Bodily pain in survivors of acute respiratory distress syndrome: A 1-year longitudinal follow-up study.

PURPOSE: Acute respiratory distress syndrome (ARDS) survivors frequently experience bodily pain during recovery after the intensive care unit. Longitudinal course, risk factors and associations with physical and neuropsychological health is lacking. METHODS: We collected self-reported pain using the Short Form-36 Bodily Pain (SF-36 BP) scale, normalized for sex and age (range: 0-100; higher score = less pain), along with physical and mental health measures in a multi-center, prospective cohort of 826 ARDS survivors at 6- and 12-month follow-up. We examined baseline and ICU variables' associations with pain via separate unadjusted regression models. RESULTS: Pain prevalence (SF-36 BP ≤40) was 45% and 42% at 6 and 12 months, respectively. Among 706 patients with both 6- and 12-month data, 34% reported pain at both timepoints. Pre-ARDS employment was associated with less pain at 6-months (mean difference (standard error), 5.7 (0.9), p < 0.001) and 12-months (6.3 (0.9), p < 0.001); smoking history was associated with greater pain (-5.0 (0.9), p < 0.001, and - 5.4 (1.0), p < 0.001, respectively). In-ICU opioid use was associated with greater pain (-6.3 (2.7), p = 0.02, and - 7.3 (2.8), p = 0.01, respectively). At 6 months, 174 (22%) patients reported co-occurring pain, depression and anxiety, and 227 (33%) reported co-occurring pain and impaired physical function. CONCLUSION: Nearly half of ARDS survivors reported bodily pain at 6- and 12-month follow-up; one-third reported pain at both time points. Pre-ARDS unemployment, smoking history, and in-ICU opioid use may identify patients who report greater pain during recovery. Given its frequent co-occurrence, clinicians should manage both physical and neuropsychological issues when pain is reported.

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients.

OBJECTIVES: While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium. METHODS: Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study "A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aß) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)181. RESULTS: For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02-1.25). Both CSF Aß42/t-tau (ß = -1.52, 95%CI = -2.1 to -0.05) and Aß42/p-tau181 (ß = -0.29, 95%CI = -0.48 to -0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers. CONCLUSIONS: In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome.

Psychotropic Medication and Cognitive, Functional, and Neuropsychiatric Outcomes in Alzheimer's Disease (AD).

BACKGROUND/OBJECTIVES: There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort. DESIGN: Longitudinal observational study. SETTING: National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers. PARTICIPANTS: 8,034 participants with AD dementia. MEASUREMENTS: Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and Neuropsychiatric Inventory Questionnaire (NPI-Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non-SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest-matched PS. The effect of medication treatment was assessed using linear mixed-effects models. RESULTS: Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR-SB 5.5 (3.4), and NPI-Q Total 4.5 (4.4). Mean duration of follow-up was 2.9-3.3 years depending on medication class. Non-SSRI antidepressant use was associated with better CDR-SB (2-year difference in change-DIC: -0.38 [-0.61, -0.15], P = .001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: -0.91 [-1.54, -0.28] P = .005) and CDR-SB scores (DIC: 0.50 [0.14, 0.86], P = .006). Notably, no drug class was associated with better NPI-Q scores. CONCLUSIONS: Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms.

Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer's disease dementia.

OBJECTIVES: To examine trajectories of depression and apathy over a 5-year follow-up period in (prodromal) Alzheimer's disease (AD), and to relate these trajectories to AD biomarkers. METHODS: The trajectories of depression and apathy (measured with the Neuropsychiatric Inventory or its questionnaire) were separately modeled using growth mixture models for two cohorts (National Alzheimer's Coordinating Center, NACC, n = 22 760 and Alzheimer's Disease Neuroimaging Initiative, ADNI, n = 1 733). The trajectories in ADNI were associated with baseline CSF AD biomarkers (Aß42, t-tau, and p-tau) using bias-corrected multinomial logistic regression. RESULTS: Multiple classes were identified, with the largest classes having no symptoms over time. Lower Aß42 and higher tau (ie, more AD pathology) was associated with increased probability of depression and apathy over time, compared to classes without symptoms. Lower Aß42 (but not tau) was associated with a steep increase of apathy, whereas higher tau (but not Aß42 ) was associated with a steep decrease of apathy. DISCUSSION: The trajectories of depression and apathy in individuals on the AD spectrum are associated with AD biomarkers.

Neurotransmitters and Neurometabolites in Late-Life Depression: A Preliminary Magnetic Resonance Spectroscopy Study at 7T.

BACKGROUND: Magnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD). METHODS: Nine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T 1H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only). Spectra were acquired from two brain regions implicated in both depressive symptoms and neuropsychological deficits in LLD, the anterior (ACC) and posterior cingulate (PCC). Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr) using linear-combination modeling. RESULTS: Baseline Glu/tCr levels were not significantly different between groups. Decreased Glu/tCr levels after Citalopram treatment were observed in a subset of LLD patients. Exploratory analyses showed that LLD patients had lower NAA levels in the PCC relative to controls. Higher levels of ml in the LLD patients relative to the controls and decreases after Citalopram treatment had large effect sizes but were not statistically significant. Further, decreases in PCC Glu/tCr and increases in ACC GSH/tCr were associated with improvement in depressive symptoms. LIMITATIONS: Sample size. CONCLUSIONS: These preliminary results suggest a role of neurochemicals and neurometabolites in the neurobiology of LLD and antidepressant treatment response.

Fatigue Symptoms During the First Year Following ARDS.

BACKGROUND: Fatigue is commonly reported by ARDS survivors, but empirical data are scarce. RESEARCH QUESTION: This study evaluated fatigue prevalence and associated variables in a prospective study of ARDS survivors. STUDY DESIGN AND METHODS: This analysis is part of the ARDSNet Long-Term Outcomes Study (ALTOS) conducted at 38 US hospitals. Using age- and sex-adjusted, time-averaged random effects regression models, we evaluated associations between the validated Functional Assessment of Chronic Illness Therapy-Fatigue Scale with patient and critical illness variables, and with physical, cognitive, and mental health status at 6 and 12 months following ARDS. RESULTS: Among ARDS survivors, 501 of 711 (70%) and 436 of 659 (66%) reported clinically significant symptoms of fatigue at 6 and 12 months, respectively, with 41% and 28% reporting clinically important improvement and worsening (n = 638). At 6 months, the prevalence of fatigue (70%) was greater than that of impaired physical functioning (50%), anxiety (42%), and depression (36%); 46% reported both impaired physical function and fatigue, and 27% reported co-existing anxiety, depression, and fatigue. Fatigue was less severe in men and in those employed prior to ARDS. Critical illness variables (eg, illness severity, length of stay) had little association with fatigue symptoms. Worse physical, cognitive, and mental health symptoms were associated with greater fatigue at both the 6- and 12-month follow-up. INTERPRETATION: During the first year following ARDS, more than two-thirds of survivors reported clinically significant fatigue symptoms. Due to frequent co-occurrence, clinicians should evaluate and manage survivors' physical, cognitive, and mental health status when fatigue is endorsed.

Correction to: Screening for posttraumatic stress disorder in ARDS survivors: validation of the impact of event Scale-6 (IES-6).

In the publication of this article [1], there is an error in the Abstract. This has now been included in this correction article.

Prevalence and Improvement of Caine-Positive Wernicke-Korsakoff Syndrome in Psychiatric Inpatient Admissions.

BACKGROUND: Wernicke-Korsakoff Syndrome (WKS) resulting from thiamine deficiency is classically defined as including encephalopathy, ataxia, and ophthalmoplegia. Only 16% of autopsy-confirmed patients with WKS exhibit all three signs. Caine-positive WKS criteria include two or more of the following: nutritional deficiency, delirium or mild memory impairment, cerebellar dysfunction/ataxia, and oculomotor abnormalities. OBJECTIVE: We describe Caine-positive WKS prevalence among psychiatric inpatients and compare pretreatment-versus-posttreatment neurocognitive improvement to an unaffected group. METHODS: This 6-month quality-improvement evaluation included two-stage screening for Caine-positive WKS, administering high-dose intravenous thiamine (day 1: 1200 mg; days 2-4: 200 mg) with reexamination on day 5. We used descriptive statistics and fitted random effects models to examine rate-of-change differences in pre-/posttreatment Montreal Cognitive Assessment (MoCA), delayed 5-item recall, and gait/coordination scores between treated Caine-positive patients with WKS and untreated Caine-negative patients. RESULTS: Of 262 patients, 32 (12%) had Caine-positive WKS; 17 (53%) used alcohol currently. Treated Caine-positive WKS (n = 26) versus Caine-negative comparison (n = 34) before and after treatment observed a mean change (standard deviation) in the MoCA score of 3.6 (2.5) versus 1.8 (2.5) (P < 0.01); 5-item recall: 1.8 (1.4) versus 0.5 (1.4) (P < 0.001); gait/coordination scores: -0.6 (1.2) versus -0.1 (0.6) (P < 0.001). Oculomotor abnormalities were infrequent (n = 4 in Caine-positive WKS, n = 2 in Caine-negative comparison groups). CONCLUSIONS: Caine-positive WKS prevalence among psychiatric inpatients was 12%; only half used alcohol. Patients treated with high-dose thiamine demonstrated clinically significant neurocognitive improvement.

Survival time tool to guide care planning in people with dementia.

OBJECTIVE: To develop survival prediction tables to inform physicians and patients about survival probabilities after the diagnosis of dementia and to determine whether survival after dementia diagnosis can be predicted with good accuracy. METHODS: We conducted a nationwide registry-linkage study including 829 health centers, i.e., all memory clinics and ≈75% of primary care facilities, across Sweden. Data including cognitive function from 50,076 people with incident dementia diagnoses ≥65 years of age and registered with the Swedish Dementia Register in 2007 to 2015 were used, with a maximum follow-up of 9.7 years for survival until 2016. Sociodemographic factors, comorbidity burden, medication use, and dates of death were obtained from nationwide registries. Cox proportional hazards regression models were used to create tables depicting 3-year survival probabilities for different risk factor profiles. RESULTS: By August 2016, 20,828 (41.6%) patients in our cohort had died. Median survival time from diagnosis of dementia was 5.1 (interquartile range 2.9-8.0) years for women and 4.3 (interquartile range 2.3-7.0) years for men. Predictors of mortality were higher age, male sex, increased comorbidity burden and lower cognitive function at diagnosis, a diagnosis of non-Alzheimer dementia, living alone, and using more medications. The developed prediction tables yielded c indexes of 0.70 (95% confidence interval [CI] 0.69-0.71) to 0.72 (95% CI 0.71-0.73) and showed good calibration. CONCLUSIONS: Three-year survival after dementia diagnosis can be predicted with good accuracy. The survival prediction tables developed in this study may aid clinicians and patients in shared decision-making and advance care planning.

Trajectories of neuropsychiatric symptoms over time in healthy volunteers and risk of MCI and dementia.

OBJECTIVES: To identify subtypes of neuropsychiatric symptom (NPS) course among cognitively normal individuals and to assess the association between these subtypes and hazard of later mild cognitive impairment (MCI) or dementia diagnosis. METHODS: We modeled neuropsychiatric inventory questionnaire (NPI-Q) scores from 4184 volunteers over approximately 4 years using growth mixture models, generating latent classes of trajectory. We then fit Cox proportional hazard models to determine if membership in trajectory classes was associated with increased hazard of diagnosis of MCI or dementia. RESULTS: We identified four trajectory classes: the majority of the sample (65%) would be expected to belong to a class with consistently low or zero NPS. The next most prevalent class, (16%) showed a decrease over time in NPI-Q total score but, compared with the majority class had an almost threefold increase in hazard of MCI or dementia (HR: 2.92; 95% CI: 1.82-4.68). Another class (14%) showed an increase in NPS over time and was also associated with greater hazard of MCI or dementia (HR: 3.96; CI: 2.61-6.03). The smallest class (5%) had high and fluctuating NPI-Q total scores and had the greatest hazard (HR: 4.57; CI: 2.72-7.63). CONCLUSION: We have demonstrated that it is possible to identify meaningful groups of NPS trajectories and that trajectory of NPS can convey information beyond a single cross-sectional measure. While even those whose NPS improved were at increased hazard of MCI or dementia, hazard increased as a function of the severity of the NPS trajectory.

Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6).

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are common in acute respiratory distress syndrome (ARDS) survivors. Brief screening instruments are needed for clinical and research purposes. We evaluated internal consistency, external construct, and criterion validity of the Impact of Event Scale-6 (IES-6; 6 items) compared to the original Impact of Event Scale-Revised (IES-R; 22 items) and to the Clinician Administered PTSD Scale (CAPS) reference standard evaluation in ARDS survivors. METHODS: This study is a secondary analysis from two independent multi-site, prospective studies of ARDS survivors. Measures of internal consistency, and external construct and criterion validity were evaluated. RESULTS: A total of 1001 ARDS survivors (51% female, 76% white, mean (SD) age 49 (14) years) were evaluated. The IES-6 demonstrated internal consistency over multiple time points up to 5 years after ARDS (Cronbach's alpha = 0.86 to 0.91) and high correlation with the IES-R (0.96; 95% confidence interval (CI): 0.94 to 0.97). The IES-6 demonstrated stronger correlations with related constructs (e.g., anxiety and depression; |r| = 0.32 to 0.52) and weaker correlations with unrelated constructs (e.g., physical function and healthcare utilization measures (|r| = 0.02 to 0.27). Criterion validity evaluation with the CAPS diagnosis of PTSD in a subsample of 60 participants yielded an area under receiver operating characteristic curve (95% CI) of 0.93 (0.86, 1.00), with an IES-6 cutoff score of 1.75 yielding 0.88 sensitivity and 0.85 specificity. CONCLUSIONS: The IES-6 is reliable and valid for screening for PTSD in ARDS survivors and may be useful in clinical and research settings.

Cognitive and functional progression of dementia in two longitudinal studies.

OBJECTIVES: Previous studies have identified several subgroups (ie, latent trajectories) with distinct disease progression among people with dementia. However, the methods and results were not always consistent. This study aims to perform a coordinated analysis of latent trajectories of cognitive and functional progression in dementia across two datasets. METHODS: Included and analyzed using the same statistical approach were 1628 participants with dementia from the US National Alzheimer's Coordinating Center (NACC) and 331 participants with dementia from the Dutch Clinical Course of Cognition and Comorbidity study (4C-Study). Trajectories of cognition and instrumental activities of daily living (IADL) were modeled jointly in a parallel-process growth mixture model. RESULTS: Cognition and IADL tended to decline in unison across the two samples. Slow decline in both domains was observed in 26% of the US sample and 74% of the Dutch sample. Rapid decline in cognition and IADL was observed in 7% of the US sample and 26% of the Dutch sample. The majority (67%) of the US sample showed moderate cognitive decline and rapid IADL decline. CONCLUSIONS: Trajectories of slow and rapid dementia progression were identified in both samples. Despite using the same statistical methods, the number of latent trajectories was not replicated and the relative class sizes differed considerably across datasets. These results call for careful consideration when comparing progression estimates in the literature. In addition, the observed discrepancy between cognitive and functional decline stresses the need to monitor dementia progression across multiple domains.

Predicting Cognitive and Functional Trajectories in People With Late-Onset Dementia: 2 Population-Based Studies.

OBJECTIVES: Previous studies have shown large heterogeneity in the progression of dementia, both within and between patients. This heterogeneity offers an opportunity to limit the global and individual burden of dementia through the identification of factors associated with slow disease progression in dementia. We explored the heterogeneity in dementia progression to detect disease, patient, and social context factors related to slow progression. DESIGN: Two longitudinal population-based cohort studies with follow-up across 12 years. SETTING AND PARTICIPANTS: 512 people with incident dementia from Stockholm (Sweden) contributed to the Kungsholmen Project and the Swedish National Study of Aging and Care in Kungsholmen. METHODS: We measured cognition using the Mini-Mental State Examination and daily functioning using the Katz Activities of Daily Living Scale. Latent classes of trajectories were identified using a bivariate growth mixture model. We then used bias-corrected logistic regression to identify predictors of slower progression. RESULTS: Two distinct groups of progression were identified; 76% (n = 394) of the people with dementia exhibited relatively slow progression on both cognition and daily functioning, whereas 24% (n = 118) demonstrated more rapid worsening on both outcomes. Predictors of slower disease progression were Alzheimer's disease (AD) dementia type [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.15-3.71], lower age (OR 0.88, 95% CI 0.83-0.94), fewer comorbidities (OR 0.77, 95% CI 0.66-0.90), and a stronger social network (OR 1.72, 95% CI 1.01-2.93). CONCLUSIONS/IMPLICATIONS: Lower age, AD dementia type, fewer comorbidities, and a good social network appear to be associated with slow cognitive and functional decline. These factors may help to improve the counseling of patients and caregivers and to optimize the planning of care in dementia.

Evaluation of a Computer-Based HIV Education Program for Adults Living with HIV.

This study evaluated a computer-delivered HIV and antiretroviral treatment education program in adults (N = 102) living with detectable HIV viral loads (> 200 copies/mL). The self-paced program provided immediate feedback for responses and financial incentives for responding correctly. The program was divided into three courses and a test of content from all three courses was delivered before and after participants completed each course. Test scores on the content delivered in Courses 1, 2 and 3 improved only after participants completed training on the relevant course. Initial test scores were positively correlated with health literacy and academic achievement; were negatively correlated with viral load; and were lowest for participants living in poverty. Education, academic achievement, and health literacy were related to how much participants learned following each course. Computer-based education is a convenient, effective approach to promoting an understanding of HIV and its treatment.

The effects of extended-release injectable naltrexone and incentives for opiate abstinence in heroin-dependent adults in a model therapeutic workplace: A randomized trial.

AIM: To determine whether extended-release injectable naltrexone (XR-NTX), incentives for opiate abstinence, and their combination reduce opiate use compared to a usual care control and whether the combination reduces opiate use compared to either treatment alone. DESIGN: Randomized 2 × 2 single-site controlled trial conducted from November 2012 through May 2016. After a detoxification and oral naltrexone induction, participants were assigned to a Usual Care, Abstinence Incentives, XR-NTX, or XR-NTX plus Abstinence Incentives group for a six-month intervention period. SETTING: A model therapeutic workplace where participants could work on automated computer programs that targeted job-skills training for 4 h every weekday for 24 weeks and earn about $10 per hour. PARTICIPANTS: 84 heroin-dependent adults who were unemployed and medically approved for naltrexone. Most participants were male (71.4%), African American (80.1%), and cocaine dependent (71.4%). MEASUREMENTS: The primary outcome measure was the percentage of urine samples negative for opiates that were collected at once weekly assessments (24 per participant) that were not part of the intervention and for which participants were paid $10 for completing. INTERVENTION: Participants who attended the workplace provided thrice-weekly urine samples. Abstinence Incentives participants had to provide opiate-free urine samples to maintain maximum pay. XR-NTX participants received one injection every 4 weeks and were required to take injections in order to work and to maintain maximum pay. Usual Care participants were not offered XR-NTX and opiate urinalysis results did not affect pay. FINDINGS: A large percentage (65 of 149; 43.6%) of individuals failed the induction protocol required for randomization and to be eligible to receive XR-NTX. When missing urine samples were considered positive, there was no significant interaction between XR-NTX and Abstinence Incentives. XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (81.3%, SD 39.0%) than XR-NTX participants (64.5%, SD 47.9%; aOR 10.4, 95% CI 1.3-85.5; P = .030). When urine samples were not replaced, there was a significant interaction between XR-NTX and Abstinence Incentives (aOR 77.0, 95% CI 1.3-4432;P = 0.036); XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (99.6%, SD 0.1%) than XR-NTX participants (85.0%, SD 35.7%; aOR 147.6, 95% CI 6.3-3472; P = 0.002), Abstinence Incentives participants (91.9%, SD 27.3%; aOR 121.7, 95% CI 4.8-3067; P =0.004), and Usual Care participants (78.7%, SD 41.0%; aOR 233.4, 95% CI 9.4-5814; P <.001). No other group differences were significant. CONCLUSION: XR-NTX plus incentives for opiate abstinence increased opiate abstinence, but XR-NTX alone did not. XR-NTX can promote opiate abstinence when it is combined with incentives for opiate abstinence in a model therapeutic workplace.

Neurometabolites and associations with cognitive deficits in mild cognitive impairment: a magnetic resonance spectroscopy study at 7 Tesla.

The levels of several brain metabolites were investigated in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) in 13 healthy controls (HC) and 13 patients with mild cognitive impairment (MCI) using single-voxel magnetic resonance spectroscopy at 7T. Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr). The effect of diagnosis on metabolite levels, and relationships between metabolite levels and memory and executive function, correcting for age, were investigated. MCI patients showed significantly decreased GABA/tCr (ACC, PCC), Glu/tCr (PCC), and NAA/tCr (PCC), and significantly increased mI/tCr (ACC). In the combined group, worse episodic verbal memory performance was correlated with lower Glu/tCr (PCC), lower NAA/tCr (PCC), and higher mI/tCr (ACC, PCC). Worse verbal fluency performance was correlated with lower GSH/tCr (PCC). In summary, MCI is associated with decreased GABA and Glu, most consistently in the PCC. Further studies in larger patient samples should be undertaken to determine the utility of 7T magnetic resonance spectroscopy in detecting MCI-related neurochemical changes.

Working Memory Training for Adolescents With Cannabis Use Disorders: A Randomized Controlled Trial.

Adolescent cannabis use is associated with working memory impairment. The present randomized controlled trial assigned adolescents ages 14 to 21 enrolled in cannabis use treatment to receive either working memory training (experimental group) or a control training (control group) as an adjunctive treatment. Cognitive function, drug use, and other outcomes were assessed before and after training. We observed few differences in cognitive, functional, or self-reported drug use outcomes as a function of training group, although tetrahydrocannabinol (THC) urinalysis results favored the experimental group. These findings are similar to previous studies in substance users, which have shown limited transfer effects for working memory training.

Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

BACKGROUND: Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. OBJECTIVE: To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. METHODS: 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. RESULTS: DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. CONCLUSION: DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.

MIND at Home-Streamlined: Study protocol for a randomized trial of home-based care coordination for persons with dementia and their caregivers.

BACKGROUND: Dementia is associated with high health care costs, premature long-term care (LTC) placement, medical complications, reduced quality of life, and caregiver burden. Most health care providers and systems are not yet organized or equipped to provide comprehensive long-term care management for dementia, although a range of effective symptoms and supportive care approaches exist. The Maximizing Independence at Home-Streamlined (MIND-S) is a promising model of home-based dementia care coordination designed to efficiently improve person-centered outcomes, while reducing care costs. This report describes the rationale and design of an NIA-funded randomized controlled trial to test the impact of MIND-S on time to LTC placement, person with dementia outcomes (unmet needs, behavior, quality of life), family caregiver outcomes (unmet needs, burden), and cost offset at 18 (primary end point) and 24 months, compared to an augmented usual care group. METHODS: This is a 24-month, parallel group, randomized trial evaluating MIND-S in a cohort of 304 community-living persons with dementia and their family caregivers in Maryland. MIND-S dyads receive 18 months of care coordination by an interdisciplinary team comprised of trained non-clinical community workers (e.g. Memory Care Coordinators), a registered nurse, and a geriatric psychiatrist. Intervention components include in-home dementia-related needs assessments; individualized care planning; implementation of standardized evidence-based care strategy protocols; and ongoing monitoring and reassessment. Outcomes are assessed by blinded evaluators at baseline, 4.5, 9, 13.5, 18, and 24 months. DISCUSSION: Trial results will provide rigorous data to inform innovations in effective system-level approaches to dementia care.