Investigating the Factor Structure of the Preclinical Alzheimer Cognitive Composite and Cognitive Function Index across Racial/Ethnic, Sex, and Aß Status Groups in the A4 Study.

BACKGROUND: Disparities in Alzheimer's disease (AD) are well-documented among different racial/ethnic groups and between sex/genders. Neuropsychological assessment provides important information about cognitive changes and can offer valuable insights into disparities. However, neuropsychological measures must be comparable across racial/ethnic and sex/gender groups to accurately interpret disparities. OBJECTIVES: To evaluate measurement invariance (equivalence) of the Preclinical Alzheimer Cognitive Composite (PACC) and the Cognitive Function Index across racial/ethnic, sex/gender, and ß-amyloid (Aß) status groups. DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) Study. The study enrolled participants aged 65-85 from sites across the United States, Canada, Australia, and Japan. MEASUREMENTS: Participants completed the PACC and the Cognitive Function Index. Participants classified as cognitively normal also underwent a Positron Emission Tomography (PET) scan to determine Aß status. RESULTS: Participants self-identified as non-Hispanic White (n=5241), non-Hispanic Black (n=267), Asian (n=228), or Hispanic White (n=225) as well as male (n=2885) or female (n=3076). Among those who underwent a PET scan, 3115 were classified as Aß- and 1309 were classified as Aß+. We found support for a one-factor model for both the PACC and Cognitive Function Index across the full sample and in samples stratified by race/ethnicity, sex/gender, and Aß status. The one-factor model of the PACC and Cognitive Function Index demonstrated scalar measurement invariance across racial/ethnic, sex/gender, and Aß status groups. CONCLUSIONS: Our findings suggest that performance on the PACC and Cognitive Function Index can be compared across the racial/ethnic, sex/gender, and Aß status groups examined in this study.

Dynamics between psychological distress and body mass index throughout adult life; evidence from 3 large cohort studies.

BACKGROUND: Associations between body mass index (BMI) and psychological distress (PD) have been reported; however, few longitudinal studies have accounted for likely life-course differences in BMI and PD stability, consistency, and their interplay across time. METHODS: Via random intercepts cross-lagged panel models, we assessed the predictive effects (from BMI to PD or vice-versa) across the last two centuries in the Coronary Artery Risk Development in Young Adults [CARDIA, beginning in 1985-6] study using the Center for Epidemiological Studies-Depression Scale [CES-D], and in the National Child Development Study [NCDS, beginning in 1958] and British Cohort Study [BCS, beginning in 1970] using the Malaise Inventory [MI]), assessed at least 4 times in adult life. FINDINGS: In CARDIA (n = 4724), NCDS58 (n = 7149) and BCS70 (n = 5967), autoregressive effects were stronger for BMI than for PD, meaning that carry-over effects from one occasion to the next were larger for BMI than for PD. Small interindividual correlations between traits of higher BMI and higher PD were identified among females (rfemale<|0·2|) but not males (rmale<|0·03|) in CARDIA and NCDS. Cross-lagged effects were very weak or close to zero (standardized effects η<|0·1|). INTERPRETATION: In the United States, depressive symptoms and BMI were positively correlated at the trait level among females. In the United Kingdom, relationships between PD and BMI were inconsistent between generations, with effect sizes of unlikely clinical importance, indicating negligible dominance of an intraindividual effect of BMI on PD or vice versa.

Disentangling trait, occasion-specific, and accumulated situational effects of psychological distress in adulthood: evidence from the 1958 and 1970 British birth cohorts.

BACKGROUND: The trajectories of psychological distress differ between individuals, but these differences can be difficult to understand because the measures contain both consistent and situational features; however, in longitudinal studies these sources of information can be disentangled. In addition to occasion-specific features, interindividual differences can be decomposed into two sources of information: trait and carry-over effects between neighboring occasions that are not related to the trait (i.e. accumulated situational effects). METHODS: To disentangle these three sources of variance throughout adulthood, the consistency (trait and accumulated situational effects) and occasion specificity of nine indicators of psychological distress from the Malaise Inventory were examined in two birth cohorts, the 1958 National Child Development Study (NCDS58), and the 1970 British Cohort Study (BCS70). RESULTS: The scale was administered at ages 23, 33, 42, and 50 in NCDS58 (n = 7147), and at ages 26, 30, 34, and 42 in BCS70 (n = 6859). For each psychological symptom, more variance was consistent than occasion-specific. The majority of the consistency was due to trait variance as opposed to accumulated situational effects, indicating that an individual predisposed to be distressed at the beginning of the study remained more likely to be distressed over the whole period. Symptoms of rage were notably more consistent among males than females in both cohorts (78.1% and 81.3% variance explained by trait in NCDS58 and BCS70, respectively), and among females in the NCDS58 (69%). CONCLUSIONS: Symptoms of psychological distress exhibited high stability throughout adulthood, especially among men, due mostly to interindividual trait differences.

Lower serum osteocalcin concentrations in patients with type 2 diabetes and relationships with vascular risk factors among patients with coronary artery disease.

BACKGROUND: Lower serum concentrations of the osteoblast-derived protein, osteocalcin, have been associated with poorer glycemic control, insulin resistance and atherosclerosis, and with the development of type 2 diabetes (T2DM). METHODS: This study compares concentrations of two physiological forms of osteocalcin, carboxylated (cOCN) and uncarboxylated (unOCN), between participants with T2DM (n = 20) and age-, gender- and body mass index (BMI)-matched participants without T2DM (n = 40) among patients with coronary artery disease (CAD), and it explores relationships between osteocalcin concentrations and cardiovascular risk factors. RESULTS: Concentrations of unOCN (2.71 ±â€¯1.86 vs. 4.70 ±â€¯2.03 ng/mL; t = -3.635, p = 0.001) and cOCN (8.70 ±â€¯2.27 vs. 10.77 ±â€¯3.69 ng/mL; t = -2.30, p = 0.025) were lower in participants with T2DM. In participants without T2DM, concentrations of cOCN were associated with fitness (VO2Peak rho = 0.317, p = 0.047) and lower body fat (rho = -0.324, p = 0.041). In participants with T2DM, lower unOCN was associated with HbA1c (rho = -0.516, p = 0.020). Higher body mass was associated with higher unOCN (rho = 0.423, p = 0.009) in participants without T2DM, but with lower concentrations of both unOCN (rho = -0.590, p = 0.006) and cOCN (rho = -0.632, p = 0.003) in participants with T2DM. CONCLUSION: In patients with CAD, lower osteocalcin concentrations were related to type 2 diabetes, and to adverse fitness, metabolic and obesity profiles.

Metabolic/inflammatory/vascular comorbidity in psychiatric disorders; soluble epoxide hydrolase (sEH) as a possible new target.

The common and severe psychiatric disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are associated with inflammation, oxidative stress and changes in peripheral and brain lipid metabolism. Those pathways are implicated in the premature development of vascular and metabolic comorbidities, which account for considerable morbidity and mortality, including increased dementia risk. During endoplasmic reticulum stress, the soluble epoxide hydrolase (sEH) enzyme converts anti-inflammatory fatty acid epoxides generated by cytochrome p450 enzymes into their corresponding and generally less anti-inflammatory, or even pro-inflammatory, diols, slowing the resolution of inflammation. The sEH enzyme and its oxylipin products are elevated post-mortem in MDD, BD and schizophrenia. Preliminary clinical data suggest that oxylipins increase with symptoms in seasonal MDD and anorexia nervosa, requiring confirmation in larger studies and other cohorts. In rats, a soluble sEH inhibitor mitigated the development of depressive-like behaviors. We discuss sEH inhibitors under development for cardiovascular diseases, post-ischemic brain injury, neuropathic pain and diabetes, suggesting new possibilities to address the mood and cognitive symptoms of psychiatric disorders, and their most common comorbidities.

Poor stimulus discriminability as a common neuropsychological deficit between ADHD and reading ability in young children: a moderated mediation model.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is frequently associated with poorer reading ability; however, the specific neuropsychological domains linking this co-occurrence remain unclear. This study evaluates information-processing characteristics as possible neuropsychological links between ADHD symptoms and RA in a community-based sample of children and early adolescents with normal IQ (⩾70). METHOD: The participants (n = 1857, aged 6-15 years, 47% female) were evaluated for reading ability (reading single words aloud) and information processing [stimulus discriminability in the two-choice reaction-time task estimated using diffusion models]. ADHD symptoms were ascertained through informant (parent) report using the Development and Well-Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards), visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic status, and IQ were included as covariates. RESULTS: In a moderated mediation model, stimulus discriminability mediated the effect of ADHD on reading ability. This indirect effect was moderated by age such that a larger effect was seen among younger children. CONCLUSION: The findings support the hypothesis that ADHD and reading ability are linked among young children via a neuropsychological deficit related to stimulus discriminability. Early interventions targeting stimulus discriminability might improve symptoms of inattention/hyperactivity and reading ability.

Depressive symptoms predict non-completion of a structured exercise intervention for people with Type 2 diabetes.

AIM: To quantify the impact of depressive symptoms on completion of exercise-based rehabilitation for Type 2 diabetes management. METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale in a prospective cohort of consecutive patients with Type 2 diabetes entering a 6-month hybrid (home- and clinic-based) exercise rehabilitation programme. Attendance at exercise sessions was monitored and programme completion/non-completion was ascertained. RESULTS: Of the programme participants (n=624, mean age 55.6±10.5 years, 47% male), 26.8% endorsed significant depressive symptoms (depression score ≥16) and 68.1% completed the intervention, attending 54.6±30.0% of supervised exercise sessions. Baseline depressive symptoms (depression scale score ≥16) increased the risk of non-completion [hazard ratio 1.49 (95% CI 1.10-2.03); P = 0.010], and predicted fewer sessions attended (ß=-2.1, P= 0.002) in adjusted models. A depression score threshold of ≥10 (48.4% of participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P= 0.002) with optimum accuracy. Non-completions resulting from lack of interest (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006) were more common among participants with depression scores ≥10. Greater hazard ratios for depression scores ≥10 were observed in subgroups not currently using insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. CONCLUSIONS: Depressive symptoms were highly prevalent among participants with Type 2 diabetes entering exercise-based rehabilitation, and even mild depressive symptoms posed a significant barrier to completion. Depression screening may help target additional supports to facilitate completion of exercise interventions for people with Type 2 diabetes.

Regional cerebral arterial transit time hemodynamics correlate with vascular risk factors and cognitive function in men with coronary artery disease.

BACKGROUND AND PURPOSE: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. MATERIALS AND METHODS: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. RESULTS: Principal component analysis identified 2 components of vascular risk: 1) "pressor" (age, systolic blood pressure, and pulse pressure) and 2) "obesity" (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r(2) = 0.21, t = -2.65, P = .01). CONCLUSIONS: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.

Quality of life and psychosocial measures influenced by exercise modality in patients with coronary artery disease.

BACKGROUND: The optimal approach to prescribing resistance training (RT) combined with aerobic training (AT) for psychosocial and health-related quality of life (HRQOL) is unclear. AIM: To compare the effects of AT combined with RT (1 versus 3 sets) versus AT alone on HRQOL and psychosocial outcomes. DESIGN: Subjects (N.=72) were randomized to AT (5 d∙wk-1) or AT (3 d∙wk-1) with either 1 set (AT/RT1) or 3 sets (AT/RT3) of RT performed 2 d∙wk-1. SETTING: Outpatient Cardiac Rehabilitation Program. POPULATION: Subjects with coronary artery disease. METHODS: HRQOL and psychosocial parameters were assessed before and after 29 weeks of training by questionnaire. RESULTS: Fifty-three subjects (mean±SD age 60.6±10.6 years) completed training. There was a group effect for change in self-efficacy of lower body physical activity tasks (P=0.03) with significantly greater improvement for AT/RT3 than AT alone (17.5±16.6% vs. 3.2±12.8% respectively, p=0.04). Lower body self-efficacy improved for AT/RT1 (15.5±13.8%, p<0.001) but not for AT alone (P=0.2). Self-efficacy for upper body tasks improved with AT/RT3 (18.2±19.9%, P=0.003) and AT/RT1 training (12.6±15.8%, P=0.005) but not with AT alone (8.3±16.1%, P=0.1). AT/RT3 and AT/RT1 training yielded improvements in depression score (-4.0±7.7, P=0.04 and -3.0±5.1, P=0.02 respectively) but not with AT alone (-0.5±4.7, P=0.71). The improvement from baseline in physical HRQOL score (MOS, SF-36) averaged 8.2±11.2% for AT (P=0.04), 10.4±11.9% for AT/RT1 (P=0.006) and 12.0±12.9% for AT/RT3 (P=0.004). CONCLUSIONS: Both AT+RT groups with either 1 or 3 sets (AT 3 d∙wk-1and RT 2 d∙wk-1) each yield more pronounced psychosocial and HRQOL adaptations than AT alone (5 d∙wk-1). RT prescription beyond 1 set may further augment selected parameters in cardiac patients. CLINICAL REHABILITATION IMPACT: These results provide further rationale to develop combined AT+RT regimens for individuals with coronary artery disease.

Poststroke neuropsychiatric symptoms: relationships with IL-17 and oxidative stress.

Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female), 19 had depressive symptoms (CES-D ≥ 16), which was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17 concentrations did not differ between subjects with and without depressive symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004). In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ = 0.518, P = 0.023) and lower IL-10 (ρ = -0.484, P = 0.036), but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.

Brain derived neurotrophic factor, cardiopulmonary fitness and cognition in patients with coronary artery disease.

OBJECTIVE: To assess serum brain derived neurotrophic factor (BDNF) concentrations as a correlate of cardiopulmonary fitness and as a predictor of cognitive performance in subjects with coronary artery disease (CAD). METHODS: Serum BDNF concentrations were assayed by ELISA and fitness was assessed using a standardized exercise stress test. The Mini Mental Status Examination (MMSE), California Verbal Learning Test 2nd Ed., Stroop, Trail Making Test B and the Digit Symbol-Coding task were administered. The val66met BDNF genotype and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined as potential confounders. RESULTS: In subjects with CAD (n=88; 85.2% male, mean age 62.8±10.5 yr), cardiopulmonary fitness was associated with higher serum BDNF concentrations (ß=.305, p=.013). Higher serum BDNF concentrations were associated with higher MMSE scores (F(1,87)=15.406, p<.0005) and better performance on the Digit Symbol-Coding task (F(1,87)=9.620, p=.003). IL-6, TNF-α and the val66met genotype did not influence these results. CONCLUSION: Serum BDNF concentrations were associated with cardiopulmonary fitness, psychomotor processing speed and overall cognition in subjects with CAD.