was slightly lower for those at risk for diabetes (19.6%) versus those with diabetes (22.7%) and was associated with longer diabetes duration and time-weighted HbA1c (P values <0.001). CONCLUSIONS: The likelihood of DSPN was similar across DPP treatment groups but higher for those with diabetes, longer diabetes duration, and higher cumulative glycemic exposure. ILS may have long-term benefits on DSPN for older adults.

Positive thinking about negative studies.

The non-reporting of negative studies results in a scientific record that is incomplete, one-sided and misleading. The consequences of this range from inappropriate initiation of further studies that might put participants at unnecessary risk to treatment guidelines that may be in error, thus compromising day-to-day clinical practice.

Deep Learning and Geriatric Mental Health.

The goal of this overview is to help clinicians develop basic proficiency with the terminology of deep learning and understand its fundamentals and early applications. We describe what machine learning and deep learning represent and explain the underlying data science principles. We also review current promising applications and identify ethical issues that bear consideration. Deep Learning is a new type of machine learning that is remarkably good at finding patterns in data, and in some cases generating realistic new data. We provide insights into how deep learning works and discuss its relevance to geriatric psychiatry.

Effect of pioglitazone on vascular events in post-stroke cognitive impairment: Post hoc analysis of the IRIS trial.

BACKGROUND: In stroke patients with insulin resistance (IR), post-stroke cognitive impairment (PSCI) is associated with higher risk of recurrent stroke, but the effect of pioglitazone on that risk has not been explored. The goal of this study was to compare the secondary stroke prevention effect of pioglitazone against placebo in patients with versus without PSCI. METHODS: We studied patients enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial with a post-stroke modified Mini-Mental State Examination (3MS) cognitive assessment (mean time of assessment: 79 days post-stroke). We considered a baseline score of ⩽ 88 on the 3MS to indicate global PSCI, and domain-specific summary scores in the lowest quartile to indicate attention, language, memory, orientation, and visuospatial impairments. RESULTS: In n = 3338 patients with IR, the effect of pioglitazone versus placebo on secondary stroke significantly differed by initial post-stroke global (interaction p = 0.0127) and memory impairment status (interaction p = 0.0003). Hazard ratios (HRs) were time-dependent such that, among those with either global or memory impairment, pioglitazone has an increasingly stronger protective effect at later timepoints. There was no statistically significant effect of pioglitazone among those without either global or memory impairment. The effect of pioglitazone versus placebo on myocardial infarction (MI) also significantly differed by global impairment status (interaction p = 0.030). Pioglitazone was protective among those with global impairment (HR = 0.23 [95% CI: 0.08, 0.71]) but not among those without (HR = 0.88 [95% CI: 0.59, 1.31]). CONCLUSION: These data indicate that pioglitazone treatment may be more effective at reducing risk of recurrent stroke and MI in stroke patients with PSCI. Simple cognitive testing 2-3 months post-stroke may identify patients for whom treatment would be most beneficial.

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

OBJECTIVE: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. METHODS: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. RESULTS: Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase. CONCLUSION: This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

Post-stroke cognitive impairment and the risk of stroke recurrence and death in patients with insulin resistance.

OBJECTIVE: Post-stroke cognitive impairment (PSCI) is associated with etiology, severity, and functional outcome of stroke. The risks of recurrent stroke and death in patients with PSCI and insulin resistance (IR) is unknown. The goal of this study was to determine whether global and domain-specific cognitive impairment after stroke in patients with IR was associated with recurrent stroke and death. MATERIALS AND METHODS: We studied patients with recent stroke or transient ischemic attack (TIA) and IR with a baseline Modified Mini-Mental State Examination (3MS) cognitive exam at median of 79 days after stroke. We considered a baseline score of ≤ 88 on the 3MS to indicate global cognitive impairment, and domain-specific summary scores in the lowest quartile to indicate language, attention, orientation, memory and visuospatial impairments. The primary endpoint was fatal or non-fatal recurrent stroke, and the secondary endpoints were all-cause mortality, and fatal or non-fatal myocardial infarction (MI). RESULTS: Among studied n = 3,338 patients 13.6% had global cognitive impairment. During the median 4.96 years of follow-up, 7.4% patients experienced recurrent stroke, 3.5% MI, and 7.3% died. In the fully adjusted model, impairment in language (HR 1.35; 95% CI 1.01-1.81) and orientation (HR 1.41; 95% CI: 1.06-1.87) were associated with a higher risk of recurrent stroke, while attention impairment was associated with all-cause mortality (HR 1.34; 95% CI: 1.01-1.78). DISCUSSION/CONCLUSION: In patients with recent stroke/TIA and IR, post-stroke language and orientation impairments independently predicted recurrent stroke, while attention deficit was associated with increased risk of all-cause mortality.

Elucidating age and sex-dependent association between frontal EEG asymmetry and depression: An application of multiple imputation in functional regression.

Frontal power asymmetry (FA), a measure of brain function derived from electroencephalography, is a potential biomarker for major depressive disorder (MDD). Though FA is functional in nature, it is typically reduced to a scalar value prior to analysis, possibly obscuring its relationship with MDD and leading to a number of studies that have provided contradictory results. To overcome this issue, we sought to fit a functional regression model to characterize the association between FA and MDD status, adjusting for age, sex, cognitive ability, and handedness using data from a large clinical study that included both MDD and healthy control (HC) subjects. Since nearly 40% of the observations are missing data on either FA or cognitive ability, we propose an extension of multiple imputation (MI) by chained equations that allows for the imputation of both scalar and functional data. We also propose an extension of Rubin's Rules for conducting valid inference in this setting. The proposed methods are evaluated in a simulation and applied to our FA data. For our FA data, a pooled analysis from the imputed data sets yielded similar results to those of the complete case analysis. We found that, among young females, HCs tended to have higher FA over the θ, α, and ß frequency bands, but that the difference between HC and MDD subjects diminishes and ultimately reverses with age. For males, HCs tended to have higher FA in the ß frequency band, regardless of age. Young male HCs had higher FA in the θ and α bands, but this difference diminishes with increasing age in the α band and ultimately reverses with increasing age in the θ band.

Facing Our Fears: The Impact of a 4-Day Training Intervention to Reduce Negative Perspectives on Sexual and Gender Minorities among Religious Leaders in Kenya.

This study evaluated short- and long-term impact of a 4-day training intervention to reduce negative perspectives of religious leaders in Kenya on sexual and gender minorities, adopting a one-group pretest-posttest-follow-up design. Religious leaders' perspectives play an important role in maintaining the negative status quo for sexual and gender minorities, especially in Africa, where religion's impact is ubiquitous and holding negative attitudes against these populations is perceived as an expression of doctrinal orthodoxy. The training, developed by a community-based organization, employs a variety of strategies, including education, storytelling, and in-person contact. Data were collected directly before and after the training, and at 3- to 4-months follow-up. After the training, acceptance of lesbian women and gay men and gender diversity had increased, while attitudes toward gender and sexual minorities became more positive. Interaction effect analysis showed that compared to women, men changed more, as did those who scored higher on religious fundamentalism. Changes in attitudes were maintained at follow-up (three to four months). Although it is not clear whether the training had an impact on the religious leaders' interactions with members of their congregation, these findings suggest that intensive trainings may promote positive changes in their perspective on gender and sexual minorities.

Frailty and Depression in Late Life: A High-Risk Comorbidity With Distinctive Clinical Presentation and Poor Antidepressant Response.

BACKGROUND: To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. METHODS: An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score <10), and frailty (non/intermediate frail [0-2 deficits] vs frail [≥3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories. RESULTS: A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10). CONCLUSIONS: Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.

Extracting scalar measures from functional data with applications to placebo response.

In controlled and observational studies, outcome measures are often observed longitudinally. Such data are difficult to compare among units directly because there is no natural ordering of curves. This is relevant not only in clinical trials, where typically the goal is to evaluate the relative efficacy of treatments on average, but also in the growing and increasingly important area of personalized medicine, where treatment decisions are optimized with respect to a relevant patient outcome. In personalized medicine, there are no methods for optimizing treatment decision rules using longitudinal outcomes, e.g., symptom trajectories, because of the lack of a natural ordering of curves. A typical practice is to summarize the longitudinal response by a scalar outcome that can then be compared across patients, treatments, etc. We describe some of the summaries that are in common use, especially in clinical trials. We consider a general summary measure (weighted average tangent slope) with weights that can be chosen to optimize specific inference depending on the application. We illustrate the methodology on a study of depression treatment, in which it is difficult to separate placebo effects from the specific effects of the antidepressant. We argue that this approach provides a better summary for estimating the benefits of an active treatment than traditional non-weighted averages.

Educational Value of Endoscopic Versus Microscopic Ear Surgery.

OBJECTIVE: To compare the educational value of endoscopic ear surgery versus microscopic ear surgery among medical students. METHODS: Medical students anonymously completed a cross-sectional survey immediately after observing endoscopic or microscopic ear surgery. A Likert scale (1 = worst, 5 = best) was used to analyze variables across 3 domains including: (1) area of interest visibility, (2) optical quality, (3) education and understanding. The Mann-Whitney U-test and multivariable linear regression were used to compare mean scores of individual items and domain means between endoscopic and microscopic groups. RESULTS: Forty-four surveys were analyzed (20 endoscopic and 24 microscopic ear surgeries). Across domains, the endoscope was superior to the microscope (adjusted P < .05) for visibility of the area of interest (mean ± SD: 4.74 ± 0.26 vs 4.28 ± 0.50), optical quality (4.78 ± 0.38 vs 4.28 ± 0.64), and education and understanding (4.70 ± 0.47 vs 4.13 ± 0.61). In multivariable linear regression, the mean domain score for visibility of the area of interest was 1.23 (95% CI = 0.56, 1.90; adjusted P < .01) points higher for the endoscopic group, compared to the microscopic group, adjusting for surgeon, procedure, and student type. The mean domain score for education and understanding was 1.19 (95% CI = 0.49. 1.90; adjusted P < 0.01) points higher for the endoscopic group, compared to the microscopic group, adjusting for the same confounders. CONCLUSIONS: Among medical students, endoscopic ear surgery was superior to microscopic ear surgery for several visual quality indicators and perceived educational benefit. These findings have implications for medical student education and surgical training.

Development of novel measures for Alzheimer's disease prevention trials (NoMAD).

INTRODUCTION: Assessment of cognition and everyday function is essential in clinical trials for Alzheimer's disease (AD). Two novel measures of cognition (No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS)) were designed to have robust psychometric properties and reduced practice and ceiling effects. This study aims to evaluate if the NPE and CFAS demonstrate stronger psychometric properties and reduced practice effects compared with established measures, including the Preclinical Alzheimer Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Functional Activities Questionnaire (FAQ). METHODS: This parallel group, four-site study will randomize 320 cognitively intact adults aged 60 to 85 years to novel or well-established measures of cognition and function. All participants will receive assessments at baseline (week 0), 3-months, and 12-months, as well as a brain MRI scan and Apolipoprotein E genetic test at study entry. Analyses will determine psychometric properties of the NPE and CFAS, compare the sensitivity of measures to AD risk markers, and identify cognitive domains within the NPE. DISCUSSION: Practice effects have been a major limitation of Alzheimer's disease clinical trials that typically assess cognitive changes over serial assessments. Detection of functional impairment in cognitively normal individuals with biomarkers for Alzheimer's disease requires instruments sensitive to very subtle functional changes. This study is intended to support the validation of two new composite measures, the NPE battery and the CFAS, which may advance clinical testing of interventions for individuals across the spectrum of early stage Alzheimer's disease. TRIAL REGISTRATION: NCT03900273.

Measures of variability and precision in statistics: appreciating, untangling and applying concepts.

This reflection presents a discussion of some common measures of variability and how they are appropriately used in descriptive and inferential statistical analyses. We argue that confidence intervals (CIs), which incorporate these measures, serve as tools to assess both clinical and statistical significance.

The Missing Link(age): Multilevel Contributors to Service Uptake Failure Among Youths on Community Justice Supervision.

OBJECTIVES: Youths in the juvenile justice system often do not access needed behavioral health services. The behavioral health services cascade model was used to examine rates of substance use screening, identification of substance use treatment needs, and referral to and initiation of treatment among youths undergoing juvenile justice system intake and to identify when treatment access is most challenged. Characteristics associated with identification of behavioral health needs and linkage to community services were also examined. METHODS: Data were drawn from administrative records of 33 community justice agencies in seven states participating in Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System, funded by the National Institute on Drug Abuse (N=8,307 youths). Contributions of youth, staff, agency, and county characteristics to identification of behavioral health needs and linkage to community services were examined. RESULTS: More than 70% (5,942 of 8,307) of youths were screened for substance use problems, and more than half needed treatment. Among those in need, only about one-fifth were referred to treatment, and among those referred, 67.5% initiated treatment. Overall, <10% of youths with identified needs initiated services. Multivariable multilevel regression analyses revealed several contributors to service-related outcomes, with youths' level of supervision being among the strongest predictors of treatment referral. CONCLUSIONS: Community justice agencies appear to follow an approach that focuses identification and linkage practices on concerns other than youths' behavioral health needs, although such needs contribute to reoffending. Local agencies should coordinate efforts to support interagency communication in the referral and cross-system linkage process.

Frailty Worsens Antidepressant Treatment Outcomes in Late Life Depression.

OBJECTIVE: To investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression (LLD). METHODS: Data were evaluated from 100 individuals over age 60 years (34 men, 66 women) with a depressive diagnosis, who were assessed for frailty at baseline (characteristics include gait speed, grip strength, activity levels, fatigue, and weight loss) and enrolled in an 8-week trial of antidepressant medication followed by 10 months of open-treatment. RESULTS: Frail individuals (n = 49 with ≥3 deficits in frailty characteristics) did not differ at baseline from the non/intermediate frail (n = 51 with 0-2 deficits) on demographic, medical comorbidity, cognitive, or depression variables. On average, frail individuals experienced 2.82 fewer Hamilton Rating Scale for Depression (HRSD) points of improvement (t = 2.12, df 89, p = 0.037) than the non/intermediate frail over acute treatment, with this difference persisting over 10 months of open-treatment. Weak grip strength and low physical activity levels were each associated with decreased HRSD improvement, and lower response and remission rates over the course of the study. Despite their poorer outcomes, frail individuals received more antidepressant medication trials than the non/intermediate frail. CONCLUSION: Adults with LLD and frailty have an attenuated response to antidepressant medication and a greater degree of disability compared to non/intermediate frail individuals. This disability and attenuated response remain even after receiving a greater number of antidepressant medication trials. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population.

Trends in Relative Incidence and Prevalence of Dementia Across Non-Hispanic Black and White Individuals in the United States, 2000-2016.

Importance: In the US, dementia risk is higher in non-Hispanic Black individuals than in non-Hispanic White individuals. To evaluate progress toward reducing such disparities, tracking secular trends in racial disparities in dementia prevalence is essential. Objective: To examine whether relative racial disparities in dementia prevalence or incidence have changed in the US from 2000 to 2016. Design, Settings, and Participants: The Health and Retirement Study (HRS) is a nationally representative study of adults 50 years or older. New participants are recruited every 6 years, and study visits occur biennially. Approximately 17 000 to 22 000 respondents have been surveyed at each wave since 2000, achieving response rates of 81% to 89%. Data for this cohort study were obtained from non-Hispanic White and non-Hispanic Black participants aged 70 years and older from the 2000 to 2016 waves. For analyses of secular trends in racial disparities in dementia prevalence, each HRS wave was considered separately (range of participants meeting eligibility criteria in each wave, 6322-7579). For analyses of secular trends in racial disparities in dementia incidence, 7 subcohorts were created (range of participants meeting eligibility criteria in each subcohort, 5322-5961) following up people without dementia for 4 years from subcohort baseline visits in 2000, 2002, 2004, 2006, 2008, 2010, and 2012. Data were analyzed from October 2019 to August 2020. Exposures: Race based on self-response to closed-ended survey questions. Main Outcomes and Measures: Dementia status was determined using 3 algorithms with similar sensitivity and specificity across non-Hispanic White and Black participants. Disparities were characterized using ratio measures. Results: In this study, the mean age and percentage of male participants eligible for inclusion in analyses of racial disparities in dementia prevalence increased over time among non-Hispanic White participants (from 78.2 years and 40% in 2000 to 78.7 years and 44% in 2016) but remained steady in non-Hispanic Black participants during the same period (from 78.0 years and 37% in 2000 to 77.9 years and 38% in 2016). Prevalence ratios comparing Black and White participants ranged from approximately 1.5 to 1.9 across algorithms and years, whereas hazard ratios ranged from approximately 1.4 to 1.8. Although results suggest stable or declining dementia risk overall, there was no evidence suggesting change in relative racial disparities in dementia prevalence or incidence during follow-up. Conclusions and Relevance: This study did not find evidence to suggest that the ratio of dementia risk across Black and White individuals changed in the US between 2000 and 2016. Additional efforts to identify and mitigate the source of these disparities is warranted.

Implications of the Use of Algorithmic Diagnoses or Medicare Claims to Ascertain Dementia.

INTRODUCTION: Formal dementia ascertainment with research criteria is resource-intensive, prompting the growing use of alternative approaches. Our objective was to illustrate the potential bias and implications for study conclusions introduced through the use of alternate dementia ascertainment approaches. METHODS: We compared dementia prevalence and risk factor associations obtained using criterion-standard dementia diagnoses to those obtained using algorithmic or Medicare-based dementia ascertainment in participants of the baseline visit of the Aging, Demographics, and Memory Study (ADAMS), a Health and Retirement Study (HRS) sub-study. RESULTS: Estimates of dementia prevalence derived using algorithmic or Medicare-based ascertainment differ substantially from those obtained using criterion-standard ascertainment. Use of algorithmic or Medicare-based dementia ascertainment can, but does not always, lead to risk factor associations that substantially differ from those obtained using criterion-standard ascertainment. DISCUSSION/CONCLUSIONS: Absolute estimates of dementia prevalence should rely on samples with formal dementia ascertainment. The use of multiple algorithms is recommended for risk factor studies when formal dementia ascertainment is not available.

Subclinical Hearing Loss is Associated With Depressive Symptoms.

OBJECTIVE: To assess whether the relationship between hearing and depressive symptoms is present among older adults classified as normal hearing (≤25 dB). DESIGN: Cross-sectional epidemiologic study (Hispanic Community Health Study). SETTING: US multicentered. PARTICIPANTS: Adults ≥50 years old (n = 5,499) with normal hearing or hearing loss (HL). MEASUREMENTS: The primary exposure was hearing, defined continuously by the 4-frequency pure-tone average threshold (dB) on audiometry. Hearing was additionally categorized into normal hearing (≤25 dB) and HL (>25 dB). The main outcome was depressive symptoms, measured with the Center for Epidemiologic Studies Depression Scale-10 (CESD-10). Depressive symptoms were defined both continuously and binarily (where CESD-10 ≥10 was categorized as clinically significant depressive symptoms). Multivariable linear, logistic, and generalized additive modeling (GAM) regressions were performed. RESULTS: Among those with normal hearing, the CESD-10 score increased by 1.04 points (95% confidence interval [CI]: 0.70, 1.37) for every 10 dB decrease in hearing, adjusting for age, gender, education, cardiovascular disease, and hearing aid use. Among those with HL, the CESD-10 score increased by 0.62 points (95% CI: 0.23, 1.01) for every 10 dB decrease in hearing, adjusting for the same confounders. Similar findings were noted when the outcome was clinically significant depressive symptoms (adjusted odds ratio: 1.28 [1.14, 1.44] in normal hearing versus 1.26 [1.11, 1.44] in HL). In certain sensitivity analyses, the relationship between hearing and depressive symptoms was significantly stronger among those with normal hearing than in those with HL. CONCLUSION: The relationship between hearing and clinically significant depressive symptoms is present among older adults with normal hearing (<25 dB). We introduce the term subclinical HL as imperfect hearing that is classically defined as normal (1-25 dB). The relationship between hearing and late life depressive symptoms may be more sensitive than previously recognized.

Audiometric Age-Related Hearing Loss and Cognition in the Hispanic Community Health Study.

BACKGROUND: Age-related hearing loss (HL), a common and treatable condition, has been associated with other age-related conditions. Late life cognitive impairment is a major public health concern that is rarely treatable. Studies examining the relationship between HL and cognition have been limited by non-Hispanic cohorts, small samples, or limited confounding control. We overcome these limitations in a large Hispanic cohort. METHODS: This was a multisite cross-sectional study of 5,277 subjects at least 50 years old (Hispanic Community Health Study, HCHS). The main exposure was audiometric HL. The main outcome measure was neurocognitive performance ascertained by the Digit Symbol Substitution Test (DSST), Word Frequency Test, Spanish-English Verbal Learning Test (SEVLT), and Six-Item Screener. RESULTS: The mean age was 58.4 years (SD = 6.2). A 20-dB (equivalent to a one-category worsening) increase in HL was associated with a -1.53 (95% CI, -2.11, -0.94) raw score point difference in the DSST, adjusting for demographics, hearing aid use, and cardiovascular disease. Similarly, a 20-dB increase in HL was associated with a -0.86 (-1.23, -0.49) point difference on the Word Frequency Test, -0.76 (-1.04, -0.47) on the SEVLT 3 trials, -0.45 (-0.60, -0.29) on the SELVT recall, and -0.07 (-0.12, -0.02) on the Six-Item Screener. CONCLUSIONS: In the largest study of formal, audiometric HL and cognition to date, HL was independently associated with worse performance in a range of neurocognitive measures. Because HL is common and potentially treatable, it should be investigated as a modifiable risk factor for neurocognitive decline and dementia.

An imaging-based risk calculator for prediction of conversion to psychosis in clinical high-risk individuals using glutamate 1H MRS.

Risk calculators for prediction of conversion of Clinical High-Risk (CHR) individuals to syndromal psychosis have recently been developed and have generated considerable clinical use and research interest. Predictor variables in these calculators have been clinical rather than biological, and our goal was to incorporate a neurochemical imaging measure into this framework and assess its impact on prediction. We combined striatal glutamate 1H MRS data with the SIPS symptoms identified by the Columbia Risk Calculator as having the greatest predictive value in order to develop an imaging-based risk calculator for conversion to psychosis. We evaluated the calculator in 19 CHR individuals, 7 (36.84%) of whom converted to syndromal psychosis during the 2-year follow up. The receiver operating characteristic (ROC) curve for the logistic model including only striatal glutamate and visual perceptual abnormalities showed an AUC = 0.869 (95% CI = [0.667, 1.000]) and AUCoa = 0.823, with sensitivity of 0.714, specificity of 0.917, positive predictive value of 0.833, and negative predictive value of 0.846. These results represent modest improvements over each of the individual ROC curves based on either striatal glutamate or visual perceptual abnormalities alone. The preliminary model building and evaluation presented here in a small CHR sample suggests that the approach of incorporating predictive imaging measures into risk classification is not only feasible but offers the potential of enhancing risk assessment.