Neural Correlates of Cognition Deficits in Mild Cognitive Impairment and Alzheimer's Disease

Oskar Dieter Peter Schönknecht^1,2, Pablo Toro², Aoife Hunt², Marcus Henze³, Uwe Haberkorn³, and Johannes Schröder²

Affiliations: ¹Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig; ²Section for Geriatric Psychiatry and ³German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit Nuclear Medicine and Department of Nuclear Medicine, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany

Correspondence: Dr Oskar Dieter Peter Schönknecht, Department of Psychiatry, University Hospital Leipzig, Semmelweisstr. 10,04103 Leipzig, Germany. Tel: +49-341-9724506; Fax: +49-341-9724569; e-mail: Peter.Schoenknecht@medizin.uni-leipzig.de

ABSTRACT

INTRODUCTION

Alzheimer's disease (AD) and mild cognitive impairment (MCI) as its preclinical syndrome are characterized by a variety of cognitive deficits that can be assessed by using the neuropsychological test battery of the CERAD. The cerebral changes underlying the respective cognitive deficits, however, are only partly understood.

METHODS

In 75 patients with mild AD and MCI, cerebral changes were investigated by positron emission tomography with Fluorodeoxyglucose. A regression analysis was performed in order to investigate the respective associations of regional cerebral glucose metabolism with the CERAD test scores by statistical parametric mapping.

RESULTS

Episodic memory scores were significantly correlated with glucose metabolism in temporo-frontal and cingulate cortices. Verbal fluency and naming scores were significantly correlated with glucose metabolism predominantly in left temporo-parietal and frontal cortices whereas constructional praxis test scores correlated significantly with left temporal and right frontal cortices. Both subtests of delayed episodic memory were associated with a network including rather frontal association cortices.

CONCLUSION

Findings of the study demonstrate that neuropsychological deficits as assessed by the CERAD refer to different cerebral sites of both hemispheres, and underline the clinical validity of this clinical instrument.

Substance Use Disorder in Adult Tourette Syndrome: Frequency, Profile, and Comorbidities

David G Lichter

Affiliation: Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

Correspondence: David G Lichter, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, 3495 Bailey Avenue, Buffalo, NY 14215, USA. Tel: +1-(716)-862-3141; Fax: +1-(716)-862-3140; e-mail: dlichter@buffalo.edu

ABSTRACT

INTRODUCTION

Previous studies have suggested that substance use disorder (SUD) may be over-represented in patients with Tourette syndrome (TS). Nevertheless, this association has received relatively little attention, despite the presence in both conditions of psychic urges or cravings and the prominence in TS of symptoms commonly associated with addiction, including mood and impulse-control dysregulation. The profile of SUD in TS is of both theoretical and practical interest, in view of the differential impact of certain common drugs of abuse on tics and other TS-related symptomatology.

OBJECTIVES

To assess the frequency, pattern, and comorbidities of SUD in a clinic population of adult TS subjects.

METHODS

Clinical records of adult TS patients followed at a University neurology clinic, which included formal ratings of tic and OCD severity, as well as information from a modified version of the Centre for Addiction and Mental Health Concurrent Disorders Screener (CAMH-CDS), were reviewed retrospectively. Patients with and without a history of SUD were compared with respect to severity of tics and comorbid psychiatric disorders.

RESULTS

Fifteen of the 66 TS patients (23%) had a history of SUD. Abused substances included not only those which might alleviate tics, such as cannabis and benzodiazepines, but also cocaine, with its strong tic-aggravating potential. Mood and impulse dysregulation in the form of panic disorder and rage attacks predicted SUD. Obsessive-compulsive disorder was not associated with SUD, consistent with the conceptual separation of both substance and behavioral addictions from obsessive-compulsive spectrum disorders.

CONCLUSIONS

SUD, primarily involving non-alcoholic substances, may be twice as common in symptomatic TS adults as in the general population, may be predicted by mood and impulse dysregulation and, in specific instances, may either drive or be driven by tics. These findings are considered in the context of dysfunction involving frontal-subcortical circuits and their modulating neurotransmitter systems, a pathobiology common to TS, SUD and linked psychiatric disorders. Management implications for TS patients at potential risk for SUD are discussed.

At a Loss for Words, and for a Single Letter: “D” Vitamin D, Dementia, and Depression in the Elderly

E Paul Cherniack

Affiliation: Department of Medicine, Division of Gerontology and Geriatric Medicine, Geriatrics Institute, University of Miami Miller School of Medicine, Bruce W. Carter Veterans Affairs Medical Center, Miami, FL, USA

Correspondence: E Paul Cherniack, Department of Medicine, Division of Gerontology and Geriatric Medicine, Geriatrics Institute, University of Miami Miller School of Medicine, Bruce W. Carter Veterans Affairs Medical Center Miami, FL, USA. Tel: +1-3055757101; e-mail: evan. cherniack@va.gov

ABSTRACT

An increasing number of investigations imply a relationship between lack of vitamin D and two common mental health problems in the elderly, dementia and depression. Vitamin D may have a protective effect on the brain against dementia through its beneficial effect on the systemic vasculature, including the cerebral vasculature, or it may protect or promote the growth of individual neurons. Several large epidemiologic trials and smaller studies have delineated an association between vitamin D and cognitive impairment in assessments using global screening tests and individual tests of specific cognitive function. Similarly, vitamin D levels have been correlated with the presence of depressive symptoms in older persons. A few small trials have used vitamin D to treat depression but have failed to use adequate doses. Larger randomized controlled trials are needed to assess the potential for vitamin D in the treatment of dementia and depression.

Affective Disorders, Mild Cognitive Impairment, and Risk for Dementia

Martine Simard

Affiliation: School of Psychology, Laval Uniuersity, Québec City, QC, Canada

Correspondence: Dr Martine Simard, Ecole de psychologie, Université Laval, Pavilion F.-A. Savard, Québec, G1V 0A6, QC, Canada. Tel: +1-(418)-656-2131, X12193; Fax: +1-(418)-656-3646; e-mail: martine.simard@psy.ulaval.ca

ABSTRACT

The concept of mild cognitive impairment (MCI) primarily emphasizes changes in individuals' cognitive functions, but it has recently been suggested that neuropsychiatric symptoms (NPS), and especially affective symptoms, should also be considered important factors in age-related neurodegeneration. This article reviews and summarizes recent evidence, published over the last 3 years, regarding the presence of various affective disorders in healthy older adults and MCI patients, and its relationship to risk for developing dementia. The results presented in this review show that depressive, apathetic, and anxious symptoms can be present in cognitively intact healthy elderly and MCI, and may predict progression to dementia. This article also provides suggestions for future research.

Anxiety and Cardiovascular Risk: Review of Epidemiological and Clinical Evidence

O Olafiranye¹, G Jean-Louis^1–3, F Zizi^1–3, J Nunes^3,4, and MT Vincent⁵

Affiliations: ¹Brooklyn Health Disparities Center, Department of Medicine, SUNY Downstate Medical Center, NY; ²Sleep Disorders Center, Department of Neurology, SUNY Downstate Medical Center, NY; ³Brooklyn Research Foundation on Minority Health, Kingdbrook Jewish Medical Center, NY; ⁴Sophie Davis School of Biomedical Education, City College New York, NY and ⁵Department of Family Medicine, SUNY Downstate Medical Center, NY, USA

Correspondence: Jean-Louis Girardin, Department of Medicine (Box 1199), SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203–2098, USA. Tel: (1)-718–270–2716; Fax: (1)-718–270–2917; e-mail: gjean-louis@downstate.edu

ABSTRACT

An increasing body of evidence suggests that anxiety is an independent predictor of adverse cardiovascular (CV) events. Individuals with high levels of anxiety are at increased risk of coronary heart disease, congestive heart failure, stroke, fatal ventricular arrhythmias, and sudden cardiac death. Anxiety following a major cardiac event can impede recovery, and is associated with a higher morbidity and mortality. This linkage between anxiety and CV disease is further corroborated by evidence suggesting that treatment of anxiety may improve cardiac symptoms. However, the mechanisms underlying the observed associations are not entirely delineated. Several intermediary mechanisms have been suggested, including sympathetic activation, impaired vagal control, reduced heart rate variability, stimulation of the hypothalamic–pituitary axis, hyperventilation-induced coronary spasm, oxidative stress, increased inflammatory mediators, and unhealthy lifestyle. There is a need for several clinical trials to explicate the complex associations between anxiety and CV disease, which may be compounded by the involvement of other psychosocial factors. In this review, we examine the epidemiological evidence for the association between anxiety and CV disease, and discuss the proposed mechanisms that may be responsible for this association.

A Review of Psychotherapy for Obsessive-Compulsive Disorder

Lindsay Brauer¹, Adam B Lewin² and Eric A Storch²

Affiliations: ¹Department of Psychology, University of South Florida, Tampa, Florida, USA and ²Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida, St. Petersburg, Florida, USA

Correspondence: Eric A Storch, All Children’s Hospital guild Endowed Chair, Departments of Pediatrics and Psychiatry, Rothman Center for Neuropsychiatry, University of South Florida, 880 6th Street South, 4th Floor North, Box 7523, St. Petersburg, FL 33701, USA. Tel: +1 727 767 8230. Fax: +1 727 767 7786; e-mail: estorch@health.usf.edu

ABSTRACT

Cognitive-behavioral therapy (CBT) is a first-line treatment for obsessive-compulsive disorder (OCD) in adults and children due to its efficacy, maintenance of therapeutic gains after treatment withdrawal, safety, and tolerability. The current article reviews research regarding the theoretical underpinnings of CBT, pragmatics regarding CBT implementation, and efficacy findings, while also highlighting barriers to efficacious treatment (ie, age, comorbidity, geography), methods of addressing such issues, and areas in need of further study.

Psychopharmacological Treatments for Emotion Dysregulation in Borderline Personality Disorder

Elena I Nica¹ and Paul S Links²

Affiliations: ¹Faculty of Medicine, University of Toronto, Ontario, Canada and ²Arthur Sommer Rotenberg Chair in Suicide Studies and Professor of Psychiatry in the Department of Psychiatry, Faculty of Medicine, St. Michael's HospitalUniversity of Toronto, and the Centre for Research in Inner City Health in The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada

Correspondence: Elena I. Nica, Faculty of Medicine, University of Toronto, St. Michael's Hospital, 30 Bond Street, Shutter Wing, Room 2010d, Toronto, Ontario M5B1W8, Canada. Tel: +416 997 1605; Fax: +1 416 864 5996; e-mail: irina.nica@utoronto.ca

ABSTRACT

The drug treatment of affective symptoms in borderline personality disorder (BPD) has been the subject of four recent meta-analyses of randomized controlled studies (RCTs). This paper reviews the current evidence-based recommendations for the psychopharmacological treatment of the affective symptoms in BPD: affective instability, anger, depression, and anxiety. There was not enough data on affective instability as an outcome measure to make a good conclusion. Most of the evidence point to a large reduction of anger with mood stabilizers and antipsychotics. Mood stabilizers are also moderately effective against depressed mood and anxiety. Contrary to prior guidelines, selective serotonin reuptake inhibitors (SSRIs) were shown to be minimally effective against depression in BPD. Omega 3 fatty acids helped reduce depression. These results suggest that clinicians should raise their threshold for prescribing medication for affective instability, anxiety, and depression, but not for anger. Clinicians must also weigh the benefits of medication over their side effects in the neurologic and metabolic domains. The meta-analyses were limited by the heterogeneity in methodology, by the small number of RCTs for each drug and small sample sizes, and by the exclusion of patients with comorbidities that are common in this population.

Interaction of Genes and Environment in Adolescent Substance Use: Opportunities and Implications for Interventions

Richard Rende

Affiliation: Transdisciplinary Research Group, Department of Psychiatry and Human Behavior, Alpert Medical School, Butler Hospital, Brown University, Providence, Rhode Island

Correspondence: Richard Rende, Transdisciplinary Research Group, Department of Psychiatry and Human Behavior, Alpert Medical School, Butler Hospital, 345 Blackstone Blvd., Providence 02906, Rhode Island. Tel: (401) 455-2481; Fax: (401) 455-6611; e-mail: r.rende@comcast.net

ABSTRACT

It is well recognized that adolescence is now a period of development in which the roots of substance abuse and dependence are put down. As such, there is an appreciation of the importance of delivering psychosocial interventions that could curtail adolescent use and prevent escalation into problematic levels of use. This paper reviews the rationale of psychosocial interventions from the perspective of genetic epidemiology. Genetically informative studies are discussed as laying a foundation that emphasizes the importance of shared environmental influences as targets for psychosocial interventions that could reduce early levels of substance use in adolescence, and serve as a blockade for the activation of genes that underlie progression to heavier use, as well as abuse and dependence. Recent conceptual and empirical approaches to gene-environment interplay are discussed with reference to the specific case of delivering psychosocial interventions. The implications for merging the intervention mindset with the tools of genetic epidemiology are discussed.

The Appalachian Tri-State Node Experiences with the National Institute on Drug Abuse Clinical Trials Network

Thomas M Kelly, Dennis C Daley, Mimmie Byrne, Larry DeMarzo, Doris Smith and Stephanie Madl

Affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania

Correspondence: Thomas M. Kelly, Associate Professor of Psychiatry, University of Pittsburgh, School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara St., Pittsburgh, PA 15213. Tel: 412 246 5152; Fax: 412 246 6047; e-mail: kellytm@upmc.edu

ABSTRACT

The National Institute on Drug Abuse (NIDA)-sponsored Clinical Trial Network (CTN) recently celebrated 10 years of conducting “real world” research into the treatment of addiction. This article reviews the history and results of the most recent CTN studies and describes the experiences of one of the 13 participating research affiliates, the Appalachian Tri-State (ATS) Node. We discuss our “bidirectional” collaboration with multiple community treatment programs (CTPs) on research and dissemination activities and include their experiences as a member of our ATS Node.

Results of CTN clinical trials have found unexpectedly that treatment as usual (TAU) is often almost as good as evidence-based interventions such as Motivational Interviewing (MI), possibly due to the difficulty in implementing evidence-based practices most effectively among divergent treatment sites and heterogeneous clinical populations. Some expected findings from the reviewed research are that severity of addiction and comorbidity moderate treatment outcomes and must be accounted for in future CTN-sponsored studies. Notwithstanding these results, much has been learned and recommendations are suggested for changes in CTN research designs that will address methodological limitations and increase treatment effectiveness in future CTN studies.

Cotard's Syndrome

Hans Debruyne^1,2,3, Michael Portzky¹, Kathelijne Peremans¹ and Kurt Audenaert¹

Affiliations: ¹Department of Psychiatry, University Hospital Ghent, Ghent, Belgium; ²PC Dr. Guislain, Psychiatric Hospital, Ghent, Belgium and ³Department of Psychiatry, Zorgsaam/RGC, Terneuzen, The Netherlands

Correspondence: Hans Debruyne, P.C. Dr. Guislain Psychiatric Hospital Ghent, Fr. Ferrerlaan 88A, 9000 Ghent, Belgium. Tel: +32 9 216 3311; Fax: +32 9 2163312; e-mail: hans.debruyne@fracarita.org

ABSTRACT

Cotard's syndrome is characterized by nihilistic delusions focused on the individual's body including loss of body parts, being dead, or not existing at all. The syndrome as such is neither mentioned in DSM-IV-TR nor in ICD-10. There is growing unanimity that Cotard's syndrome with its typical nihilistic delusions externalizes an underlying disorder. Despite the fact that Cotard's syndrome is not a diagnostic entity in our current classification systems, recognition of the syndrome and a specific approach toward the patient is mandatory.

This paper overviews the historical aspects, clinical characteristics, classification, epidemiology, and etiological issues and includes recent views on pathogenesis and neuroimaging. A short overview of treatment options will be discussed.

ADHD, Brain Functioning, and Transcendental Meditation Practice

Frederick Travis^1,2, Sarina Grosswald² and William Stixrud³

Affiliations: ¹Director, Center for the Brain, Consciousness, and Cognition, 1000 North 4th Street, Fairfield, IA 52557, USA; ²Maharishi University of Management Research Institute, Maharishi Vedic City, IA 52557, USA and ³Department of Psychiatry, George Washington University School of Medicine and Health Sciences, Washington, DC 20057, USA

Correspondence: Frederick Travis, PhD, Director, Center for the Brain, Consciousness, and Cognition, 1000 North 4th Street, Fairfield, IA 52557, USA. Tel/Fax: 641 472 1209; e-mail: ftravis@mum.edu

ABSTRACT

This random-assignment pilot study investigated effects of Transcendental Meditation (TM) practice on task performance and brain functioning in 18 ADHD students, age 11–14 years. Students were pretested, randomly assigned to TM or delayed-start comparison groups, and posttested at 3- and 6-months. Delayed-start students learned TM after the 3-month posttest. Three months TM practice resulted in significant decreases in theta/beta ratios, increased theta coherence, a trend for increased alpha and beta1 coherence, and increased Letter Fluency. The delayed-start group similarly had decreased theta/beta ratios and increased letter fluency at the 6-month posttest, after they practiced TM for 3 months. Also, all students significantly improved on five ADHD-symptoms over the six months of the study, as reported in the parent's survey. These findings warrant additional research to assess the impact of TM practice as a nondrug treatment of ADHD.