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" />

Related Articles

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.

Related Articles

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