Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury.

Brain Inj. 2010 Nov 30;

Authors: Reimunde P, Quintana A, Castañón B, Casteleiro N, Vilarnovo Z, Otero A, Devesa A, Otero-Cepeda XL, Devesa J

Objective: To assess the effects of growth hormone (GH) treatment combined with cognitive rehabilitation in patients with adult growth hormone deficiency (GHD) and cognitive disorders occurring after traumatic brain injury (TBI). Participants: Nineteen adult patients with TBI: GHD was found in 11 of them. Intervention: Patients were treated with GH (GHD; sc; 1 mg/day) or vehicle (controls; sc; 1 mg/day); daily cognitive rehabilitation therapy was performed in both groups for 3 months. Main outcome measures: The GHRH-arginine test established GHD. The neuropsychological test WAIS was performed before commencing the treatment and 3 months after commencing it. Results: Controls achieved significant improvements in digits and in manipulative intelligence quotient (IQ) (p < 0.05 vs. baseline). GHD achieved significant improvements in more cognitive parameters: understanding, digits, numbers and incomplete figures (p < 0.05 vs. baseline) and similarities, vocabulary, verbal IQ, manipulative IQ and total IQ (p < 0.01). GHD reached significantly greater improvements than controls in similarities (p < 0.01) and in vocabulary, verbal IQ and total IQ (p < 0.05). Conclusion: GH administration significantly improved cognitive rehabilitation in GHD patients. Since at the end of treatment period plasma IGF-I levels were similar in both groups it is likely that exogenous GH administration is responsible for the significant differences found.

PMID: 21117918 [PubMed - as supplied by publisher]

Dan Gardner, MD

Phone/fax: 858-560-5609

www.danielgardner.yourmd.com

Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury.

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Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury.

Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury.

Brain Inj. 2010 Nov 30;

Authors: Reimunde P, Quintana A, Castañón B, Casteleiro N, Vilarnovo Z, Otero A, Devesa A, Otero-Cepeda XL, Devesa J

Objective: To assess the effects of growth hormone (GH) treatment combined with cognitive rehabilitation in patients with adult growth hormone deficiency (GHD) and cognitive disorders occurring after traumatic brain injury (TBI). Participants: Nineteen adult patients with TBI: GHD was found in 11 of them. Intervention: Patients were treated with GH (GHD; sc; 1 mg/day) or vehicle (controls; sc; 1 mg/day); daily cognitive rehabilitation therapy was performed in both groups for 3 months. Main outcome measures: The GHRH-arginine test established GHD. The neuropsychological test WAIS was performed before commencing the treatment and 3 months after commencing it. Results: Controls achieved significant improvements in digits and in manipulative intelligence quotient (IQ) (p < 0.05 vs. baseline). GHD achieved significant improvements in more cognitive parameters: understanding, digits, numbers and incomplete figures (p < 0.05 vs. baseline) and similarities, vocabulary, verbal IQ, manipulative IQ and total IQ (p < 0.01). GHD reached significantly greater improvements than controls in similarities (p < 0.01) and in vocabulary, verbal IQ and total IQ (p < 0.05). Conclusion: GH administration significantly improved cognitive rehabilitation in GHD patients. Since at the end of treatment period plasma IGF-I levels were similar in both groups it is likely that exogenous GH administration is responsible for the significant differences found.

PMID: 21117918 [PubMed - as supplied by publisher]

Dan Gardner, MD

Phone/fax: 858-560-5609

www.danielgardner.yourmd.com

Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered.

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Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered.

Hum Psychopharmacol. 2010 Apr;25(3):193-200

Authors: Hindmarch I, Hashimoto K

Cognitive impairment is a primary feature of patients with major depressive disorder (MDD) and is characterised by stress-induced neural atrophy. Via alpha-adrenergic, anti-cholinergic and anti-histaminic activities, several antidepressants can cause significant counter-therapeutic cognitive impairment. Evidence is emerging of the involvement of sigma-1 receptor agonism in the mechanism of action of some antidepressants, notably fluvoxamine. Sigma-1 receptors are abundant in areas affected by depression/stress-induced cerebral atrophy and their ligands have a unique pharmacological profile; they may promote neurogenesis and initiate adaptive neural plasticity as a protection/reaction to stress. Fluvoxamine, as a potent sigma-1 receptor agonist, has shown ameliorating effects in animal models of psychosis, depression, stress, anxiety, obsessive-compulsive disorder (OCD) and aggression and has been shown to improve cognitive impairments. In humans, fluvoxamine may repair central nervous system (CNS) atrophy and restore cognitive function. The current review explores the mechanisms through which sigma-1 receptors can modulate cognitive function and examines how antidepressant therapy with fluvoxamine may help improve cognitive outcomes in patients with depression.

PMID: 20373470 [PubMed - indexed for MEDLINE]

Effectiveness of Japanese herbal medicine yokukansan for alleviating psychiatric symptoms after traumatic brain injury.

Psychogeriatrics. 2010 Mar;10(1):45-8.

Saito S, Kobayashi T, Osawa T, Kato S.

Department of Psychiatry, Jichi Medical University, Shimotsuke City, Tochigi, Japan. saitoshinnosuke@gmail.com

Abstract

The Japanese herbal medicine, yokukansan, has been reported to improve behavioral and psychological symptoms of dementia and activities of daily living in patients with dementia. In the present case report, the authors report the effectiveness of yokukansan in treating psychiatric symptoms after traumatic brain injury. An 85-year-old man, who underwent surgery for hepatic portal cholangiocarcinoma, sustained traumatic brain injury after falling from bed as the result of postoperative delirium. He subsequently presented with psychiatric symptoms, showing markedly impulsive and aggressive behavior. Neuroleptics did not alleviate the symptoms. Ultimately, we succeeded in controlling the symptoms, without adverse effects, by giving the patient yokukansan. Yokukansan shows the potential for reducing aggressive and impulsive behavior in dementia as well as in other psychiatric diseases.

PMID: 20594286 [PubMed - indexed for MEDLINE]

Limbic Metabolic Abnormalities in Remote Traumatic Brain Injury and Correlation With Psychiatric Morbidity and Social Functioning

Limbic Metabolic Abnormalities in Remote Traumatic Brain Injury and Correlation With Psychiatric Morbidity and Social Functioning

Neuropsychiatry Clin Neurosci 22:370-377, Fall
doi: 10.1176/appi.neuropsych.22.4.370
© 2010 American Neuropsychiatric Association
Arístides A. Capizzano, M.D., Ricardo E. Jorge, M.D. and Robert G. Robinson, M.D.

Received August 5, 2009; revised October 21 and November 13, 2009; accepted November 16, 2009. Dr. Capizzano is affiliated with the Department of Radiology, Division of Neuroradiology, at the University of Iowa Carver College of Medicine in Iowa City, Iowa; Drs. Jorge and Robinson are affiliated with the Department of Psychiatry at the University of Iowa Carver College of Medicine in Iowa City. Address correspondence to Aristides A. Capizzano, M.D., Department of Radiology, Division of Neuroradiology, University of Iowa Carver College of Medicine, 200 Hawkins Dr., Iowa City, IA 52242; aristides-capizzano@uiowa.edu (e-mail).

The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (r_s=–0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status.

Transcranial Magnetic Stimulation for Depression After a Traumatic Brain Injury: A Case Study.

Related Articles

Transcranial Magnetic Stimulation for Depression After a Traumatic Brain Injury: A Case Study.

J ECT. 2010 Oct 5;

Authors: Fitzgerald PB, Hoy KE, Maller JJ, Herring S, Segrave R, McQueen S, Peachey A, Hollander Y, Anderson JF, Daskalakis ZJ

Depression after a traumatic brain injury (TBI) is very common, yet there is a lack of evidence-based treatment options for people who experience depression after a TBI. Traditionally, a history of TBI has been considered an exclusion criterion for transcranial magnetic stimulation trials because of the increased risk of seizure after a TBI. We present what we believe to be the first case of a patient with depression after a TBI treated with transcranial magnetic stimulation.

PMID: 20938348 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20938348&dopt=Abstract

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Dan Gardner, M.D.

www.danielgardner.yourmd.com

dgardner@ucsd.edu  858-560-5609

Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer's dis

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Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer's disease in an open-label pilot study.

Am J Alzheimers Dis Other Demen. 2010 Jun;25(4):367-71

Authors: Remington R, Chan A, Lepore A, Kotlya E, Shea TB

Preclinical studies demonstrate that apple juice exerts multiple beneficial effects including reduction of central nervous system oxidative damage, suppression of Alzheimer's disease (AD) hallmarks, improved cognitive performance, and organized synaptic signaling. Herein, we initiated an open-label clinical trial in which 21 institutionalized individuals with moderate-to-severe AD consumed 2 4-oz glasses of apple juice daily for 1 month. Participants demonstrated no change in the Dementia Rating Scale, and institutional caregivers reported no change in Alzheimer's Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) in this brief study. However, caregivers reported an approximate 27% (P < .01) improvement in behavioral and psychotic symptoms associated with dementia as quantified by the Neuropsychiatric Inventory, with the largest changes in anxiety, agitation, and delusion. This pilot study suggests that apple juice may be a useful supplement, perhaps to augment pharmacological approaches, for attenuating the decline in mood that accompanies progression of AD, which may also reduce caregiver burden.

PMID: 20338990 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20338990&dopt=Abstract

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Dan Gardner, M.D.

www.danielgardner.yourmd.com

dgardner@ucsd.edu  858-560-5609

Texture analysis of MR images of patients with mild traumatic brain injury.

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Texture analysis of MR images of patients with mild traumatic brain injury.

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Texture analysis of MR images of patients with mild traumatic brain injury.

BMC Med Imaging. 2010;10:8

Authors: Holli KK, Harrison L, Dastidar P, Wäljas M, Liimatainen S, Luukkaala T, Ohman J, Soimakallio S, Eskola H

BACKGROUND: Our objective was to study the effect of trauma on texture features in cerebral tissue in mild traumatic brain injury (MTBI). Our hypothesis was that a mild trauma may cause microstructural changes, which are not necessarily perceptible by visual inspection but could be detected with texture analysis (TA). METHODS: We imaged 42 MTBI patients by using 1.5 T MRI within three weeks of onset of trauma. TA was performed on the area of mesencephalon, cerebral white matter at the levels of mesencephalon, corona radiata and centrum semiovale and in different segments of corpus callosum (CC) which have been found to be sensitive to damage. The same procedure was carried out on a control group of ten healthy volunteers. Patients' TA data was compared with the TA results of the control group comparing the amount of statistically significantly differing TA parameters between the left and right sides of the cerebral tissue and comparing the most discriminative parameters. RESULTS: There were statistically significant differences especially in several co-occurrence and run-length matrix based parameters between left and right side in the area of mesencephalon, in cerebral white matter at the level of corona radiata and in the segments of CC in patients. Considerably less difference was observed in the healthy controls. CONCLUSIONS: TA revealed significant changes in texture parameters of cerebral tissue between hemispheres and CC segments in TBI patients. TA may serve as a novel additional tool for detecting the conventionally invisible changes in cerebral tissue in MTBI and help the clinicians to make an early diagnosis.

PMID: 20462439 [PubMed - indexed for MEDLINE]

Dan Gardner, MD

Phone/fax: 858-560-5609

www.danielgardner.yourmd.com

Texture analysis of MR images of patients with mild traumatic brain injury.

Texture analysis of MR images of patients with mild traumatic brain injury.

Related Articles

Texture analysis of MR images of patients with mild traumatic brain injury.

BMC Med Imaging. 2010;10:8

Authors: Holli KK, Harrison L, Dastidar P, Wäljas M, Liimatainen S, Luukkaala T, Ohman J, Soimakallio S, Eskola H

BACKGROUND: Our objective was to study the effect of trauma on texture features in cerebral tissue in mild traumatic brain injury (MTBI). Our hypothesis was that a mild trauma may cause microstructural changes, which are not necessarily perceptible by visual inspection but could be detected with texture analysis (TA). METHODS: We imaged 42 MTBI patients by using 1.5 T MRI within three weeks of onset of trauma. TA was performed on the area of mesencephalon, cerebral white matter at the levels of mesencephalon, corona radiata and centrum semiovale and in different segments of corpus callosum (CC) which have been found to be sensitive to damage. The same procedure was carried out on a control group of ten healthy volunteers. Patients' TA data was compared with the TA results of the control group comparing the amount of statistically significantly differing TA parameters between the left and right sides of the cerebral tissue and comparing the most discriminative parameters. RESULTS: There were statistically significant differences especially in several co-occurrence and run-length matrix based parameters between left and right side in the area of mesencephalon, in cerebral white matter at the level of corona radiata and in the segments of CC in patients. Considerably less difference was observed in the healthy controls. CONCLUSIONS: TA revealed significant changes in texture parameters of cerebral tissue between hemispheres and CC segments in TBI patients. TA may serve as a novel additional tool for detecting the conventionally invisible changes in cerebral tissue in MTBI and help the clinicians to make an early diagnosis.

PMID: 20462439 [PubMed - indexed for MEDLINE]

Dan Gardner, MD

Phone/fax: 858-560-5609

www.danielgardner.yourmd.com

H3 Receptor Miniseries: Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease

1. Jorge D. Brioni*,
2. Tim Esbenshade,
3. Tiffany Garrison,
4. Scott Bitner and
5. Marlon Cowart

+ Author Affiliations

1.      Abbott Laboratories

1. * Corresponding author; email: jorge.brioni@abbott.com

Abstract

H3 antagonists increase the release of brain histamine, ACh, NE and DA, neurotransmitters that are known to modulate cognitive processes. The ability to release brain histamine support the effect on attention and vigilance, but histamine also modulates other cognitive domains like short-term and long-term memory. A number of H3 antagonists including BF2.649, PF-03654746, GSK189254, MK-0249, JNJ-17216498 and ABT-288 have advanced to the clinical area for the potential treatment of human cognitive disorders. H3 antagonists exhibited wake promoting effects in humans and efficacy in narcoleptic patients indicating target engagement but some of them were not efficacious in ADHD and schizophrenic patients. Preclinical studies have also shown that H3 antagonists activate intracellular signaling pathways that may improve cognitive efficacy as well as disease modifying effects in Alzheimer's. Ongoing clinical studies will be able to determine the utility of H3 antagonists for the treatment of cognitive disorders in humans.

Vitamins B12, B6, and folic acid for cognition in older men

Vitamins B12, B6, and folic acid for cognition in older men -- Ford et al., 10.1212/WNL.0b013e3181f962c4 -- Neurology

Received April 5, 2010
Accepted June 17, 2010
A. H. Ford MD^*, L. Flicker MD, H. Alfonso PhD, J. Thomas RN, R. Clarnette MD, R. Martins PhD, and O. P. Almeida MD

From the Centre for Medical Research & School of Psychiatry and Clinical Neurosciences (A.H.F., H.A., R.M., O.P.A.) and the Centre for Medical Research & School of Medicine and Pharmacology (L.F., J.T.), WA Centre for Health & Ageing, University of Western Australia, Perth, WA; and the WA Centre for Alzheimer's Disease Research and Care (R.C., R.M.), Edith Cowan University, Perth, WA, Australia.

^* To whom correspondence should be addressed. E-mail: andrew.ford@uwa.edu.au.

Objective: To investigate whether supplementing older men with vitamins B₁₂, B₆, and folic acid improves cognitive function.

Methods: The investigators recruited 299 community-representative hypertensive men 75 years and older to a randomized, double-blind controlled clinical trial of folic acid, vitamin B₆, and B₁₂ supplementation vs placebo over 2 years. The primary outcome of interest was the change in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog). A secondary aim of the study was to determine if supplementation with vitamins decreased the risk of cognitive impairment and dementia over 8 years.

Results: The groups were well-balanced for demographic and biochemical parameters. There was no difference in the ADAS-cog change from baseline to 24 months between the placebo (0.8, SD 4.0) and vitamins group (0.7, SD 3.4). The adjusted scores in the treatment groups did not differ over time (placebo 0.2 lower, z = 0.71, p = 0.478). There was a nonsignificant 28% decrease in the risk of cognitive impairment (odds ratio 0.72, 95% confidence interval 0.25–2.09) and dementia (hazard ratio 0.72, 95% confidence interval 0.29–1.78) over 8 years of follow-up.

Conclusions: The daily supplementation of vitamins B₁₂, B₆, and folic acid does not benefit cognitive function in older men, nor does it reduce the risk of cognitive impairment or dementia.

Classification of evidence: This study provides Class I evidence that vitamin supplementation with daily doses of 400 μg of B₁₂, 2 mg of folic acid, and 25 mg of B₆ over 2 years does not improve cognitive function in hypertensive men aged 75 and older.

Screening for mild traumatic brain injury in the presence of psychiatric comorbiditie

	Arch Phys Med Rehabil. 2010 Jul;91(7):1082-6. Screening for mild traumatic brain injury in the presence of psychiatric comorbidities. Chapman JC, Andersen AM, Roselli LA, Meyers NM, Pincus JH. War Related Illness and Injury Study Center, Veterans Affairs Medical Center, Washington, DC, USA. Julie.Chapman@va.gov Abstract OBJECTIVE: To determine whether or not a battery of neurobehavioral tests, the Brief Objective Neurobehavioral Detector (BOND), could detect mild traumatic brain injury (mTBI) among a group of psychiatric inpatients with numerous substance-related and medical comorbidities. The 16-item BOND is comprised of neurologic examination tasks and has been shown to correlate with radiologic and cognitive findings in previous studies. DESIGN: Masked comparison. SETTING: Inpatient psychiatric unit at the Veterans Affairs Medical Center in Washington, DC. PARTICIPANTS: Patients (N=51) sequentially admitted for suicidal ideation in the context of various psychiatric disorders. INTERVENTIONS: No intervention. MAIN OUTCOME MEASURE: BOND total and subtest scores. RESULTS: Forty-three patients were eligible and analyzed. Twenty-seven had sustained an mTBI in the distant past, and 16 had never sustained a traumatic brain injury (TBI) (non-TBI group). On average, the mTBI group demonstrated a significantly greater number of abnormal subtests on the BOND (mean, 7.22) than did the non-TBI group (mean, 4.50; P=.003). Although the BOND significantly correlated with the presence of mTBI, it did not correlate with any of the psychiatric, substance-related, or medical comorbidities. Multiple regressions indicated that the BOND total score was not explained by age, posttraumatic stress disorder diagnosis, or any combination of the psychiatric, substance-related, or medical comorbidities. High rates of sensitivity (70%) and specificity (69%) were found. CONCLUSIONS: The results of this pilot study suggest that the inexpensive, brief, and objective BOND instrument may be a useful screening tool for the detection of subtle neurologic brain abnormalities after mTBI, even in the presence of substantial comorbidities.
	PMID: 20599047 [PubMed - indexed for MEDLINE]

Memantine versus donepezil in mild to moderate Alzheimer's disease: a random...

Memantine versus donepezil in mild to moderate Alzheimer's disease: a randomized trial with magnetic resonance spectroscopy.

via pubmed: "alzheimer's disease... by Modrego PJ, Fayed N, Errea JM, Rios C, Pina MA, Sarasa M on 8/26/10

Related Articles

Memantine versus donepezil in mild to moderate Alzheimer's disease: a randomized trial with magnetic resonance spectroscopy.

Eur J Neurol. 2010 Mar;17(3):405-12

Authors: Modrego PJ, Fayed N, Errea JM, Rios C, Pina MA, Sarasa M

BACKGROUND AND PURPOSE: To compare memantine with the most prescribed cholinesterase inhibitor (donepezil) from a clinical viewpoint when administered in early phases of Alzheimer disease (AD), and to find out whether memantine may produce changes in brain metabolite concentrations in comparison with donepezil. METHODS: In this comparative rater-blinded parallel group randomized trial we recruited a consecutive sample of patients with probable mild to moderate AD. At baseline we carried out neuropsychological assessment with mini-mental, Clinical Dementia Rating Scale (CDR), Blessed Dementia Rating Scale, Alzheimer's Disease Assessment Scale, cognitive part (ADAS-cog), neuropsychiatric inventory (NPI), and disability assessment for dementia (DAD), as well as (1)H magnetic resonance spectroscopy (MRS) in several areas of the brain. Patients were randomized to receive either donepezil or memantine for 6 months. After this elapse of time we repeated the same procedures and observed the changes in clinical scales (ADAS-cog, NPI, DAD), as well as the changes in metabolite levels in every area of exploration (temporal, pre-frontal, posterior cingulated (PCG), and occipital), especially those of N-acetyl-aspartate (NAA) which is regarded as a surrogate marker of neuronal density. RESULTS: A total of sixty-three patients completed the trial. We did not see significant differences in clinical scales and metabolite levels between those on donepezil (n = 32) and those on memantine (n = 31). In general, more patients worsened than improved on either of the drugs. The changes in the NAA/creatine ratio in the PCG correlated significantly with the changes in the ADAS-cog (P = 0.004). CONCLUSIONS: Donepezil and memantine have similar modest clinical and spectroscopic effect on mild to moderate AD. MRS could be useful to monitor progression of the disease.

PMID: 19874395 [PubMed - indexed for MEDLINE]

Statins for the treatment of dementia.

Statins for the treatment of dementia.

via pubmed: "alzheimer's disease... by McGuinness B, O'Hare J, Craig D, Bullock R, Malouf R, Passmore P on 8/26/10

Related Articles

Statins for the treatment of dementia.

Cochrane Database Syst Rev. 2010;8:CD007514

Authors: McGuinness B, O'Hare J, Craig D, Bullock R, Malouf R, Passmore P

BACKGROUND: The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD ss-amyloid protein (Ass) is deposited in the form of extracellular plaques and previous studies have determined Ass generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction it is biologically plausible they may be efficacious in the treatment of AD and dementia. OBJECTIVES: To assess the clinical efficacy and tolerability of statins in the treatment of dementia. SEARCH STRATEGY: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (27 October 2008). SELECTION CRITERIA: Double-blind, randomized controlled trials of statins given for at least six months in people with a diagnosis of dementia. DATA COLLECTION AND ANALYSIS: Two independent authors extracted and assessed data independently against the inclusion criteria. Data were pooled where appropriate and entered into a meta-analysis. MAIN RESULTS: Three studies were identified (748 participants, age range 50-90 years). All patients had a diagnosis of probable or possible AD according to standard criteria and most patients were established on a cholinesterase inhibitor. Treatment in ADCLT 2005 consisted of 80mg atorvastatin compared to placebo for 52 weeks, serum low density lipoprotein (LDL) cholesterol was reduced by 54% in the atorvastatin group. Treatment in Simons 2002 consisted of 40mg simvastatin compared to placebo for 26 weeks, serum LDL cholesterol was reduced by 52% in the simvastatin group. Treatment in LEADe 2010 consisted of 80mg atorvastatin compared to placebo for 72 weeks, LDL cholesterol was reduced by 50.2% by month 3 and remained constant through month 18. Change in Alzheimer's Disease Assessment Scale- cognitive subscale (ADAS-Cog) from baseline was a primary outcome in 3 studies; when data were pooled there was considerable heterogeneity so the random effects model was used, statins did not provide any beneficial effect in this cognitive measure [mean difference -1.12, 95% CI -3.99, 1.75, p = 0.44]. All studies provided change in Mini Mental State Examination (MMSE) from baseline; again random effects model was used due to considerable heterogeneity: there was no significant benefit from statins in this cognitive measure when the data were pooled [mean difference -1.53, 95% CI -3.28, 0.21, p = 0.08]. There was some evidence that patients on statins in ADCLT 2005 maintained better cognitive function if serum cholesterol was high at baseline, MMSE was higher at baseline or if they had an apolipoprotein E4 allele present. This would need to be confirmed in larger studies however. Treatment related adverse effects were available from two studies, LEADe 2010 and Simons 2002; when data were pooled there was no significant difference between statins and placebo [odds ratio 2.45, 95% CI 0.69, 8.62, p = 0.16]. There was no significant difference in global function, behaviour or activities of daily living in the statin and placebo groups. One large randomised controlled trial (RCT) ( CLASP 2008) has not yet published its results. There were no studies identified assessing role of statins in treatment of VaD. There was no evidence that statins were detrimental to cognition. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend statins for the treatment of dementia. Analysis from the studies available, including one large RCT, indicate statins have no benefit on the outcome measures ADAS-Cog or MMSE. We need to await full results from CLASP 2008 before we can be certain. This Cochrane review will be updated as these results become available.

PMID: 20687089 [PubMed - indexed for MEDLINE]

Group interactive structured treatment (GIST): A social competence intervent...

Group interactive structured treatment (GIST): A social competence intervention for individuals with brain injury.

via pubmed: "traumatic brain inj... by Hawley LA, Newman JK on 8/26/10

Group interactive structured treatment (GIST): A social competence intervention for individuals with brain injury.

Brain Inj. 2010 Aug 25;

Authors: Hawley LA, Newman JK

Background: Impairments in social competence are among the most prevalent sequelae of traumatic brain injury and present a major barrier to a person returning to a productive life. The recent increased incidence of TBI among military personnel and the subsequent difficulties these individuals face reintegrating into society accentuates the need for efficacious social competence treatment interventions for the TBI population. Method and results: This paper outlines the theoretical model and clinical application of Group Interactive Structured Treatment (GIST) for Social Competence. GIST- Social Competence is a structured cognitive-behavioural group therapy model addressing the underlying cognitive, communicative and emotional impairments impeding social competence after TBI. A recent randomized control trial (RCT) funded by the National Institute on Disability and Rehabilitation Research demonstrated the efficacy of this programme. GIST integrates the principles of established cognitive-behavioural therapy, group therapy and holistic neuro-rehabilitation in a manualized 13 week intervention combining a structured curriculum with a group therapy format. The structured cognitive-behavioural approach allows even those with significant underlying deficits (including self-awareness, memory, problem-solving, etc.) to benefit from this intervention. Conclusion: The GIST model can be applied to other treatment areas in TBI rehabilitation. Clinical observations from application of GIST with military personnel are reviewed.

PMID: 20735320 [PubMed - as supplied by publisher]

(1)H-MR Spectroscopy in Traumatic Brain Injury.

(1)H-MR Spectroscopy in Traumatic Brain Injury.

via pubmed: (tbi imaging) and (s... by Marino S, Ciurleo R, Bramanti P, Federico A, De Stefano N on 8/26/10

(1)H-MR Spectroscopy in Traumatic Brain Injury.

Neurocrit Care. 2010 Aug 25;

Authors: Marino S, Ciurleo R, Bramanti P, Federico A, De Stefano N

Traumatic brain injury (TBI) is a common cause of neurological damage and disability. Conventional imaging (CT scan or MRI) is highly sensitive in detecting lesions and provides important clinical information regarding the need for acute intervention. However, abnormalities detected by CT scan or conventional MRI have limited importance in the classification of the degree of clinical severity and in predicting patients' outcome. This can be explained by the widespread microscopic tissue damage occurring after trauma, which is not observable with the conventional structural imaging methods. Advances in neuroimaging over the past two decades have greatly helped in the clinical care and management of patients with TBI. The advent of newer and more sensitive imaging techniques is now being used to better characterize the nature and evolution of injury and the underlying mechanisms that lead to progressive neurodegeneration, recovery or subsequent plasticity. This review will describe the role of proton magnetic resonance spectroscopic (MRS), an advanced MRI technique as related to its use in TBI. Proton MRS is a noninvasive approach that acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and allows to assess clinical severity and to predict disease outcome.

PMID: 20737247 [PubMed - as supplied by publisher]

Agomelatine, the first melatonergic antidepressant

Agomelatine, the first melatonergic antidepressant: discovery, characterization and development.

via pubmed: "depression/therapy"... by de Bodinat C, Guardiola-Lemaitre B, Mocaër E, Renard P, Muñoz C, Millan MJ on 8/26/10

www.nature.com-images-logo_nrdd.gif" border="0" />

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Agomelatine, the first melatonergic antidepressant: discovery, characterization and development.

Nat Rev Drug Discov. 2010 Aug;9(8):628-42

Authors: de Bodinat C, Guardiola-Lemaitre B, Mocaër E, Renard P, Muñoz C, Millan MJ

Current management of major depression, a common and debilitating disorder with a high social and personal cost, is far from satisfactory. All available antidepressants act through monoaminergic mechanisms, so there is considerable interest in novel non-monoaminergic approaches for potentially improved treatment. One such strategy involves targeting melatonergic receptors, as melatonin has a key role in synchronizing circadian rhythms, which are known to be perturbed in depressed states. This article describes the discovery and development of agomelatine, which possesses both melatonergic agonist and complementary 5-hydroxytryptamine 2C (5-HT2C) antagonist properties. Following comprehensive pharmacological evaluation and extensive clinical trials, agomelatine (Valdoxan/Thymanax; Servier) was granted marketing authorization in 2009 for the treatment of major depression in Europe, thereby becoming the first approved antidepressant to incorporate a non-monoaminergic mechanism of action.

PMID: 20577266 [PubMed - indexed for MEDLINE]

Wow that looks different (8/26/10

8/26/10

Driveway demo

Verbal learning differences in chronic mild traumatic brain injury, associated with changes on Diffusion Tensor Imaging and not often interpreted in standard neuropsychological assessment

Verbal learning differences in chronic mild traumatic brain injury

J Int Neuropsychol Soc. 2010 May;16(3):506-16

Authors: Geary EK, Kraus MF, Pliskin NH, Little DM

Following mild traumatic brain injury (TBI), a percentage of individuals report chronic memory and attention difficulties. Traditional neuropsychological assessments often fail to find evidence for such complaints. We hypothesized that mild TBI patients may, in fact, experience subtle cognitive deficits that reflect diminished initial acquisition that can be explained by changes in cerebral white matter microstructure. In the data presented here, a sample of nonlitigating and gainfully employed mild TBI patients demonstrated statistically significant differences from age and education matched control participants in performance on the first trial of a verbal learning task. Performance on this trial was associated with reduced fractional anisotropy in the uncinate fasciculus and the superior longitudinal fasciculus providing an anatomical correlate for the cognitive findings. Mild TBI patients were not impaired relative to control participants on total learning or memory composite variables. Performance on the first learning trial was not related to any psychological variables including mood. We concluded that patients with mild TBI demonstrate diminished verbal learning that is not often interpreted in standard neuropsychological assessment.

DHA helps heart and brain

Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline.

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Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline.

Curr Alzheimer Res. 2010 May 1;7(3):190-6

Authors: Yurko-Mauro K

Memory loss is a prominent health concern, second only to heart disease for older individuals. Docosahexaenoic acid (DHA), the principle omega-3 fatty acid in brain and heart, plays an important role in neural and cardiac function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly and Alzheimer's patients. Higher DHA intake and plasma levels are inversely correlated with increased relative risk of Alzheimer's disease (AD) and fatal coronary heart disease. DHA provides well known cardiovascular benefits (e.g. lower triglycerides, increased HDL cholesterol, decreased resting heart rate) in older adults. Preclinically, DHA supplementation restores brain DHA levels, enhances learning and memory tasks in aged animals, and significantly reduces beta amyloid, plaques, and tau in transgenic AD models. To date, clinical studies with DHA+EPA supplementation have shown some positive effects in mild cognitive impairment but not in AD, suggesting that early intervention may be a key factor to providing effective therapies. A recent clinical study examined individual effects of 900mg/d algal DHA as a nutritional supplement for age-related cognitive decline (ARCD). This randomized, double blind, placebo controlled study (n=485) found significantly fewer CANTAB Paired Associate Learning errors with algal DHA at six months versus placebo (diff. score -1.63+/-0.76, p=0.03). Positive effects on Verbal Recognition Memory (p<0.02) and significant decreases in resting heart rate with DHA (p<0.03) were observed, indicating improved learning and episodic memory functions and cardiovascular benefits for ARCD. Collectively, data reveal a potentially beneficial role for DHA in preventing or ameliorating cognitive decline and cardiovascular disease in the aged.

PMID: 20088810 [PubMed - indexed for MEDLINE]

More on DHA: http://search.medscape.com/medscape-search?newSearch=0&queryText=dha

Dan Gardner, M.D.

www.danielgardner.yourmd.com

dgardner@ucsd.edu  858-560-5609

Comprehensive Clinical Picture of Patients with Complicated vs Uncomplicated...

Comprehensive Clinical Picture of Patients with Complicated vs Uncomplicated Mild Traumatic Brain Injury.

via pubmed: (tbi imaging) and (s... by de Guise E, Lepage JF, Tinawi S, Leblanc J, Dagher J, Lamoureux J, Feyz M on 8/24/10

Comprehensive Clinical Picture of Patients with Complicated vs Uncomplicated Mild Traumatic Brain Injury.

Clin Neuropsychol. 2010 Aug 17;:1-18

Authors: de Guise E, Lepage JF, Tinawi S, Leblanc J, Dagher J, Lamoureux J, Feyz M

To compare the acute clinical profile of patients with uncomplicated vs complicated mild TBI (MTBI), socio-demographic and medical history variables were gathered for 176 patients diagnosed with MTBI and with (complicated, N = 45) or without (uncomplicated, N = 131) positive findings on cerebral imaging. Neurological examination, neuropsychological assessment and self-evaluation of post-concussive symptoms were done at 2 weeks post trauma. Patients with complicated MTBI were more likely to show auditory and vestibular system dysfunction. Surprisingly, the uncomplicated group reported more severe post-concussive symptoms than patients with positive CT scans. The groups showed no other difference in neurological, psychological, or cognitive outcome. A complete neurological examination should be done acutely in patients with MTBI to determine more specific follow-up required.

PMID: 20730678 [PubMed - as supplied by publisher]

Traumatic Brain Injury in Children and Adolescents: Surveillance for Pituitary Dysfunction

Norwood KW, Deboer MD, Gurka MJ, Kuperminc MN, Rogol AD, Blackman JA, Wamstad JB, Buck ML, Patrick PD 
Traumatic Brain Injury in Children and Adolescents: Surveillance for Pituitary Dysfunction. [JOURNAL ARTICLE]
Clin Pediatr (Phila) 2010 Aug 19.

Background. Children who sustain traumatic brain injury (TBI) are at risk for developing hypopituitarism, of which growth hormone deficiency (GHD) is the most common manifestation.
Objective. To determine the prevalence of GHD and associated features following TBI among children and adolescents. Study design. A total of 32 children and adolescents were recruited from a pediatric TBI clinic. Participants were diagnosed with GHD based on insufficient growth hormone release during both spontaneous overnight testing and following arginine/glucagon administration.
Results. GHD was diagnosed in 5/32 participants (16%). Those with GHD exhibited more rapid weight gain following injury than those without GHD and had lower levels of free thyroxine and follicle-stimulating hormone. Males with GHD had lower testosterone levels.
Conclusions. GHD following TBI is common in children and adolescents, underscoring the importance of assessing for GHD, including evaluating height and weight velocities after TBI. Children and adolescents with GHD may further exhibit absence or intermediate function for other pituitary hormones.

Welcome to Traumatic Brain Injury (TBI) Updates. This blog will focus on diagnosis and treatment of emotional, behavioral, and cognitive problems resulting from TBI.

To see more information on the psychiatric aspects of Traumatic Brain Injury , visit http://tinyurl.com/tbidg.

Dan Gardner, MD, DFAPA
Psychiatry, Psychoanalysis, Traumatic Brain Injury

www.danielgardner.yourmd.com