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Hoogendam Y.Y.,Erasmus Medical Center | Van Der Geest J.N.,Neuroscience | Niessen W.J.,Radiology | Niessen W.J.,Erasmus Medical Center | And 4 more authors.
Alzheimer Disease and Associated Disorders | Year: 2014

Background: It is unknown whether the cerebellum affects cognitive function in an aging community-dwelling population. In a population- based study on 3745 nondemented individuals aged 45 years and above, we investigated the relationship between cerebellar volume and cognitive function. Methods: Brain volumes were obtained using automatic tissue segmentation of magnetic resonance imaging scans. Cognitive functioning was assessed using MMSE and cognitive compound scores of global cognition, executive function, information processing speed, memory, and motor speed. Linear regression modeling was used to study the associations between cerebellar volumes and cognitive measures, independent of cerebral volumes. Results: We found a relationship between larger cerebellar volume and better global cognition, executive function, information processing speed, and motor speed. After adjustment for cerebral volume, only cerebellar gray matter volume remained borderline significantly associated with global cognition and information processing speed. After Bonferroni correction, the few associations found between cerebellar volume and cognition disappeared. Conclusions: We only found a minor relationship between larger cerebellar volume and better cognition in healthy older adults, which further attenuated after correcting for cerebral volume. Our findings support the notion that cerebellar volume has an influence on cognition in aging, but that it is not the major leading structure.. Copyright © 2014 by Lippincott Williams &Wilkins.

Wadehra S.,Wayne State University | Pruitt P.,Neuroscience | Murphy E.R.,Georgetown University | Diwadkar V.A.,Wayne State University
Schizophrenia Research | Year: 2013

Schizophrenia (SCZ) is characterized by disordered activation and disordered connectivity, yet few fMRI studies have convergently investigated both. Here, we compared differences in activation and connectivity between SCZ and controls (HC). Twenty-two subjects (18. ≤. age. ≤. 35. yrs) participated in a paired-associative learning task, a behavioral domain particularly dependent on fronto-hippocampal connectivity and of relevance to the schizophrenia diathesis. Activation differences were assessed using standard approaches. Seed-based connectivity differences were compared using Psychophysiological Interaction (PPI) with a hippocampus-based seed. SCZ evinced significantly increased activation, but significantly decreased connectivity with the hippocampus across a cortical-striatal learning network. These results assess potentially complementary patterns of network dysfunction in schizophrenia: increased activation suggests inefficient responses relating to functional specialization; decreased connectivity suggests impaired integration of functional signals between regions. Inefficiency and dysconnection appear to collectively characterize functional deficits in schizophrenia. © 2013 Elsevier B.V.

Popov V.M.,Thomas Jefferson University | Wu K.,Thomas Jefferson University | Zhou J.,Thomas Jefferson University | Powell M.J.,Thomas Jefferson University | And 3 more authors.
Trends in Endocrinology and Metabolism | Year: 2010

The dachshund (dac) gene was initially described as a mutant phenotype in flies featuring extremely short legs relative to their body length. Functioning as a dominant suppressor of the ellipse mutation, a hypermorphic allele of the Epidermal Growth Factor Receptor (EGFR), the dac gene plays a key role in metazoan development, regulating ocular, limb, brain, and gonadal development. In the Drosophila eye, dac is a key component of the Retinal Determination Gene Network (RDGN) governing the normal initiation of the morphogenetic furrow and thereby eye development. Recent studies have demonstrated an important role for human Dachshund homologue (DACH1) in tumorigenesis, in particular, breast, prostate and ovarian cancer. The molecular mechanisms by which DACH1 regulates differentiation and tumorigenesis are discussed herein.

Spencer T.J.,Massachusetts General Hospital | Adler L.A.,New York University | Qiao M.,Lilly United States LLC | Saylor K.E.,Neuroscience | And 5 more authors.
Journal of Attention Disorders | Year: 2010

Objective: Validation of the Adult ADHD Investigator Symptom Rating Scale (AISRS) that measures aspects of ADHD in adults. Method: Psychometric properties of the AISRS total and AISRS subscales are analyzed and compared to the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) and the Clinical Global Impression-ADHD-Severity Scale using data from a placebo-controlled 6-month clinical trial of once-daily atomoxetine. Results: The AISRS has high internal consistency, good convergent, and discriminant validities; modest divergent validity; and small ceiling and floor effects (≤1%). It correlates highly with the CAARS-Inv:SV. Factor analysis confirms 2 AISRS subscales, hyperactivity-impulsive scale and inattention. The AISRS total and AISRS subscales perform stably. All scales demonstrate responsiveness to change with medication. Conclusion: The AISRS and its subscales are robust, valid efficacy measures of ADHD symptoms in adult patients. Its anchored items and semistructured interview are advancements over existing scales. © 2010 SAGE Publications.

Eaton C.B.,Brown University | Hochberg M.C.,University of Maryland Baltimore County | Assaf A.,Pfizer | Cryer B.L.,University of Texas Southwestern Medical Center | And 8 more authors.
Seminars in Arthritis and Rheumatism | Year: 2011

Objectives: Gastrointestinal blood loss is a recognized complication of the use of nonsteroidal anti-inflammatory drugs (NSAIDS) in patients with arthritis. We examined the cross-sectional relationship of patient-reported outcomes of overall health, physical function, vitality, and quality of life to hemoglobin (hgb) levels in postmenopausal women with self-reported osteoarthritis to determine whether hgb levels as potential markers of chronic blood loss were associated with these functional outcomes. Methods: Postmenopausal women (N = 64,850) with self-reported osteoarthritis (srOA) at baseline in the Women's Health Initiative study, excluding participants with chronic or hemolytic diseases associated with anemia, had hgb levels measured and completed Short-Form Health Surveys. General linear models analysis adjusting for potential confounders was performed. Results: A nonlinear plateauing relationship between hgb levels and functional outcomes was found. Participants with srOA had statistically significantly worse overall health, physical function, and vitality, but not quality of life, for each gram of hgb below 14 g/dL, compared with those with hgb 14 g/dL (P < 0.001). Participants with srOA taking NSAIDS had worse functional outcomes for each level of hgb compared with those not reporting NSAIDS use. Conclusions: In cross-sectional analyses of postmenopausal women with srOA, differences in hgb levels are related to differences in functional outcomes of overall health, physical function, and vitality at clinically important levels. Prospective studies evaluating whether changes in hgb levels result in changes in functional outcomes in participants with osteoarthritis are needed to confirm of our findings and before any changes in therapeutics based on hemoglogin levels are considered in the care of patients with osteoarthritis. © 2011 Elsevier Inc.

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