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Background: Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking., Objectives: Quantify measures of disease progression for use in clinical trials of patients with JOHD., Methods: Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids-JOHD study. The comparator group consisted of children and young adults who were at-risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non-expanded range (gene non-expanded [GNE])., Results: Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was -3.99% compared to -0.06% in the GNE (mean difference [MD], -3.93%; 95% confidence intervals [CI], [-4.98 to -2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of -0.21 point in the GNE (MD, 7.5; 95% CI, [5.71-9.28], FDR < 0·0001)., Conclusions: These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

Objective: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD., Method: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD., Results: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression., Conclusion: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults, and is primarily characterized by muscle weakness and myotonia, yet some of the most disabling symptoms of the disease are cognitive and behavioral. Here we evaluated several of these non-motor symptoms from a cross-sectional time-point in one of the largest longitudinal studies to date, including full-scale intelligence quotient, depression, anxiety, apathy, sleep, and cerebral white matter fractional anisotropy in a group of 39 adult-onset myotonic dystrophy type 1 participants (27 female) compared to 79 unaffected control participants (46 female). We show that intelligence quotient was significantly associated with depression ( P < 0.0001) and anxiety ( P = 0.018), but not apathy ( P < 0.058) or hypersomnolence ( P = 0.266) in the DM1 group. When controlling for intelligence quotient, cerebral white matter fractional anisotropy was significantly associated with apathy ( P = 0.042) and hypersomnolence ( P = 0.034), but not depression ( P = 0.679) or anxiety ( P = 0.731) in the myotonic dystrophy type 1 group. Finally, we found that disease duration was significantly associated with apathy ( P < 0.0001), hypersomnolence ( P < 0.001), IQ ( P = 0.038), and cerebral white matter fractional anisotropy ( P < 0.001), but not depression ( P = 0.271) or anxiety ( P = 0.508). Our results support the hypothesis that cognitive deficits, hypersomnolence, and apathy, are due to the underlying neuropathology of myotonic dystrophy type 1, as measured by cerebral white matter fractional anisotropy and disease duration. Whereas elevated symptoms of depression and anxiety in myotonic dystrophy type 1 are secondary to the physical symptoms and the emotional stress of coping with a chronic and debilitating disease. Results from this work contribute to a better understanding of disease neuropathology and represent important therapeutic targets for clinical trials., Competing Interests: Within the last three years DM has been a scientific consultant and/or received an honoraria/stock options from AMO Pharma, Charles River, Vertex Pharmaceuticals, Triplet Therapeutics, LoQus23 and Small Molecule RNA. DM also had/has research contracts with AMO Pharma and Vertex Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miller, Kruger, Moser, Gutmann, van der Plas, Koscik, Cumming, Monckton and Nopoulos.)

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack years, and postbronchodilator FEV 1 /FVC. We also examined the association between CCA stiffness and cognitive performance among each group separately. Individuals with overlap syndrome ( n = 12) had greater CCA β-stiffness index ( P = 0.015) and lower executive function-processing speed ( P = 0.019) than individuals with COPD alone ( n = 47), OSA alone ( n = 9), and former smoker controls ( n = 21), differences that remained significant after adjusting for age, BMI, sex, pack years, and FEV 1 /FVC. Higher CCA β-stiffness index was associated with lower executive function-processing speed in individuals with overlap syndrome ( r = -0.58, P = 0.047). These data suggest that CCA stiffness is greater and cognitive performance is lower among individuals with overlap syndrome compared with individuals with COPD or OSA alone and that CCA stiffening may be an underlying mechanism contributing to the lower cognitive performance observed in patients with overlap syndrome. NEW & NOTEWORTHY Previous studies have demonstrated greater carotid artery stiffness and lower cognitive function among individuals with COPD alone and OSA alone. However, the present study is the first to demonstrate that individuals that have both COPD and OSA (i.e., overlap syndrome) have greater carotid artery stiffness and lower executive function-processing speed than individuals with either disorder alone. Furthermore, among individuals with overlap syndrome greater carotid artery stiffness is associated with lower executive function-processing speed.

Studies have shown relationships between white matter abnormalities and cognitive dysfunction in myotonic dystrophy type 1 (DM1), but comprehensive analysis of potential structure-function relationships are lacking. Fifty adult-onset DM1 individuals (33 female) and 68 unaffected adults (45 female) completed the Wechsler Adult Intelligence Scale-IV (WAIS-IV) to determine the levels and patterns of intellectual functioning. Neuroimages were acquired with a 3T scanner and were processed with BrainsTools. Regional brain volumes (regions of interest, ROIs) were adjusted for inter-scanner variation and intracranial volume. Linear regression models were conducted to assess if group by ROI interaction terms significantly predicted WAIS-IV composite scores. Models were adjusted for age and sex. The DM1 group had lower Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores than the unaffected group (PRI t (113)  = -3.28, p = 0.0014; WMI t (114)  = -3.49, p = 0.0007; PSI t (114)  = -2.98, p = 0.0035). The group by hippocampus interaction term was significant for both PRI and PSI (PRI (t (111)  = -2.82, p = 0.0057; PSI (t (112)  = -2.87, p = 0.0049)). There was an inverse association between hippocampal volume and both PRI and PSI in the DM1 group (the higher the volume, the lower the intelligence quotient scores), but no such association was observed in the unaffected group. Enlarged hippocampal volume may underlie some aspects of cognitive dysfunction in adult-onset DM1, suggesting that increased volume of the hippocampus may be pathological., (© 2020 Wiley Periodicals, Inc.)

Objective: Myotonic dystrophy is a multisystem disorder caused by a trinucleotide repeat expansion on the myotonic dystrophy protein kinase ( DMPK ) gene. To determine whether wildtype DMPK expression patterns vary as a function of age, we analyzed DMPK expression in the brain from 99 donors ranging from 5 postconceptional weeks to 80 years old., Methods: We used the BrainSpan messenger RNA sequencing and the Yale Microarray data sets, which included brain tissue samples from 42 and 57 donors, respectively. Collectively, donors ranged in age from 5 postconceptional weeks to 80 years old. DMPK expression was normalized for each donor across regions available in both data sets. Restricted cubic spline linear regression models were used to analyze the effects of log-transformed age and sex on normalized DMPK expression data., Results: Age was a statistically significant predictor of normalized DMPK expression pattern in the human brain in the BrainSpan ( p < 0.005) and Yale data sets ( p < 0.005). Sex was not a significant predictor. Across both data sets, normalized wildtype DMPK expression steadily increases during fetal development, peaks around birth, and then declines to reach a nadir around age 10., Conclusions: Peak expression of DMPK coincides with a time of dynamic brain development. Abnormal brain DMPK expression due to myotonic dystrophy may have implications for early brain development., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: The pathological cascades associated with the development of Alzheimer's disease (AD) have a common element: acidosis. T 1 rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T 1 rho imaging and AD-associated pathologies as determined by available diagnostic imaging techniques., Methods: Twenty-seven participants (men, N=13, women, N=14; ages 55-90) across the cognitive spectrum (healthy control subjects [HCs] with normal cognition, N=17; participants with mild cognitive impairment [MCI], N=7; participants with mild AD, N=3) underwent neuropsychological testing, MRI (T 1 -weighted and T 1 rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([ 11 C]Pittsburg compound B for amyloid burden [N=26] and [ 18 F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T 1 rho values and neuropsychological, demographic, and imaging measures were explored., Results: Global mean and median T 1 rho were positively associated with age. After controlling for age, higher global T 1 rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T 1 rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions., Conclusions: Higher T 1 rho values were associated with greater cognitive impairment and pathological burden. T 1 rho, a biomarker that varies according to a feature common to each cascade rather than one that is unique to a particular pathology, has the potential to serve as a metric of neuropathology, theoretically providing a measure for assessing pathological status and for monitoring the neurodegeneration trajectory.

Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery β-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (β=-0.49, SE=0.14; P =0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. β-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.

Background: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention., Methods: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable., Results: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model., Conclusion: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.

Central artery aging, including elevated aortic stiffness, central blood pressure (BP), and pulse pressure (PP), is a novel risk factor for the development of age-associated cognitive dysfunction. Individuals with higher educational attainment may develop greater brain pathology prior to the onset of cognitive decline. However, whether education moderates relations between central artery aging and cognitive performance is unknown. We hypothesized that years of formal education would moderate the relation between central artery aging and cognitive performance in middle-aged/older (MA/O) adults (n = 113, age 67.3 ± 0.7 years). Significant interactions between education*central systolic BP (β = .21, p = .02) and education*central PP (β = .22, p = .01) demonstrated weaker associations between central BP and PP with processing speed performance in those with higher education. Similarly, education moderated the relation between aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) and executive function performance (β = .21, p = .02). To test if the relation between central arterial aging and cognitive performance was captured by a predetermined education threshold, MA/O adults were secondarily categorized as ≤high school (HS) (i.e., ≤12 years, n = 36) or >HS (≥13 years, n = 77). Higher central systolic BP was associated with slower processing speed (≤HS: r = -.59, p < .001 vs. >HS: r = -.25, p = .03) and weaker executive function (r = -.39, p = .03 vs. r = -.32, p = .006). Higher cfPWV was selectively correlated with weaker executive function performance (r = -.39, p = .03) in ≤HS only and this association significantly differed between education groups. Educational attainment appears to moderate the adverse effects of central artery aging on cognitive performance among MA/O adults., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Objective: Electroconvulsive therapy (ECT) is associated with positive outcomes for treatment-resistant mood disorders in the short term. However, there is limited research on long-term cognitive or psychological changes beyond 1 year after -ECT. This study evaluated long-term outcomes in cognitive functioning, psychiatric symptoms, and quality of life for individuals who had undergone ECT., Methods: Eligible participants (N = 294) who completed a brief pre-ECT neuropsychological assessment within the last 14 years were recruited for a follow-up evaluation; a limited sample agreed to follow-up testing (n = 34). At follow-up, participants were administered cognitive measures (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS], Wide Range Achievement Test-4 Word Reading, Trail Making Test, Wechsler Adult Intelligence Scale-Fourth Edition Letter Number Sequence and Digit Span, and Controlled Oral Word Association Test), along with emotional functioning measures (Beck Depression Inventory-Second Edition [BDI-II] and Beck Anxiety Inventory) and the World Health Organization Quality of Life-BREF quality of life measure. Follow-up-testing occurred on average (SD) 6.01 (3.5) years after last ECT treatment., Results: At follow-up, a paired t test showed a large and robust reduction in mean BDI-II score. Scores in cognitive domains remained largely unchanged. A trend was observed for a mean reduction in RBANS visual spatial scores. Lower BDI-II scores were significantly associated with higher RBANS scores and improved quality of life., Conclusions: For some ECT patients, memory, cognitive functioning, and decreases in depressive symptoms can remain intact and stable even several years after ECT. However, the selective sampling at follow-up makes these results difficult to generalize to all post-ECT patients. Future research should examine what variables may predict stable cognitive functioning and a decline in psychiatric symptoms after ECT.

Background and Purpose: To explore the potential for simplified measures of [ 11 C]PIB uptake to serve as a surrogate for cerebral blood flow (CBF) measures, thereby, providing both pathological and functional information in the same scan., Methods: Participants (N = 24, 16 M, 8 F, 57-87 years) underwent quantitative [ 15 O]water imaging and dynamic [ 11 C]PIB imaging. Time-activity curves were created for each participant's regional [ 11 C]PIB data scaled in standardized uptake values (SUVs). The frame in which maximal uptake occurred was defined for each subject (ie, "peak"). The concentration (SUV) for each region at the individual's peak, during the 3.5-4 minute time interval and for the initial 6 minute sum, was determined. R1 (ie, relative delivery using cerebellum as reference tissue) from the simplified reference tissue model 2 was determined for each region. PIB SUVs were compared to the absolute CBF global and regional values (in mL/minute/100 mL) and the R1 values were compared to the cerebellar-normalized rCBF., Results: Significant linear relationships were found for all SUV measures with measures of absolute global and regional CBF that were comparable to the relationship between normalized CBF and R1. The individual SUV peak exhibited the strongest relationship both regionally and globally. All individuals and all regions had highly significant regression slopes. Age, gender, or amyloid burden did not influence the relationship., Conclusion: Early PIB uptake has the potential to effectively serve as a surrogate for global and regional CBF measures. The simple and readily obtainable individual's SUV peak value was the strongest predictor regionally and globally of CBF., (© 2018 by the American Society of Neuroimaging.)

Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [ 15 O]water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P <0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P <0.001) but did not differ between older women and men ( P =0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve ( r =-0.68; P =0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF ( r =0.13; P =0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve ( r =-0.37; P =0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans., (© 2018 American Heart Association, Inc.)

Objective: To determine whether tetrabenazine (TBZ) use is associated with an increased incidence of depression and/or suicidal ideation., Methods: In this retrospective cross-sectional study of the Enroll-HD database, we used multiple logistic regression analyses to determine whether TBZ use is associated with an increased incidence of depression and/or suicidal ideation. For both dependent variables (depression and suicidality), separate analyses were conducted on (1) all participants, (2) only participants with a history of depression, and (3) only participants with no history of depression. Adjustments were made for CAG repeat length, total motor score, total functional capacity, Symbol Digit Modalities Test score, sex, disease duration, history of depression (when applicable), antipsychotic use, and antidepressant use., Results: Compared to participants who were not using TBZ (n = 3,548), TBZ users (n = 543) did not have an increased risk of depression (odds ratio [OR] = 0.78, p = 0.064). Participants taking TBZ actually had a relatively lower risk of suicidality (OR = 0.61, p = 0.043). Among only participants with a history of depression, those using TBZ had a lower incidence of depression (OR = 0.71, p = 0.016) and suicidal ideation (OR = 0.57, p = 0.028) compared to those not using TBZ. Finally, among only participants with no history of depression, TBZ use was not associated with a higher incidence of depression (OR = 1.59, p = 0.18) or suicidality (OR = 1.43, p = 0.66) compared to those who were not using TBZ., Conclusions: TBZ use was not associated with an increased incidence of depression or suicidality. These findings suggest that TBZ may be safe to use in patients with Huntington disease who have a history of depression., (© 2018 American Academy of Neurology.)

Objective: This study examined the association of perceived cognitive difficulties with objective cognitive performance in former smokers. We hypothesized that greater perceived cognitive difficulties would be associated with poorer performance on objective executive and memory tasks., Method: Participants were 95 former smokers recruited from the COPDGene study. They completed questionnaires (including the Cognitive Difficulties Scale [CDS] and the Hospital Anxiety and Depression Scale [HADS]), neuropsychological assessment, and pulmonary function testing. Pearson correlations and t-tests were conducted to examine the bivariate association of the CDS (total score and subscales for attention/concentration, praxis, delayed recall, orientation for persons, temporal orientation, and prospective memory) with each domain of objective cognitive functioning (memory recall, executive functioning/processing speed, visuospatial processing, and language). Simultaneous multiple linear regression was used to further examine all statistically significant bivariate associations. The following covariates were included in all regression models: age, sex, pack-years, premorbid functioning (WRAT-IV Reading), HADS total score, and chronic obstructive pulmonary disease (COPD) status (yes/no based on GOLD criteria)., Results: In regression models, greater perceived cognitive difficulties overall (using CDS total score) were associated with poorer performance on executive functioning/processing speed tasks (b = -0.07, SE = 0.03, p = .037). Greater perceived cognitive difficulties on the CDS praxis subscale were associated with poorer performance on executive functioning/processing speed tasks (b = -3.65, SE = 1.25, p = .005), memory recall tasks (b = -4.60, SE = 1.75, p = .010), and language tasks (b = -3.89, SE = 1.39, p = .006)., Conclusions: Clinicians should be aware that cognitive complaints may be indicative of problems with the executive functioning/processing speed and memory of former smokers with and without COPD.

Objective: To investigate the relationship between substances of abuse and age at motor onset (AMO) in patients with Huntington disease (HD) in a large and diverse patient population., Methods: This was a retrospective, observational study of the Enroll-HD database. Participants were determined to belong to 1 of 3 substance abuse groups: (1) tobacco abusers, (2) alcohol abusers, and (3) drug abusers. A group of participants who had never abused substances served as a control group. The average AMO of patients in the substance abuse groups was compared to the control group. The number of CAG repeats was used as a covariate in all analyses., Results: The average difference in AMOs of participants in the tobacco (n = 566), alcohol (n = 374), and drug abuse groups (n = 217) compared to the control group (n = 692) were 2.3 ( F 1, 1,258 = 33.8, p < 0.0001), 1.0 ( F 1, 1,066 = 4.2, p = 0.04), and 3.3 ( F 1, 909 = 29.7, p < 0.0001) years earlier, respectively. In all substance abuse groups, the AMO was lowered to a greater degree in female participants than it was in male participants., Conclusions: Substances of abuse have a strong effect on the AMO in patients with HD. These effects seem to be amplified in women with HD compared to men. These results may provide a safe intervention capable of adding disease-free years to patients with HD., (© 2017 American Academy of Neurology.)

Objective: Anxious and depressive states are associated with increased cardiovascular disease (CVD) risk and a proinflammatory phenotype, although the latter appears to be at least partially explained by adiposity. It was hypothesized that depression and anxiety would be associated with elevated inflammation independent of adiposity in persons with obesity at high risk of CVD., Methods: This study explored the relation between baseline anxiety as measured by the Beck Anxiety Inventory and depression as measured by the Beck Depression Inventory-II and baseline serum c-reactive protein (CRP) in a cross-sectional sample of 100 participants [mean (SD) age 57.8 (7.7) years; 64% female] with obesity [mean (SD) body mass index, BMI 37.3 (5.5) kg/m 2 ] enrolled in a clinical trial for pharmacological weight loss., Results: Beck Anxiety Inventory, but not Beck Depression Inventory-II, scores were significantly correlated with CRP (ρ = 0.28, P = 0.005). BMI was also highly correlated with CRP (ρ = 0.42, P < 0.0001). In multivariate models, the relation between anxiety and CRP remained significant (P = 0.038), independent of BMI, age, and sex., Conclusions: Anxiety, but not depression, was associated with elevated inflammation in persons with obesity beyond that attributable to higher BMI. Further study is warranted to assess whether anxiety represents a potential therapeutic target to mitigate corresponding CVD risk associated with elevated inflammation in persons with obesity., (© 2016 The Obesity Society.)

We sought to characterize the relationship between integrity of the white matter underlying the ventral anterior cingulate (vAC) and depressive symptoms in older adults with atherosclerotic vascular disease (AVD), a condition associated with preferential degeneration of the white matter. The vAC was defined as including white matter underlying ventral Brodmann Area 24 and Brodmann Area 25, corresponding with the "subcallosal" and "subgenual" cingulate respectively. This region of interest was chosen based on the preponderance of evidence that the white matter in the region plays a critical role in the manifestation of depressive symptoms. Participants had current unequivocal diagnoses of AVD and were between 55 and 90 years-old. Fractional anisotropy (FA) was used as an index of white matter integrity and organization. Whole-brain mean diffusivity (MD) was used as an index of global white matter lesion burden. Depressive symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R) Depression Scale. Depressive symptoms were significantly related to low FA in the right vAC (r = -0.356, df = 30, p = 0.045) but not the left vAC (r = 0.024, df = 30, p = 0.896) after controlling for total brain MD (a statistical control for global white matter lesion burden). Further, depressive symptoms were significantly related to low FA in the right vAC (r = -0.361, df = 31, p = 0.039), but not the left vAC (r = 0.259, df = 31, p = 0.145) when controlled for the contralateral vAC FA. The correlation coefficients for this follow-up analysis were found to be significantly different between left and right vAC (Z = 2.310, p = 0.021). Poor white matter health in the vAC may be a biological mechanism for depressive symptoms in older adults with vascular disease. Further studies may corroborate that the right vAC plays a unique role in depressive symptom manifestation in cases where the white matter is preferentially affected, as is the case in AVD. This could lead to future targeting of the region for somatic antidepressant treatment, as well as the development of a precise approach for patients with white matter damage, which could produce significant improvement in quality of life, medical morbidity, and mortality.

This study examined the efficacy of antidepressant treatment for preventing the onset of generalized anxiety disorder (GAD) among patients with recent stroke. Of 799 patients assessed, 176 were randomized, and 149 patients without evidence of GAD at the initial visit were included in this double-blind treatment with escitalopram (N=47) or placebo (N=49) or non-blinded problem-solving therapy (PST; 12 total sessions; N=53). Participants given placebo over 12 months were 4.95 times more likely to develop GAD than patients given escitalopram and 4.00 times more likely to develop GAD than patients given PST. Although these results should be considered preliminary, the authors found that both escitalopram and PST were effective in preventing new onset of post-stroke GAD.

Background: The Mark 3 (M3) water power pump is an integral piece of wildfire fighting equipment. However, it is provided to fire stations without a carrying harness. The currently-used carrying harness is very uncomfortable, especially when carrying the pumps considerable distance in a forest to reach a water source., Objective: The purpose of this study was to advise the Ontario Ministry of Natural Resources on the selection of a new M3 load carriage system., Participants: Twenty Fire Rangers wore the three systems (Original, Prototype, and Modified) through a circuit of tasks representative of their working environment., Methods: Subjective and objective approaches were combined to assess and rank the M3 carriage systems. Subjective visual analogue scale ratings were obtained for ease of loading/unloading, comfort, system stability, and overall performance. Tri-axial accelerometers were mounted on each pump and at the sternum of each participant to determine relative pump-carrier accelerations., Results: Overall, the Prototype was ranked as the best system; it resulted in the lowest relative pump-carrier accelerations on 10 out of 15 objective measures, and also received a first place ranking on all subjective measures., Conclusion: It was recommended that the Prototype be implemented as the M3 carriage system for fire suppression teams.

Atherosclerotic vascular disease (AVD) is endemic to the developed world, with known negative outcomes for cognition and brain health. The effects of AVD on the white matter fibers of the brain have not yet been studied using diffusion tensor imaging (DTI). This study examined differences in fractional anisotropy (FA) between AVD and healthy comparison (HC) participants, and described the regional patterns of FA in each group. AVD participants were hypothesized to have lower FA than HC participants, indicating abnormalities in white matter health or organization. 1.5 T diffusion tensor imaging was performed in 35 AVD and 22 HC participants. Mean FA measures were calculated for the white matter of the whole brain, as well for individual lobes. Globally and in every brain region measured except the temporal lobes, there were significant effects of group where AVD participants had lower FA values than their HC counterparts. Group differences in FA remained significant when controlled for white matter hyperintensity (WMH) volume, suggesting that FA detects white matter abnormality above and beyond what is measurable using the older WMH technique. These findings suggest a likely neural substrate underlying the changes in cognition and mood reported in atherosclerotic vascular disease patients., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Clinical anxiety disorders are associated with white matter hyperintensities and diffusion abnormalities measured using diffusion tensor imaging. However, it is not known if this association extends into individuals with mild anxious symptoms without formal diagnosis, in those who are older, or in those who have atherosclerosis. The current study explores whether white matter integrity and/or organization significantly associates with anxious symptoms in older adults with and without atherosclerosis., Methods: We recruited older adults (ages 55-90 years); 35 with clinically diagnosed atherosclerotic vascular disease (AVD) and 22 without AVD. Anxious symptoms were measured using the validated Symptom Checklist-90-Revised. Fractional anisotropy (FA), a proxy for white matter organization and health, was measured in the white matter globally, by lobe, and in several smaller regions of interest suggested by the literature. Partial correlations between anxious symptoms and FA were calculated, controlling for significant covariates., Results: Participants with and without AVD did not differ in severity of anxious symptom endorsement. There was a unique inverse relationship between white matter health and anxious symptoms in the AVD participants, but not in healthy comparisons. Significant relationships were observed in the superior longitudinal fasciculus (r = -0.476, df = 32, p = 0.004), as well as the cingulum bundle, the frontal lobes, and the parietal lobes., Conclusions: Anxiety symptoms uniquely correlated with low FA in older adults with atherosclerosis. These findings may have implications for future research on the topic of anxiety in aging and vascular disease and warrant replication., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: Apathy occurs frequently following stroke and prior studies have demonstrated the negative effect of apathy on recovery from stroke. This study was a secondary analysis examining the efficacy of escitalopram, problem-solving therapy (PST), or placebo administered for 1 year to prevent the onset of apathy among patients with recent stroke., Methods: Patients within 3 months of an index stroke who did not meet DSM-IV diagnostic criteria for major or minor depression and who did not have a serious comorbid physical illness were enrolled. Patients were recruited from three sites: University of Iowa, University of Chicago, and Burke Rehabilitation Hospital. One hundred fifty-four patients without evidence of apathy at initial evaluation were included in the randomized controlled trial using escitalopram (10 mg patients ≤65 years; 5 mg patients >65 years) (N = 51) or placebo (N = 47) or non-blinded PST (12 total sessions) (N = 56) over 1 year. At 3, 6, 9, and 12 months, patients were assessed for diagnosis and severity of apathy using the Apathy Scale., Results: Using a Cox proportional hazards model of time to onset of apathy, participants given placebo were 3.47 times more likely to develop apathy than patients given escitalopram and 1.84 times more likely to develop apathy than patients given PST after controlling for age, sex, cognitive impairment, and diabetes mellitus status (adjusted hazard ratio: 3.47, 95% CI: 1.79-6.73 [escitalopram group]; adjusted hazard ratio: 1.84, 95% CI: 1.21-2.80 [PST group])., Conclusion: Escitalopram or PST was significantly more effective in preventing new onset of apathy following stroke compared with placebo., (Copyright © 2013. Published by Elsevier Inc.)

Objective: This prospective study examined the course of cognitive, physical, and social impairment among patients who developed apathy during the first year after stroke., Methods: Patients diagnosed with apathy (N = 23) were compared with patients who had no apathy (N = 33) at initial, 3, 6, 9, and 12 months after stroke for severity of global cognitive impairment as measured by Mini-Mental State Examination, severity of impairment in activities of daily living (ADLs) as measured by Functional Independence Measure, and severity of impairment in social functioning as measured by Social Functioning Exam., Results: A total of 41.1% of patients met diagnostic criteria for apathy during the first year after stroke. The mean time from stroke to onset of apathy was 3.8 (3.3 SD) months and the mean duration was 5.6 (2.3 SD) months. Using a linear mixed model, after controlling for age, initial severity of impairment, and major depression, patients in the apathy group had significantly less recovery in cognition (t(149) = -2.06; p = 0.0411) and ADLs (t(104) = -3.37; p = 0.0011) during the first year after stroke compared with nonapathic patients., Conclusion: Apathy is common after stroke and leads to less recovery in cognition and ADLs over the first year after stroke compared with similar nonapathic patients., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Anxiety predicts cardiovascular events, although the mechanism remains unclear. We hypothesized that anxiety symptoms will correlate with impaired resistance and conduit vessel function in participants aged 55 to 90 years., Methods: Anxiety symptoms were measured with the Symptom Checklist-90--Revised in 89 participants with clinically diagnosed atherosclerotic cardiovascular disease and 54 healthy control participants. Vascular function in conduit arteries was measured using flow-mediated dilatation, and vascular function in forearm resistance vessels (FRVs) was measured using intra-arterial drug administration and plethysmography., Results: Anxiety symptoms were not associated with flow-mediated dilatation in either group. Participants with atherosclerosis exhibited significant inverse associations of anxiety symptoms with FRV dilatation (acetylcholine: β = -.302, p = .004). Adjustment for medication, risk factors, and depression symptoms did not alter the association between anxiety and FRV dysfunction, except for body mass index (BMI; anxiety: β = -.175, p = .060; BMI: β = -.494, p < .001). Although BMI was more strongly associated with FRV function than anxiety, combined BMI and anxiety accounted for greater variance in FRV function than either separately. Control participants showed no association of anxiety with FRV function., Conclusions: Anxiety is uniquely and substantially related to poorer resistance vessel function (both endothelial and vascular smooth muscle functions) in individuals with atherosclerosis. These relationships are independent of medication, depression, and cardiovascular risk factors, with the exception of BMI. These findings support the concept that anxiety potentially increases vascular events through worsening of vascular function in atherosclerotic disease.

Social isolation is common among individuals with isolated cleft lip and palate (ICLP), but the available data on why this may be are mixed. We present a novel theory relating to reduced social motivation in ICLP, called the social abulia hypothesis. Based on this hypothesis, we predicted that reduced social motivation would lead to reduced responsiveness to negative social feedback, in terms of both explicit responses and noncontrolled, psychophysiological responses. Twenty males with ICLP and 20 normal comparison males between 13 and 25 years old participated in the study. Social motivation was examined by measuring participants' response to negative social feedback (social exclusion). Additionally, psychophysiological reactivity to positive and negative social stimuli was measured. In order to rule out other potential contributors to social isolation, we tested basic social perception, emotion recognition, and social anxiety. In line with the social abulia hypothesis, we show that negative social feedback had less of an effect on males with ICLP than on healthy male peers, which was evident in explicit responses and noncontrolled, psychophysiological responses to negative social feedback. Our results could not be attributed to problems in social perception, a lack of understanding facial expressions, or increased social anxiety, as groups did not differ on these constructs. This study suggests that current views on social isolation in ICLP may need to be reconsidered to include the possibility that isolation in this population may be the direct result of reduced social motivation.

Environmental factors may contribute as much as one-third of the variance in Huntington disease (HD) age of onset. Substance abuse is a risk factor for other neurodegenerative disorders; however, whether substance abuse influences HD age of onset is not well established. This study investigated the relationships between alcohol, drug, and tobacco abuse and HD age of onset in 136 participants with symptomatic HD. CAG repeat length was used as a covariate in all analyses, as it represents the most significant determinant of HD age of onset. The relationship between substance abuse, HD age of onset, and sex was also examined, as women may experience greater medical harm from substance abuse. Lifetime alcohol abuse and lifetime drug abuse were associated with earlier age of HD onset; a similar trend was seen for current tobacco abuse. For women, lifetime alcohol abuse was associated with earlier onset of HD, with a similar trend for lifetime drug abuse. However, alcohol, drug, and tobacco abuse were not significantly associated with age of onset in men. Further work is needed to determine whether substance abuse is a causative risk factor for earlier onset of HD, and why the environmental factors associated with age of onset vary by sex.

Background: The goals of this study were to determine the relationship between anxious symptoms and cognitive functioning in a non-demented, community-dwelling older adults sample (n = 48), and to determine the effect of depressive symptoms upon this relationship., Methods: Anxious and depressive symptoms were assessed using the Symptom Checklist 90--Revised. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status., Results: Results indicated that although both cognitive functioning and anxious symptoms were within normal limits in this sample, anxious symptoms showed a significant, inverse relationship with global cognitive function [r(47) = -0.400, p = 0.005]. In addition, specific relationships were noted between severity of anxious symptoms and visuospatial/constructional ability as well as immediate and delayed memory. With regard to the secondary objective, both anxiety and depressive symptoms together accounted for the highest level of variance [R(2)  = 0.175, F(2, 45) = 4.786, p = 0.013] compared with anxiety [R(2) (47) = 0.160, p = 0.005] and depression [R(2) (47) = 0.106, p = 0.024] alone. Nevertheless, neither anxious nor depressive symptoms emerged as a unique correlate with cognitive ability [r(47) = -0.278, p = 0.058; r(48) = -0.136, p = 0.363, respectively]., Conclusion: This study demonstrates that subthreshold anxiety symptoms and cognitive functioning are significantly related even among generally healthy older adults whose cognitive ability and severity of anxious symptoms are within broad normal limits. These findings have implications both for clinical care of older patients, as well as for cognitive research studies utilizing this population., (Copyright © 2011 John Wiley & Sons, Ltd.)

Antidepressant usage in prodromal Huntington Disease (HD) remains uncharacterized, despite its relevance in designing experiments, studying outcomes of HD, and evaluating the efficacy of therapeutic interventions. We searched baseline medication logs of 787 prodromal HD and 215 healthy comparison (HC) participants for antidepressant use. Descriptive and mixed-effects logistic regression modeling characterized usage across participants. At baseline, approximately one in five prodromal HD participants took antidepressants. Of those, the vast majority took serotonergic antidepressants (selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI)). Significantly more prodromal HD participants used serotonergic antidepressants than their HC counterparts. Because of the prevalence of these medications, further analyses focused on this group alone. Mixed-effects logistic regression modeling revealed significant relationships of both closer proximity to diagnosis and female sex with greater likelihood to be prescribed a serotonergic antidepressant. More prodromal HD participants took antidepressants in general and specifically the subclass of serotonergic antidepressants than their at-risk counterparts, particularly when they were closer to predicted time of conversion to manifest HD. These propensities must be considered in studies of prodromal HD participants., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This study was designed to determine the relationships between positron emission tomography (PET)-based quantitative measures of cerebral blood flow and cerebrovascular reserve and neuropsychological functioning in elderly individuals with atherosclerotic vascular disease. It was hypothesized that cerebrovascular function would be significantly associated with neuropsychological functioning. Results showed that both baseline global cerebral blood flow and cerebrovascular reserve were significantly associated with global neuropsychological functioning, when controlling for age and sex. Cerebrovascular reserve was additionally associated with performance on measures of memory and attention. Additional research is needed to determine whether measures of cerebral blood flow can be used to predict cognitive decline.

Background and Purpose: The purpose of this study was to compare escitalopram, problem-solving therapy, and placebo to prevent poststroke depression during 6 months after discontinuation of treatment., Methods: We examined for depression 33 patients assigned to placebo, 34 to escitalopram, and 41 to problem-solving therapy., Results: After controlling for age, gender, prior mood disorder, and severity of stroke, new-onset major depression and Hamilton Depression scores were significantly higher 6 months after escitalopram was discontinued compared with the problem-solving therapy or placebo groups., Conclusions: Discontinuation of escitalopram may increase poststroke depressive symptoms.

Objective: Practice effects on cognitive tests have been shown to further characterize patients with amnestic mild cognitive impairment (aMCI) and may provide predictive information about cognitive change across time. We tested the hypothesis that a loss of practice effects would portend a worse prognosis in aMCI., Design: Longitudinal, observational design following participants across 1 year., Setting: Community-based cohort., Participants: Three groups of older adults: 1) cognitively intact (n = 57), 2) aMCI with large practice effects across 1 week (MCI + PE, n = 25), and 3) aMCI with minimal practice effects across 1 week (MCI - PE, n = 26)., Measurements: Neuropsychological tests., Results: After controlling for age and baseline cognitive differences, the MCI - PE group performed significantly worse than the other groups after 1 year on measures of immediate memory, delayed memory, language, and overall cognition., Conclusions: Although these results need to be replicated in larger samples, the loss of short-term practice effects portends a worse prognosis in patients with aMCI.

We examined the Trail Making Test (TMT) in a sample of 767 participants with prodromal Huntington disease (prodromal HD) and 217 healthy comparisons to determine the contributions of motor, psychiatric, and cognitive changes to TMT scores. Eight traditional and derived TMT scores were also evaluated for their ability to differentiate prodromal participants closer to estimated age of diagnosis from those farther away and prodromal individuals from healthy comparisons. Results indicate that motor signs only mildly affected Part A, and psychiatric symptoms did not affect either part. Tests of perceptual processing, visual scanning, and attention were primarily associated with Part A, and executive functioning (response inhibition, set-shifting), processing speed, and working memory were associated with Part B. Additionally, TMT scores differentiated between healthy comparisons and prodromal HD individuals as far as 9-15 years before estimated diagnosis. In participants manifesting prodromal motor signs and psychiatric symptoms, the TMT primarily measures cognition and is able to discriminate between groups based on health status and estimated time to diagnosis.

Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients.

This study was conducted to assess gender differences in cognition in elderly individuals (N = 88; 38 women, 50 men) with atherosclerotic vascular disease (AVD) and to determine whether these were attributable to differences in vascular health. Assessments included neuropsychological testing and measurement of forearm vascular function using venous occlusion plethysmography. There was a significant female advantage on multiple neuropsychological tests. This gender effect was reduced somewhat but remained significant when controlling for education and vascular function. Our study suggests that gender differences in cognition persist into older age and are not primarily due to gender differences in vascular health.

The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer's disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more severely impaired geriatric patients, over one third had EI scores that fell above suggested cutoff scores (e.g., 37% in nursing home residents, 33% in probable Alzheimer's disease). In the cognitively intact sample, older and less educated patients were more likely to have scores suggestive of poor effort. Education effects were observed in three of the four clinical samples. Overall cognitive functioning was significantly correlated with EI scores, with poorer cognition being associated with greater suspicion of low effort. The current results suggest that age, education, and level of cognitive functioning should be taken into consideration when interpreting EI results and that significant caution is warranted when examining EI scores in elders suspected of having dementia.

Background: Cognitive decline has been reported in Huntington disease (HD), as well as in the period before diagnosis of motor symptoms (i.e., pre-HD). However, the severity, frequency, and characterization of cognitive difficulties have not been well-described. Applying similar cutoffs to those used in mild cognitive impairment (MCI) research, the current study examined the rates of subtle cognitive dysfunction (e.g., dysfunction that does not meet criteria for dementia) in pre-HD., Methods: Using baseline data from 160 non-gene-expanded comparison participants, normative data were established for cognitive tests of episodic memory, processing speed, executive functioning, and visuospatial perception. Cutoff scores at 1.5 standard deviations below the mean of the comparison group were then applied to 575 gene-expanded pre-HD participants from the observational study, PREDICT-HD, who were stratified by motor signs and genetic risk for HD., Results: Nearly 40% of pre-HD individuals met criteria for MCI, and individuals closer to HD diagnosis had higher rates of MCI. Nonamnestic MCI was more common than amnestic MCI. Single-domain MCI was more common than multiple-domain MCI. Within the nonamnestic single-domain subtype, impairments in processing speed were most frequent., Conclusions: Consistent with the Alzheimer disease literature, MCI as a prodromal period is a valid concept in pre-HD, with nearly 40% of individuals showing this level of impairment before diagnosis. Future studies should examine the utility of MCI as a marker of cognitive decline in pre-HD.

Previous research indicates that individuals with Anorexia Nervosa (AN) often experience some degree of neuropsychological dysfunction. Although most aspects of cognition improve with treatment, factors that predict neuropsychological improvement remain elusive. The present study investigated whether cognitive reserve, the estimated level of premorbid cognitive functioning, and AN subtype predicted neuropsychological improvement during inpatient treatment for AN. Neuropsychological functioning was assessed pre- and post-hospitalization in 28 women with AN (18 with restricting type and 10 with binge-eating/purging type), and cognitive reserve was estimated at admission using a word reading test. Level of cognitive reserve and AN subtype were both significant predictors of neuropsychological improvement in this sample. Cognitive reserve was significantly associated with improvements in verbal memory, semantic fluency, basic auditory attention and visuospatial construction. Participants with AN binge-eating/purging type demonstrated significantly greater neuropsychological improvement during treatment than did participants with AN restricting type. Information about cognitive reserve and AN subtype may provide clinicians with valuable prognostic information and help guide treatment.

Objective: This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington's disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC)., Method: Participants (747 pr-HD: 188 NC) listened to tones presented at 550-ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and other demographic factors., Results: Pr-HD participants showed significantly less timing precision than NC. Comparison of pr-HD and NC participants showed a significant performance difference on two task administration conditions (dominant hand: p < .0001; alternating thumbs: p < .0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t = -11.14, df = 920, p < .0001; alternating thumbs: t = -11.32, df = 918, p < .0001). Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and rate of decline increases with estimated proximity to diagnosis in both conditions (dominant hand: t = -2.85, df = 417, p = .0045; alternating thumbs: t = -3.56, df = 445, p = .0004). Effect sizes based on adjusted mean annual change ranged from -0.34 to 0.25 in the longitudinal model., Conclusions: The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically mediated improvement or maintenance of function.

Assessing cognitive change in older adults is a common use of neuropsychological services, and neuropsychologists have utilized several strategies to determine if a change is "real," "reliable," and "meaningful." Although standardized regression-based (SRB) prediction formulas may be useful in determining change, SRBs have not been widely applied to older adults. The current study sought to develop SRB formulas on a group of 127 community-dwelling older adults for several widely used neuropsychological measures. In addition to baseline test scores and demographic information, the current study also examined the role of short-term practice effects in predicting test scores after 1 year. Consistent with prior research on younger adults, baseline test performances were the strongest predictors of future test performances, accounting for 25%-58% of the variance. Short-term practice effects significantly added to the predictability of all nine of the cognitive tests examined (3%-22%). Future studies should continue extending SRB methodology for older adults, and the inclusion of practice effects appears to add to the prediction of future cognition.

Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after 1 year, two sets of SRBs were developed: (1) those predicting performance on the same test, and (2) those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, 1-year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same and different tests, as well as beginning to examine domain-based SRBs.

Memory assessment is an important component of a neuropsychological evaluation, but far fewer visual than verbal memory instruments are available. We examined the preliminary psychometric properties and clinical utility of a novel, motor-free paper and pencil visuospatial memory test, the Indiana faces in places test (IFIPT). The IFIPT and general neuropsychological performance were assessed in 36 adults with amnestic mild cognitive impairment (aMCI) and 113 older adults with no cognitive impairment at baseline, 1 week, and 1 year. The IFIPT is a visual memory test with 10 faces paired with spatial locations (three learning trials and non-cued delayed recall). Results showed that MCI participants scored lower than controls on several variables, most notably total learning (p < .001 at all three time points), delayed recall (baseline p = .03, 1 week p < .001, 1 year p < .001), and false-positive errors (range p = .03 to <0.001). The IFIPT showed similar test-retest reliability at 1-week and 1-year follow-up to other neuropsychological tests (r = 0.71-0.84 for MCI and 0.53-0.72 for controls). Diagnostic accuracy was modest for this sample (areas under the receiver operating characteristic curve between 0.64 and 0.66). Preliminary psychometric analyses support further study of the IFIPT. The measure showed evidence of clinical utility by demonstrating group differences between this sample of healthy adults and those with MCI.

Structural magnetic resonance imaging (MRI) studies of the human brain have reported evidence for sexual dimorphism. In addition to sex differences in overall cerebral volume, differences in the proportion of gray matter (GM) to white matter (WM) volume have been observed, particularly in the parietal lobe. To our knowledge there have been no studies examining the relationship between the sex differences in parietal lobe structure and function. The parietal lobe is thought to be involved in spatial ability, and particularly involved in mental rotation. The purpose of this study is to examine whether sex differences in parietal lobe structure are present, and if present to relate these differences to performance on the mental rotations test (MRT). We found that women had proportionately greater gray matter volume in the parietal lobe compared to men, and this morphologic difference was disadvantageous for women in terms of performance on the MRT. In contrast, we found that men compared to women had proportionately greater parietal lobe surface area, and this morphologic difference was associated with a performance advantage for men on mental rotation. These findings support the possibility that the sexual dimorphism in the structure of the parietal lobe is a neurobiological substrate for the sex difference in performance on the mental rotations test.

The original structure of the RBANS includes five Indexes; however, recent factor analyses support a two-factor solution (Duff et al., 2006; Wilde, 2006). Unfortunately, normative and psychometric data do not currently exist on these two new Indexes. Building on prior work, the current study provides age- and education-corrected normative data to calculate the factor-derived Verbal and Visual RBANS Indexes (Duff et al., 2006) in a large cohort (n = 718) of older adult primary care patients. Psychometric data (e.g., discrepancy scores, internal consistency, retest reliability) on these new Indexes are also presented. These data might allow clinicians and researchers to better assess laterality effects of brain dysfunction when using the RBANS, although clinical validation is needed.

Executive function and denial of illness were examined among 24 patients who received double-blind antidepressant treatment following stroke. Between end-of-treatment at 3 months and follow-up at 2 years, significant correlation was found between improvement in executive function and decrease in denial of illness.

Objective: Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington's disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease., Method: The goal of this study was to assess OCS in 300 pre-HD individuals and 108 non-gene-expanded controls from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study (enrolled between November 2002 and April 2007) using a multidimensional, self-report measure of OCS, the Schedule of Compulsions, Obsessions, and Pathologic Impulses (SCOPI). Additionally, pre-HD individuals were classified into 3 prognostic groups on the basis of age and CAG repeat length as "near-to-onset" (< 9 estimated years to onset), "mid-to-onset" (9-15 years to onset), and "far-to-onset" (> 15 years to onset). We compared the 3 pre-HD groups to the controls on SCOPI total score and 5 subscales (checking, cleanliness, compulsive rituals, hoarding, and pathologic impulses), controlling for age and gender., Results: All models showed a significant (p < .05) group effect except for hoarding, with an inverted-U pattern of increasing symptoms: controls < far-to-onset < mid-to-onset, with the near-to-onset group being similar to controls. Although the mid-to-onset group showed the most pathology, mean scores were below those of patients with diagnosed obsessive-compulsive disorder. SCOPI items that separated pre-HD individuals from controls were focused on perceived cognitive errors and obsessive worrying., Conclusion: Subclinical OCS were present in pre-HD participants compared to controls. The OCS phenotype in pre-HD may present with obsessive worrying and checking related to cognitive errors and may be a useful target for clinical screening as it could contribute to functional status., (Copyright 2008 Physicians Postgraduate Press, Inc.)

Background: Practice effects have been widely reported in healthy older adults, but these improvements due to repeat exposure to test materials have been more equivocal in individuals with mild cognitive impairment (MCI)., Methods: The current study examined short-term practice effects in MCI by repeating a brief battery of cognitive tests across one week in 59 older adults with amnestic MCI and 62 intact older adults., Results: Participants with amnestic MCI showed significantly greater improvements on two delayed recall measures (p < 0.01) compared to intact peers. All other practice effects were comparable between these two groups. Practice effects significantly improved scores in the MCI group so that 49% of them were reclassified as "intact" after one week, whereas the other 51% remained "stable" as MCI. Secondary analyses indicated the MCI-Intact group demonstrated larger practice effects on two memory measures than their peers (p < 0.01)., Conclusions: These results continue to inform us about the nature of memory deficits in MCI, and could have implications for the diagnosis and possible treatment of this amnestic condition.

Background: This study evaluated brain volumes in healthy older subjects without dementia who presented with memory complaints. The objective was to examine cortical volumes in relation to cognitive performance among patients who do not have dementia, but who do have mild cognitive deficits., Methods: Fifteen participants were evaluated (mean age = 71.8 +/- 6.2). Brain structure was measured via high-resolution magnetic resonance imaging to quantify gray and white matter volumes. Volumetric measures were assessed relative to cognitive function in separate regression models controlling for total cerebral volume. Reported here are measures of global cognitive performance using the Mattis Dementia Rating Scale (DRS) in relation to volumetric measures., Results: Baseline MMSE scores ranged from 27 to 30 (mean = 29.3; SD = 0.9). After controlling for total cerebral volume, we observed that lower white matter volume in the temporal lobe [F(1,14) = 5.72, p = 0.03] was associated with lower performance on the Mattis Dementia Rating Scale (DRS)., Conclusions: Structural imaging may help provide useful clinical information in the context of mild cognitive decline. Currently, the diagnosis of dementia relies on longitudinal measures of cognition. Future studies will help determine whether the addition of brain imaging may enhance diagnostic certainty as well as predict long-term outcome.