News Round-Up: March 2009 4th Edition

In this news round-up, the Alzheimer’s Disease Imaging Initiative is already making an impact although the data acquisition phase is not yet fully complete, a Dutch prevention study halved incidence of depression and anxiety in those at risk, the memory impairment screen plus was effective in predicting conversion of Mild Cognitive Impairment to Alzheimer’s Disease, peak age for certain cognitive abilities averaged 22 years in one study and diabetes and LDL cholesterol levels were associated with progression rates in Alzheimer’s Disease.

Research in Psychosis

In a study involving 173 people with schizophrenia-like psychosis, schizophrenia spectrum disorders and depression and 64 controls looking at a number of measures including emotion and self-esteem, the best fitting model for paranoid delusions including pessimistic thinking style and impaired cognition as explanatory factors (Bentall et al, 2009)(STT4). In a sample of 451 85-year-olds in Sweden, paranoid symptoms were associated with agitation and irritability/anger in people with and without dementia and the authors emphasise the importance of treating these symptoms (Ostling et al, 2009)(STT3). The neurobiology of affiliation is an area with a number of implications for psychiatric disorders and is covered in this paper (Bora et al, 2009). A causal model for drug-induced diabetes is proposed in this paper (Starenburg and Bogers, 2009)(STT4). In a retrospective case-note review of 89 people started on Aripiprazole and 132 people started on Quetiapine over 5 years, improvement using Clinical Global Impression scores was broadly similar with 74% improving with Aripiprazole and 67% with Quetiapine (Shajahan et al, 2009)(STT4). A retrospective cohort study of 6957 national service conscripts showed an association between lower performance on a national examination given at the end of 6 years of primary education and development of schizophrenia spectrum disorders (Chong et al, 2009)(STT4).

Research in Mood Disorders

A prevention program in the Netherlands involving CBT Bibliotherapy, watchful waiting, CBT problem-solving treatment and referral for medication as necessary halved the incidence of depression and anxiety in a sample of 170 people over the age of 75 with subthreshold anxiety and depression (van’t Veer-Tazelaar et al, 2009)(STT3). Using Magnetic Transfer Ratios (a measure of white matter integrity), 16 people with type II diabetes and depression were found to have significantly lower MTR’s bilaterally in the head of the caudate compared with 22 people with type II diabetes without depression and a control group with diabetes or depression (Kumar et al, 2009)(STT5). A blunted prolactin and cortisol response to clomipramine infusion was found in people with remitted depression and a history of major affective disorders compared to a control group (Cordes et al, 2009)(STT5). In an RCT with 60 people with unipolar depression being treated with Imipramine, zinc supplementation was found to increase the speed of onset of response and efficacy and it will be interesting to see the results of further replication studies (Siwek et al, 2009)(STT4). In a deep brain stimulation study which involved 2 subjects, stimulation of the caudate nucleus was found to be effective for OCD symptoms and simulation of the nucleus accumbens was found to be effective for improving depressive symptoms and this larger studies are indicated (Aouizerate et al, 2009)(STT5).

Research in Dementia

A Dutch Randomised Controlled Trial found that a multidisciplinary diagnostic approach was cost-effective for evaluation of cognitively impaired elderly (Wolfs et al, 2009)(STT3). Using data from 383 MR volumes in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and MR based shape analysis, subjects with MCI and Alzheimer’s Disease were found to have an outward-deformation in the lateral ventricles. There was also evidence of inward deformation in the anterior-lateral and ventro-lateral thalamus (Qiu et al, 2009)(STT4). As cognition became increasingly impaired using study data from two trials, there was found to be worse agreement between three measures of cognition – Alzheimer’s Disease Assessment Scale – Cognitive, Clinical Dementia Rating and MMSE (Tractenberg et al, 2009)(STT4). An in vitro study provided evidence for neuroprotective effects of acetaminophen (Tripathy and Grammas, 2009)(STT5). In a secondary analysis in the Video-imaging Synthesis of Treating Alzheimer’s Disease (VISTA) study, 74% of community-resident people with mild-to-moderate AD were found to misplace items recurrently and for 81% of these cases, this represented the inability to recall where items had been placed (Hamilton et al, 2009)(STT4).

A causal relationship to explain the association between Alzheimer’s Disease and glaucoma has been proposed as reduced cerebrospinal fluid pressure by a Belgian group (Wostyn et al, 2009)(STT5). A component of inclusion bodies – trans-activation-responsive DNA-binding protein 43 (TDP-43) has been found in familial British Dementia by a Canadian group (Schwab et al, 2009)(STT4). The Memory Impairment Screen Plus (MISplus) was found to be more effective at predicting conversion of MCI to AD than a number of other measures including the MMSE when a threshold score of 2/6 was used in this longitudinal study (Dierckx et al, 2009)(STT3). Reduced whole-brain cortical thickness and DTI measurements in the left temporal region were effective in differentiating people with MCI and controls particularly in combination (Wang et al, 2009)(STT3). The clinical dementia rating scale and neuropsychological criteria were discordant for diagnosis of MCI in 37% of cases in a study of 3063 elderly people with dementia living in the community (Saxton et al, 2009)(STT4). Although performance on tests wasn’t impaired by drinking caffeine containing drinks (ccd’s) there was found to be a linearly decreasing performance with an increase in age in those consuming ccd’s before the test and the authors caution that ccd’s should be considered when interpreting test scores (Lesk et al, 2009)(STT4). Placing of the minute hand on the clock drawing test was effective in discriminating people with Alzheimer’s Disease from controls (Leyhe et al, 2009)(STT3). A combination of folate and B12 deficiency was found to increase apoptosis and intracellular homocysteine to a greater extent than either alone in this in vitro study (Kifle et al, 2009)(STT5). In the Lothian Birth Cohort 1936 study, APOE4 carrier study was found to interact with childhood intelligence in influencing old age non-verbal cognition (Luciano et al, 2009)(STT4).

News in Brief

The DISC 1 gene which is associated with Schizophrenia has been found to influence neural development and other relevant genes in two recent studies. A class of drugs – the secretase inhibitors – that are being trialled for Alzheimer’s Disease have been found to reduce traumatic brain injury related damage. A study in the new field of optogenetics suggests that deep brain stimulation in Parkinson’s Disease may be more effective when applied to the axons rather than the cell bodies of neurons in the subthalamic nucleus. Using a paradigm which involves fluorescence – FRET, a research team has found that alpha-synuclein which is implicated in Parkinson’s Disease is able to rapidly change shape. Alpha-synuclein is a member of a class of proteins – the ‘intrinsically disordered proteins’ which remain functional even when unfolded and which challenge the notion of a fixed 3-d protein structures always correlating with function. An exciting research project is 95% complete – the Alzheimer’s Disease Neuroimaging Initiative involves longitudinal MRI and PET scans as well as a number of other biological markers and the data is being made publicly available. A small study provides further evidence that hippocampal volume and rate of atrophy are associated with development of Alzheimer’s Disease. Diabetes and elevated LDL cholesterol levels have been associated with higher rates of progression in Alzheimer’s Disease in a longitudinal study involving 156 people with Alzheimer’s Disease. It will be interesting to see the results of larger replication studies. Inhibition of CK2 (a transport regulating enzyme) was found to interfere with the effect of Amyloid protein on tau transport in neurons. In a widely discussed study a peak age of 22 was found for cognitive abilities such as abstract reasoning and processing speed.

One study has looked at how scientific knowledge increases by focusing on yeast research. The researchers found that knowledge grew exponentially and that scientists (both junior and senior) working in large teams were less ‘productive’. Prevalence of depression in epilepsy was found to be increased almost two-fold in the Canadian Community Health Survey. Indirect evidence suggests that low-moderate levels of alcohol influence the release of beta-endorphins in the ventral tegmental area. The authors of a small study found that people with depression were less able to learn beneficial information in a special test of novel attitudes although it would be interesting to see further replication in larger samples.

The authors of an analysis of 57 prospective studies involving 900,000 people conclude that moderate obesity (BMI 30-35) reduces lifespan by an average of 3 years and severe obesity (BMI 40-50) reduces lifespan by an average of 10 years. A small study examined the association between anxiety levels in jurors and the nature of material being discussed in the trial and suggested that women could be more prone to anxiety in the trials particularly if they had experienced similar events in their own history. However further replication is needed. QTC intervals have been used correlated with post-CVA mortality in one study. Cells derived from a tumour have been used to create neurospheres which are now being used in neuroscience research. High-angular resolution diffusion imaging was used in twins to suggest that genetics determine myelin integrity in a number of important brain regions. Since myelin influence nerve conduction velocities and this is associated with speed of processing which in turn is associated with intelligence, myelin genes have been suggested to be related to intelligence. The SIRT1 gene and NAD a metabolite for energy production have been linked in a new study. NAD is needed for SIRT1  function and levels of NAD in cells oscillates daily. SIRT1 is conserved across organisms and is implicated as a contributing factor in the aging process. Synchronisation of EEG activity was found in guitarist playing music together. A preliminary study suggests that Trigeminal Nerve Stimulation may be effective in intractable epilepsy.

Abbreviations

AD Alzheimer’s Disease

LDL Low Density Lipoprotein

MMSE Mini-Mental State Examination

MR Magnetic Resonance

MCI Mild Cognitive Impairment

References

Aouizerate B et al. Distinct striatal targets in treating obsessive-compulsive disorder and major depression. J Neurosurg. 2009. Epub.

Bentall R et al. The Cognitive and Affective Structure of Paranoid Delusions. Arch Gen Psychiatry. 2009. 66(3). 236-247.

Bora E, Yucel M and Allen N. Neurobiology of human affiliative behaviour: implications for psychiatric disorders. Curr Opin Psychiatry. 2009. Epub.

Chong S et al. Academic attainment: a predictor of psychiatric disorders. Soc Psychiatry Psychiatr Epidemiol. 2009. Epub

Cordes J et al. Abnormal neuroendocrine response to clomipramine in hereditary affective psychosis. Depress Anxiety. 2009. Epub.

Dierckx E et al. Verbal cued recall as a predictor of conversion to Alzheimer’s Disease in Mild Cognitive Impairment. Int J Geriatr Psychiatry. 2009.

Hamilton L et al. Misplacing objects in mild to moderate Alzheimer’s Disease: A descriptive analysis from the VISTA clinical trial. J Neurol Neurosurg Psychiatry. 2009. Epub.

Kifle L et al. Deprivation of folate and B12 increases neurodegeneration beyond that accompanying deprivation of either vitamin alone. J Alzheimers Dis. 2009. 16(3). 533-540.

Kumar A et al. Focal subcortical biophysical abnormalities in patients diagnosed with type 2 diabetes and depression. Arch Gen Psychiatry. 2009. 66(3). 324-330.

Leyhe T et al. The minute hand phenomenon in the clock test of patients with early Alzheimer’s Disease. J Geriatr Psychiatr Neurol. 2009. Epub.

Lesk V et al. The effect of recent consumption of caffeine-containing foodstuffs on neuropsychological tests in the elderly. Dement Geriatr Cogn Disord. 2009. 27(4). 322-328.

Luciano M et al. Cognitive ability at age 11 and 70 years, information processing speed and APOE variation: The Lothian Birth Cohort 1936 study. Psychol Aging. 2009. 24(1). 129-38.

Ostling S et al. Psychotic and behavioural symptoms in a population-based sample of the very elderly subjects. Acta Psychiatr Scand. 2009. Epub.

Qiu A et al. Regional shape abnormalities in mild cognitive impairment and Alzheimer’s Disease. Neuroimage. 2009. 45(3). 656-61.

Saxton J et al. Functional and cognitive criteria produce different rates of MCI. J Neurol Neurosurg Psychiatry. 2009. Epub.

Schwab C et al. TDP-43 pathology in familial British Dementia. Act Neuropathol. 2009. Epub.

Shajahan P et al. Comparing the effectiveness of aripiprazole and quetiapine in schizophrenia and related psychoses: a naturalistic, retrospective chart review study. J Clin Psychiatry. 2009. Epub.

Siwek M et al. Zinc supplementation augments efficacy of imipramine in treatment resistant patients: A double blind, placebo-controlled study. J Affect Disord. 2009.

Starrenburg F and Bogers J. How can antipsychotics cuase diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins. Eur Psychiatry. 2009. Epub.

Tractenberg R and Aisen P. Agreement in Cognitive and Clinical Assessments in Alzheimer’s Disease. Dement Geriatr Cogn Disord. 2009. 27(4). 344-352.

Tripathy D and Grammas P. Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress. J Neuroinflammation. 2009. 6(1). 10. Epub.

Van’t Veer-Tazelaar M et al. Stepped-care prevention of Anxiety and Depression in Late Life. A Randomized Controlled Trial. Arch Gen Psychiatry. 2009. 66(3). 297-304.

Wang L et al. Alterations in cortical thickness and white matter integrity in Mild Cognitive Impairment measured by whole-brain cortical thickness mapping and diffusion tensor imaging. AJNR Am J Neuroradiol. 2009.

Wolfs C et al. Economic evaluation of an integrated diagnostic approach for psychogeriatric patients. Results of a Randomized Controlled Trial. Vol 66(3). 313-323. 2009.

Wostyn P et al. Alzheimer’s Disease and glaucoma: Is there a causal relationship? B J Opthalmology. 2009. Epub.

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

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