Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.

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.

Cognitive function and its relationship with brain structure in myotonic dystrophy type 1.

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.

Comparison of T1Rho MRI, Glucose Metabolism, and Amyloid Burden Across the Cognitive Spectrum: A Pilot Study.

OBJECTIVE: The pathological cascades associated with the development of Alzheimer's disease (AD) have a common element: acidosis. T1rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T1rho 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 (T1-weighted and T1rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([11C]Pittsburg compound B for amyloid burden [N=26] and [18F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T1rho values and neuropsychological, demographic, and imaging measures were explored. RESULTS: Global mean and median T1rho were positively associated with age. After controlling for age, higher global T1rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T1rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions. CONCLUSIONS: Higher T1rho values were associated with greater cognitive impairment and pathological burden. T1rho, 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.

Reduced Attention in Former Smokers with and without COPD.

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.

Long-Term Cognitive and Psychological Functioning in Post-Electroconvulsive Therapy Patients.

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.

Prevention of post-stroke generalized anxiety disorder, using escitalopram or problem-solving therapy.

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.

Association of anxiety with resistance vessel dysfunction in human atherosclerosis.

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: ß = -.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: ß = -.175, p = .060; BMI: ß = -.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.

Incident apathy during the first year after stroke and its effect on physical and cognitive recovery.

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.

Prevention of poststroke apathy using escitalopram or problem-solving therapy.

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.

White matter fractional anisotropy is inversely related to anxious symptoms in older adults with atherosclerosis.

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.

Anxious symptoms and cognitive function in non-demented older adults: an inverse relationship.

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.

Patterns of serotonergic antidepressant usage in prodromal Huntington disease.

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.

Increased frequency of first-episode poststroke depression after discontinuation of escitalopram.

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.

Practice effects predict cognitive outcome in amnestic mild cognitive impairment.

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.

Influence of education on subcortical hyperintensities and global cognitive status in vascular dementia.

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.

The RBANS Effort Index: base rates in geriatric samples.

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.

DMPK mRNA Expression in Human Brain Tissue Throughout the Lifespan.

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.

Cognitive Deficits, Apathy, and Hypersomnolence Represent the Core Brain Symptoms of Adult-Onset Myotonic Dystrophy Type 1.

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.

Cognitive performance is lower among individuals with overlap syndrome than in individuals with COPD or obstructive sleep apnea alone: association with carotid artery stiffness.

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 FEV1/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 ß-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 FEV1/FVC. Higher CCA ß-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.

Daily Activities: The Impact of COPD and Cognitive Dysfunction.

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.