Depression predicts cognitive and functional decline one month after coronary artery bypass graft surgery (Neuropsychiatric Outcomes After Heart Surgery study).

BACKGROUND: Prior research on cognitive and functional outcomes after coronary artery bypass graft (CABG) surgery has largely explored these two domains in isolation. In this study, we assess baseline depression and cognition as risk factors for decline in the Clinical Dementia Rating Sum-of-Boxes (CDR-SB) 1 month post-CABG surgery, which a combined measure of cognition and function. DESIGN: The Neuropsychiatric Outcomes After Heart Surgery study is a prospective observational cohort study. SETTING: A tertiary care, academic center. PARTICIPANTS: Of a total study sample of 148 patients undergoing CABG surgery, 124 (83.8%) completed 1-month follow-up assessment. Mean age was 66.3, 32 (25.8%) female and 112 (90.3%) White. MEASUREMENTS: Cognition, function, and depression were assessed on semi-structured clinical interviews. Cognitive and functional status were defined using CDR-SB; mild or major depression was defined by the Hamilton Depression Rating Scale. Additionally, neuropsychological battery was performed at baseline. RESULTS: CDR-SB decline occurred in 18 (14.5%) subjects. Older age, depression, baseline CDR-SB, and postoperative delirium were associated with 1-month decline on univariate analysis. Older age (OR 1.1 [1.0-1.2]) and depression (OR 6.2 [1.1-35.0]) remained significant on multivariate regression. In separate models, baseline performance on visual Wechsler memory scale (delayed), Hopkins verbal learning test (immediate and delayed), controlled oral word fluency test, and Trails B predicted CDR-SB decline. CONCLUSION: Roughly one in seven patients experienced CDR-SB decline 1 month after CABG surgery. Also, preoperative depression deserves recognition for being a predictor of CDR-SB decline one month post-CABG.

Depression Predicts Delirium After Coronary Artery Bypass Graft Surgery Independent of Cognitive Impairment and Cerebrovascular Disease: An Analysis of the Neuropsychiatric Outcomes After Heart Surgery Study.

OBJECTIVE: Although depression is a known risk factor for delirium after coronary artery bypass graft (CABG) surgery, it is unclear whether this risk is independent of delirium risk attributable to cognitive impairment or cerebrovascular disease. This study examines depression, mild cognitive impairment (MCI), and cerebrovascular disease as post-CABG delirium risk factors. METHODS: This prospective observational cohort study was performed in a tertiary-care academic hospital. Subjects were without dementia and undergoing CABG surgery. Preoperative cognitive assessment included Clinical Dementia Rating and neuropsychological battery; depression was assessed using Depression Interview and Structured Hamilton. Baseline intracranial stenosis was evaluated by transcranial Doppler of bilateral middle cerebral arteries (MCAs). Study psychiatrists assessed delirium on postoperative days 2-5 using the Confusion Assessment Method. RESULTS: Our analytic sample comprised 131 subjects (average age: 65.8 ± 9.2years, 27% women). MCI prevalence was 24%, preoperative depression 10%, lifetime depression 35%, and MCA stenosis (≥50%) 28%. Sixteen percent developed delirium. Multivariate analysis revealed that age, MCI (odds ratio [OR]: 5.1; 95% confidence interval [CI]: 1.3-20.1), and preoperative depression (OR: 9.9; 95% CI: 1.3-77.9)-but not lifetime depression-predicted delirium. MCA stenosis and severity predicted delirium in univariate but not multivariate analysis. Right MCA stenosis severity predicted delirium severity, but left-sided stenosis severity did not. CONCLUSION: We established that the risk of delirium attributable to depression extends beyond the potential moderating influence of cognitive impairment and cerebrovascular disease alone. Even mild depression and cognitive impairment before CABG deserve recognition for their effect on post-CABG cognitive health.

The effect of age and smoking on the hippocampus and memory in late middle age.

From middle age the hippocampus atrophies at an accelerating rate. Factors that further this acceleration may hasten memory decline and the onset of memory disorder. We studied associations between smoking history, age, ApoE e4 genotype, vascular risk factors, hippocampal volume, and cognition in 67 middle-aged subjects (mean age = 56 years) who were offspring of parents with dementia. Subjects underwent isotropic T1-weighted 3 T MRI brain scanning with FreeSurfer volumetric data extraction for the hippocampus, a neuropsychological assessment battery, extensive medical data collection, and ApoE genotyping. ApoE e4, vascular risk variables, and alcohol history were unrelated to hippocampal volume. Hippocampal volume correlated negatively with age and positively with memory performance, but not with global cognition. Aging diminished hippocampal volume by 0.52% per year. Female subjects (only two males smoked) with a heavy smoking history (≥ 9.5 pack-years; n = 11) exhibited hippocampal volumes that were 7.4% smaller than the volumes of females (n = 37) with a light or no smoking history. In our sample by late middle age, a history of moderate to heavy smoking is associated with hippocampal atrophy equivalent to 12 years of aging. Since only a small number of subjects within the sample have a smoking history, validation of this finding in larger samples is desirable.

Cognition and the course of prodromal Parkinson's disease.

BACKGROUND: Prospective data on cognition in prodromal Parkinson's disease are limited. The objectives of this study were to assess in prodromal PD (1) if baseline cognition predicts conversion to clinical PD, (2) if baseline dopamine transporter binding predicts longitudinal changes in cognition, and (3) if impaired olfaction predicts future cognitive decline. METHODS: Prodromal participants were 136 hyposmic individuals enrolled in the Parkinson Associated Risk Study. We examined baseline neuropsychological test performance in PD converters versus nonconverters and the association between baseline dopamine transporter binding and change in cognition. An additional 73 normosmic individuals were included in analyses of the relationship between hyposmia and cognitive decline. RESULTS: In prodromal participants, baseline cognitive scores did not significantly predict conversion, but converters performed numerically worse on 5 of the 6 cognitive domains assessed, with the greatest differences in executive function/working memory (0.68 standard deviation lower) and global cognition (0.64 standard deviation lower). Lower baseline dopamine transporter binding predicted greater future decline in processing speed/attention (P = 0.02). Hyposmia predicted greater future decline in language (P = 0.005) and memory (P = 0.01) abilities. CONCLUSIONS: Given hyposmia in the general population predicts cognitive decline, the role of cognition in predicting conversion in prodromal PD needs to be assessed in large cohorts followed long-term. The dopamine system may be associated with changes in processing speed/attention in individuals at risk for PD. © 2017 International Parkinson and Movement Disorder Society.

Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.

Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.

Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings.

OBJECTIVES: The Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort. METHODS: Individuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normative scores created for global cognition, memory, executive function/working memory, processing speed/attention, visuospatial abilities, and language domains. Other non-motor symptoms (constipation, depression, anxiety, and rapid eye movement sleep behavior disorder) were assessed through questionnaires. RESULTS: Individuals with both hyposmia and reduced dopamine transporter binding (n = 38) had lower mean scores for global cognition, executive function/working memory, and memory compared with all other participants (n = 187). In separate multivariate logistic regression models, lower global cognition (odds ratio, 1.97, P = 0.004), and specifically executive function/working memory (odds ratio, 1.84, P = 0.004) scores were associated with membership in the hyposmia with dopamine transporter reduction group. Combining hyposmia with relative impairment on specific cognitive domains increased the odds of dopamine transporter binding reduction compared with hyposmia alone, with the greatest increase in odds for hyposmia plus executive function/working memory relative impairment (68% increase in odds from 4.14 to 6.96). CONCLUSION: Changes in global cognitive abilities, and specifically executive function/working memory, are present in individuals at risk for PD. Combining non-motor features, including cognition, improves prediction of dopamine transporter binding reduction.

Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease.

UNLABELLED: This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD). BACKGROUND: Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS. METHODS: Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy. RESULTS: Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P < 0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P < 0.001) and apathy (P < 0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P = 0.51). CONCLUSIONS: Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS. © 2015 International Parkinson and Movement Disorder Society.

Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study.

BACKGROUND: Cognitive and functional impairment increase risk for post-coronary artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is necessary to increase PCD risk remains unclear. METHODS: The Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort study of participants undergoing elective CABG surgery. Pre-operative cognitive and functional status based on Clinical Dementia Rating (CDR) scale and neuropsychological battery are assessed. We defined mild cognitive impairment (MCI) based on either (1) CDR global score 0.5 (CDR-MCI) or (2) performance 1.5 SD below population means on any cognitive domain on neurocognitive battery (MCI-NC). Delirium was assessed daily post-operative day 2 through discharge using the confusion assessment method (CAM) and delirium index (DI). We investigate whether MCI - either definition - predicts delirium or delirium severity. RESULTS: So far we have assessed 102 participants (mean age 65.1 ± 9; male: 75%) for PCD. Twenty six participants (25%) have MCI-CDR; 38 (62% of those completing neurocognitive testing) met MCI-NC criteria. Fourteen participants (14%) developed PCD. After adjusting for age, sex, comorbidity, and education, MCI-CDR, MMSE, and Lawton IADL score predicted PCD on logistic regression (OR: 5.6, 0.6, and 1.5, respectively); MCI-NC did not (OR [95% CI]: 11.8 [0.9, 151.4]). Using similarly adjusted linear regression, MCI-CDR, MCI-NC, CDR sum of boxes, MMSE, and Lawton IADL score predicted delirium severity (adjusted R(2): 0.26, 0.13, 0.21, 0.18, and 0.32, respectively). CONCLUSIONS: MCI predicts post-operative delirium and delirium severity, but MCI definition alters these relationships. Cognitive and functional impairment independently predict post-operative delirium and delirium severity.

Age-related, multivariate associations between white matter microstructure and behavioral performance in three executive function domains.

The executive function (EF) domains of working memory (WM), response inhibition (RI), and set shifting (SS) show maturational gains and are linked to neuroimaging-measured brain changes. This study explored ways in which maturation-linked differences in EF abilities are systematically associated with white matter microstructural differences from adolescence into young adulthood. Diffusion tensor imaging (DTI) and nine neurocognitive tests were collected from 120 healthy subjects ages 12-24. Analyses across the white matter skeleton were performed, focusing on fractional anisotropy (FA). Data were 'fused' using a multivariate technique (CCA+jICA), producing four independent components (ICs) depicting white matter FA values that covaried with test performance. Correlations between age and IC loading coefficients identified three EF-DTI profiles that may change developmentally. In one, SS performance was linked to greater reliance on the FA of ventral brain tracts, and less on dorsal tracts with age. In another, white matter microstructure was related to a pattern of strong WM and weak SS that became more pronounced with age. A final IC revealed that younger individuals with low RI and high WM/SS skills typically matured out of this cognitive imbalance, underscored by white matter changes with age. These novel multivariate results begin to emphasize the complexity of brain structure-cognition relationships in adolescents and young adults.

Impaired olfaction and other prodromal features in the Parkinson At-Risk Syndrome Study.

To test the association between impaired olfaction and other prodromal features of PD in the Parkinson At-Risk Syndrome Study. The onset of olfactory dysfunction in PD typically precedes motor features, suggesting that olfactory testing could be used as a screening test. A combined strategy that uses other prodromal nonmotor features, along with olfactory testing, may be more efficient than hyposmia alone for detecting the risk of PD. Individuals with no neurological diagnosis completed a mail survey, including the 40-item University of Pennsylvania Smell Identification Test, and questions on prodromal features of PD. The frequency of reported nonmotor features was compared across individuals with and without hyposmia. A total of 4,999 subjects completed and returned the survey and smell test. Of these, 669 were at or below the 15th percentile based on age and gender, indicating hyposmia. Hyposmics were significantly more likely to endorse nonmotor features, including anxiety and depression, constipation, and rapid eye movement sleep behavior disorder symptoms, and to report changes in motor function. Twenty-six percent of subjects with combinations of four or more nonmotor features were hyposmic, compared to 12% for those reporting three or fewer nonmotor features (P < 0.0001). Hyposmia is associated with other nonmotor features of PD in undiagnosed individuals. Further assessment of hyposmic subjects using more specific markers for degeneration, such as dopamine transporter imaging, will evaluate whether combining hyposmia and other nonmotor features is useful in assessing the risk of future neurodegeneration.

Age and gender but not common chronic illnesses predict odor identification in older African Americans.

OBJECTIVES: Loss of smell accompanies specific neurodegenerative diseases and may facilitate the early detection of these. Smell deficiency also engenders safety risks in the elderly. The Brief Smell Identification Test (BSIT), though clinically practical, is accompanied by limited normative data, and none for minority subjects. We sought to improve the clinical utility of the BSIT by determining the relationship between test score, demographics, and chronic illnesses in a minority cohort. DESIGN: We evaluated BSIT performance in a cohort of cognitively healthy older African Americans and compared our findings with all existing data for the test. SETTING: General community. PARTICIPANTS: African Americans (N = 288) age 55-87 years living independently. MAIN OUTCOME MEASURE: BSIT score stratified by demographic predictors. RESULTS: Age and gender were predictive of score, but education, global cognition, hypertension, diabetes, and thyroid disorder were not significantly related to performance within this cognitively healthy sample. Comparison of our findings with international studies suggests reasonably consistent performance levels across diverse samples. CONCLUSIONS: The lack of a significant relationship between common chronic conditions, or sociocultural factors, with the BSIT score underscores the value of this test in screening for odor identification deficiencies in older subjects.

Neuropsychiatric symptoms and cognitive abilities over the initial quinquennium of Parkinson disease.

OBJECTIVE: To determine the evolution of numerous neuropsychiatric symptoms and cognitive abilities in Parkinson disease from disease onset. METHODS: Prospectively collected, longitudinal (untreated, disease onset to year 5), observational data from Parkinson's Progression Markers Initiative annual visits was used to evaluate prevalence, correlates, and treatment of 10 neuropsychiatric symptoms and cognitive impairment in Parkinson disease participants and matched healthy controls. RESULTS: Of 423 Parkinson disease participants evaluated at baseline, 315 (74.5%) were assessed at year 5. Eight neuropsychiatric symptoms studied increased in absolute prevalence by 6.2-20.9% at year 5 relative to baseline, and cognitive impairment increased by 2.7-6.2%. In comparison, the frequency of neuropsychiatric symptoms in healthy controls remained stable or declined over time. Antidepressant and anxiolytic/hypnotic use in Parkinson disease were common at baseline and increased over time (18% to 27% for the former; 13% to 24% for the latter); antipsychotic and cognitive-enhancing medication use was uncommon throughout (2% and 5% of patients at year 5); and potentially harmful anticholinergic medication use was common and increased over time. At year 5 the cross-sectional prevalence for having three or more neuropsychiatric disorders/cognitive impairment was 56% for Parkinson disease participants versus 13% for healthy controls, and by then seven of the examined disorders had either occurred or been treated at some time point in the majority of Parkinson disease patients. Principal component analysis suggested an affective disorder subtype only. INTERPRETATION: Neuropsychiatric features in Parkinson disease are common from the onset, increase over time, are frequently comorbid, and fluctuate in severity.

Endophenotypes in schizophrenia: a selective review.

BACKGROUND: Given the wealth of data in the literature on schizophrenia endophenotypes, it is useful to have one source to reference their frequency data. We reviewed the literature on disease-liability associated variants in structural and functional magnetic resonance images (MRI), sensory processing measures, neuromotor abilities, neuropsychological measures, and physical characteristics in schizophrenia patients (SCZ), their first-degree relatives (REL), and healthy controls (HC). The purpose of this review was to provide a summary of the existing data on the most extensively published endophenotypes for schizophrenia. METHODS: We searched PubMed and MedLine for all studies on schizophrenia endophenotypes comparing SCZ to HC and/or REL to HC groups. Percent abnormal values, generally defined as >2 SD from the mean (in the direction of abnormality) and/or associated effect sizes (Cohen's d) were calculated for each study. RESULTS: Combined, the articles reported an average 39.4% (SD=20.7%; range=2.2-100%) of abnormal values in SCZ, 28.1% (SD=16.6%; range=1.6-67.0%) abnormal values in REL, and 10.2% (SD=6.7%; range=0.0-34.6%) in HC groups. CONCLUSIONS: These findings are reviewed in the context of emerging hypotheses on schizophrenia endophenotypes, as well as a discussion of clustering trends among the various intermediate phenotypes. In addition, programs for future research are discussed, as instantiated in a few recent large-scale studies on multiple endophenotypes across patients, relatives, and healthy controls.

Neuropsychological course in the prodrome and first episode of psychosis: findings from the PRIME North America Double Blind Treatment Study.

OBJECTIVE: There is uncertainty regarding the onset timing of the cognitive deficiencies of schizophrenia. We investigated whether conversion to psychosis and/or olanzapine altered the neuropsychological course of subjects within the first-ever double blind medication study of the putative schizophrenia first episode prodrome. METHOD: Sixty participants in a double blind trial of olanzapine as a treatment for putative prodromal states were assessed at entry (pre-randomization), and again at 6 and 12 months (if they remained non-psychotic), or at any of these points prior to psychosis followed by post-psychosis and 6 months post-psychosis assessments. RESULTS: Participants who converted to psychosis did not differ from placebo non-converters in pre-randomization global neuropsychological status. Early converters did not differ from later converters in entry neuropsychological status. Subjects who converted after 6 months did not show neuropsychological declines during the initial, pre-psychosis, 6 months. Neuropsychological course did not differ between converters to psychosis and non-converters, or between olanzapine and placebo-assigned subjects. CONCLUSIONS: Neither the onset of frank psychosis nor olanzapine treatment of the prodrome significantly alters neuropsychological course in persons considered to be at high risk at their initial (pre-psychosis) assessment. These findings suggest that the neuropsychological deficiencies associated with psychotic conditions largely pre-exist the first frank psychotic episode.

Self-reported distress after cognitive testing in patients with Alzheimer's disease.

BACKGROUND: The prevalence and degree of self-reported distress that patients with Alzheimer's disease (AD) experience after cognitive testing remain unknown. It is also unknown whether this level of distress is at all related to specific patient factors, test performance, or awareness of test performance. METHODS: In 154 mild-to-moderate AD patients and 62 cognitively intact patients, we measured self-reported distress, on a five-point Likert scale, after 45 minutes of cognitive testing. Using multivariate logistic regression, we then examined whether demographic factors, level of education, depressive symptoms, cognitive performance, perceived test difficulty, and perceived test performance compared to 10 years ago were predictive of self-reported distress. RESULTS: The prevalence of any self-reported distress in patients with AD was 70% compared to 47% in patients without AD (p <.001). Of persons with AD, bivariate analyses revealed that those who reported more difficulty with testing (relative risk [RR] 1.32; 95% confidence interval [CI], 1.25-1.37) and felt that they performed worse than 10 years ago (RR 1.21; 95% CI, 1.07-1.30) were at increased risk for reporting more distress. Paradoxically, cognitive performance was a weak predictor of distress, with only language performance demonstrating an association (RR 0.95; 95% CI, 0.89-0.99). Adjustments for demographic factors, education, dementia severity, or depressive symptoms in the multivariable analyses did not alter these relationships. CONCLUSION: Cognitive tasks provoke more distress in patients with mild-to-moderate AD compared with persons who do not have dementia. Predictors of distress are more closely related to patient awareness about test difficulty and performance, rather than actual test performance.

Everyday decision-making ability in older persons with cognitive impairment.

OBJECTIVE: To demonstrate the reliability and validity of the Assessment of Capacity for Everyday Decision-Making (ACED), an instrument to evaluate everyday decision-making. METHODS: The authors administered the ACED to 39 persons with very mild to moderate cognitive impairment and 13 cognitively intact caregivers. RESULTS: Intraclass correlation coefficients showed good reliability for the measures of understanding, appreciation and reasoning, and Cronbach's alpha coefficients were > or =0.84 for all three decision-making abilities. The ACED also had a moderate to strong correlation with the MacArthur Competency Assessment Tool for Treatment, a validated measure of decision-making capacity for medical treatment decisions, and measures of overall cognition. Associations with measures of executive function were mixed, with moderate correlations observed only with ACED understanding and reasoning performance. CONCLUSION: The ACED is a reliable and valid measure to assess decision-making capacity. It may serve as an important addition to current methods used to assess everyday decision-making.

A New Measure for Neural Compensation Is Positively Correlated With Working Memory and Gait Speed.

Neuroimaging studies suggest that older adults may compensate for declines in brain function and cognition through reorganization of neural resources. A limitation of prior research is reliance on between-group comparisons of neural activation (e.g., younger vs. older), which cannot be used to assess compensatory ability quantitatively. It is also unclear about the relationship between compensatory ability with cognitive function or how other factors such as physical exercise modulates compensatory ability. Here, we proposed a data-driven method to semi-quantitatively measure neural compensation under a challenging cognitive task, and we then explored connections between neural compensation to cognitive engagement and cognitive reserve (CR). Functional and structural magnetic resonance imaging scans were acquired for 26 healthy older adults during a face-name memory task. Spatial independent component analysis (ICA) identified visual, attentional and left executive as core networks. Results show that the smaller the volumes of the gray matter (GM) structures within core networks, the more networks were needed to conduct the task (r = -0.408, p = 0.035). Therefore, the number of task-activated networks controlling for the GM volume within core networks was defined as a measure of neural compensatory ability. We found that compensatory ability correlated with working memory performance (r = 0.528, p = 0.035). Among subjects with good memory task performance, those with higher CR used fewer networks than subjects with lower CR. Among poor-performance subjects, those using more networks had higher CR. Our results indicated that using a high cognitive-demanding task to measure the number of activated neural networks could be a useful and sensitive measure of neural compensation in older adults.

Longitudinal Effects of Alcohol Consumption on the Hippocampus and Parahippocampus in College Students.

BACKGROUND: The hazardous effects of alcohol consumption on both the hippocampus and memory have been well established. However, the longitudinal effects of ethanol on the developing brain and related consequences on memory are not well explored. Given the above, we investigated the longitudinal effects of college drinking on hippocampal volume in emerging college adults. METHODS: Data were derived from the longitudinal Brain and Alcohol Research with College Students study. A subset of 146 freshmen (mean age at baseline = 18.5 years) underwent brain magnetic resonance imaging scans at baseline and 24 months later. Four drinking-related measures derived from monthly surveys were reduced to a single alcohol use index using principal component analysis. Gray matter volumetric change (GMV-c) data were derived using a longitudinal pipeline. Voxelwise hippocampal/para-hippocampal GMV-c associations with the drinking index were derived using a multiple regression framework within SPM12. Supplementary associations were assessed between GMV-c and memory scores computed from the California Verbal Learning Test-II (assessed at the end of the study), and between GMV-c and total alcohol-induced memory blackouts. RESULTS: Larger alcohol use index was associated with an accelerated GMV decline in the hippocampus/para-hippocampus. Also, larger hippocampal volume decline was associated with poorer memory performance and more memory blackouts. CONCLUSIONS: Our study extends prior cross-sectional literature by showing that a heavier drinking burden while in college is associated with greater hippocampal GMV decline that is in turn associated with poorer memory scores, all of which could ultimately have a significant impact on student success.

Relationship between fMRI response during a nonverbal memory task and marijuana use in college students.

Marijuana (MJ) is widely used among college students, with peak use between ages 18-22. Research suggests memory dysfunction in adolescent and young adult MJ users, but the neural correlates are unclear. We examined functional magnetic resonance imaging (fMRI) response during a memory task among college students with varying degrees of MJ involvement. Participants were 64 college students, ages 18-20, who performed a visual encoding and recognition task during fMRI. MJ use was ascertained for 3 months prior to scanning; 27 individuals reported past 3-month MJ use, and 33 individuals did not. fMRI response was modeled during encoding based on whether targets were subsequently recognized (correct encoding), and during recognition based on target identification (hits). fMRI response in left and right inferior frontal gyrus (IFG) and hippocampal regions of interest was examined between MJ users and controls. There were no group differences between MJ users and controls on fMRI response during encoding, although single sample t-tests revealed that MJ users failed to activate the hippocampus. During recognition, MJ users showed less fMRI response than controls in right hippocampus (Cohen's d = 0.55), left hippocampus (Cohen's d = 0.67) and left IFG (Cohen's d = 0.61). Heavier MJ involvement was associated with lower fMRI response in left hippocampus and left IFG. This study provides evidence of MJ-related prefrontal and hippocampal dysfunction during recognition memory in college students. These findings may contribute to our previously identified decrements in academic performance in college MJ users and could have substantial implications for academic and occupational functioning.

Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial.

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age.