In this edition of the news review, homocysteinuria was significantly associated with Alzheimer’s Disease in women, more findings are reported from the Alzheimer’s Disease Neuroimaging Initiative, serum tau protein levels were associated with traumatic brain injury outcome, Insular cortex volumes were associated with progression to psychosis, benzodiazepine use in ITU was associated with subsequent depression and a number of related projects are underway which include making Transmission Electron Microscope images of the retina and brain available online for scientists to work on as well as the production of a 3-dimensional reconstruction of networks from these images.
Research in Dementia
A study looked at factors influencing length of time till admission to a nursing home for people with dementia and found that the characteristics of the care providers were important associations with time till admission (Habermann et al. 2009)(STT3). A combination of a logical memory test and the California Verbal Learning Test-II were found to be accurate in 87.5% of cases in discriminating cases of Mild Cognitive Impairment that converted to AD in this 4-year prospective study of 38 people with MCI (Rabin et al, 2009)(STT4). The Swedish Lund group have suggested an aggregate of MMSE scores, clock drawing test and 3D cube-copying test scores as indicating a further exclusion of Lewy Body Dementia on the basis of this study of 33 people with Lewy Body Dementia (Palmqvist et al, 2009)(STT4). People with AD or MCI were found to be impaired on a semantic fluency task relative to depressed and non-depressed controls (Lonie et al, 2009)(STT5). In a study of 21 people with vascular dementia, 79 people with AD and 352 controls there was found to be no significant difference between VaD and AD subjects on tests of prospective and retrospective memory (Livner et al, 2009)(STT5). A significant difference in cognitive profiles was found between people with mild AD and subcortical ischemic vascular dementia. In this study people with subcortical vascular dementia scored significantly worse on tests of visuospatial function and working memory (Kandiah et al, 2009)(STT4).
Diabetes was associated with a slower progression of Alzheimer’s Disease in this prospective Italian study of 154 people with mild-to-moderate AD and it will be interesting to see further replication (Musicco et al, 2009)(STT4). An association of Cerebral Amyloid Angiopathy with cerebral infarction and haemmorhage was inferred from a significant increase in silent white matter lesions compared to a control group without CAA (Kimberly et al, 2009)(STT4). Hippocampal atrophy was associated with a significant increase in the risk of progressive to dementia in 70 people undergoing Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease (Aybek et al, 2009)(STT4). A case of angiitis is reported in association with Alzheimer’s Disease (Annweiler et al, 2008)(STT5). In a prospective study of 67 people with Multiple Sclerosis and 28 controls, active inflammation was associated with neurodegeneration but the inflammatory response diminished in the later stages of the disease until neurodegeneration occurred at a similar rate to the control group (Frischer et al, 2009)(STT4). In a prospective Swedish study homocysteine levels were significantly associated with Alzheimer’s Disease in women (Zilberstein et al, 2009)(STT3).
Using data from subjects in a Mayo Clinic longitudinal registry and the Alzheimer’s Disease Neuroimaging Initiative (21 healthy controls, 32 people with amnestic MCI and 8 people with AD) amyloid deposition in AD (using PIB-uptake PET images) was found to proceed constantly but was not associated with clinical symptoms. However MRI determined brain atrophy (baseline image versus follow-up image comparison) was associated with clinical symptoms and the authors suggest that both imaging approaches are complementary (Jack et al, 2009)(STT4). Epsilon4-positive APOE4 genotype was associated with significantly increased PIB uptake in the frontal, temporal and parietal cortex compared tothe Epsilon4 negative genotype although no difference was identified in grey matter volume (Drzezga et al, 2009)(STT4). The APOE epsilon4 alelle was associated with frontal and temporal lobe atrophy in this small study of 15 people with Alzheimer’s Disease (AD) who were carriers and 14 non-carriers with AD (Pievani et al, 2009)(STT5). In a prospective study of 34 people with traumatic brain injury, outcome on the Glasgow Coma Scale at 6 months was significantly associated with serum tau protein levels on admission although further replication studies are needed (Liliang et al, 2009)(STT4). Significant variability in immunosorbent assays for Tau and Abeta in CSF exist across the world and the authors of this study have called for a standardisation of procedures (Verwey et al, 2009)(STT3). An in-vitro study provided evidence that alpha-synuclein’s N and C terminal domains were required for macrophage activation (Lee et al, 2009)(STT5).
Research in Schizophrenia
Age of onset of psychosis in families with more than one member with schizophrenia was found to have a significant heritable component in this study which included 717 families in Mexico and Central America (Hare et al, 2009). A swedish study looking at 3 birth cohorts and a using semi-structured interview showed a 1% prevalence of psychosis in non-demented people aged 70, 78 and 82 (Sigstrom et al, 2009)(STT3). In a study of 125 people with schizophrenia, physical activity levels were comparable to population norms although 70% were classed as being overweight and the authors suggest possible mechanisms to account for the difference in their sample (McLeod et al, 2009)(STT3). In a study of 35 people with schizophrenia, 15 had passivity symptoms and 20 did not. Those with passivity symptoms were significantly more likely to underestimate time durations (Waters and Jablensky, 2009)(STT5).
A retrospective study of 52 elderly inpatients treated with Aripiprazole showed documentation of side effects in 17% of cases and that agitation was the most common side-effect occurring in 8% of people (Coley et al, 2009)(STT3). Zolmitriptan was found to significantly improve neuroleptic-induced akathisia although not showing superiority to propranolol in this regards and the authors recommend a placebo-controlled trial (Avital et al, 2009)(STT5).
The authors of a systematic review of 33 structural MRI studies in people prescribed antipsychotics found evidence for an increased basal ganglia volume in people prescribed typical antipsychotics although other findings were less clear (Navari and Dazzan, 2009)(STT4). A relatively small prospective imaging study provided evidence of gray matter loss over a mean 1.8 year follow-up period in people with First Episode Psychosis (FEP) and those at ultra-high risk of developing psychosis (UHRNP). In both FEP and UHRP there was significant grey matter loss in the planum temporale and planum polare and in FEP there was also gray matter loss in the left Heschl gyrus which was significantly associated with delusional severity (Takahashi et al, 2009)(STT4). Grey matter volume in the Insular Cortex was reduced in a sample of 31 people at Ultra-High Risk of progression to psychosis who later progressed (UHR-P) when compared with 66 people with Ultra-High Risk who did not progress (UHRPNP). Longitudinally there was found to be a significant reduction in grey matter volume in the insular cortex bilateraly in the UHRP group compared to both controls and the UHRPNP group (Takahashi et al, 2009)(STT4).
A study in 34 people undergoing neurosurgical ablation of regions in the prefrontal cortex found evidence of social and emotional deficits on the ‘social-emotional questionnaire’ (Bramham et al, 2009)(STT5). A Canadian study which used data from the Canadian Community Health Survey looked at medication adherece in 6201 people prescribed psychotropic medication and estimated that non-adherence was 34.6% for antipsychotics and 45.9% for antidepressants and that the most frequent reason given was that of forgetfulness which also varied between the different types of psychotropic medication (Bulloch and Patten, 2009)(STT3).
News in Brief
Benzodiazepine use in people in the Intensive Care Unit has been associated with the subsequent development of depression. Problematic behaviours were identified in a Mayo Clinic study in one sixth of people with Parkinson’s Disease prescribed medication for their condition. Family therapy was associated with higher response rates in people with depression when compared with treatment as usual. A specialised visual training method known as eccentric training (which involves the use of peripheral vision) has been advocated for use in people with macular degeneration. Long-term health goals were associated with higher levels of self-control in health tasks in this study. A review of previous studies suggests that several brain regions are associated with wisdom although definitions of this term vary. Older adults were found more likely to recover functioning after admission for surgery than for medical illnesses in this study although further replication studies will be needed.
A lack of supportive social relationships at work was associated with burnout in this Swedish study. Evidence suggests that women who were classed as obese were underrepresented amongst CEO’s of businesses compared to men which the authors interpret as suggesting weight discrimination against women although studies with different methodologies will be needed to explore this hypothesis further.
Complex and exciting developments are underway in making Transmission Electron Microscope images of the brain and retina available to scientists around the world and also to integrate them into 3-dimensional models. The interaction of microglia with neurons has been published in a recent Japanese study in which it was found that microglia make contact with the synapses of a neuron regularly and for a usual duration of a few minutes.
A gene NOS1AP has been associated with schizophrenia in a study which used a new statistical method for establishing linkage. The structure of a plant protein similar to that of mammalian proteins involved in circadian rhythms has been identified with potential implications for therapeutic approaches to sleep disorders. A Lilly-funded study has provided evidence that a new technique known as Stable Isotope-Linked Kinetics is effective in identifying rates of A-Beta production which could be effective in identifying new therapies in Alzheimer’s Disease.
Annweiler C et al. 2008. Association of angiitis of central nervous system, cerebral amyloid angiopathy, and Alzheimers Disease: report of an autopsy case. Vasc Health Risk Manag.
Aybek S et al. Hippocampal atrophy predicts conversion to dementia after STN-DBS in Parkinson’s Disease. Parkinsonism Relat Disord. 2009.
Avital A et al. Zolmitriptan compared to propranolol in the treatment of acute neuroleptic-induced akathisia: A comparative double-blind study. Eur Neuropsychopharmacol. 2009. Epub.
Bramham J et al. Social and emotional functioning following bilateral and unilateral neurosurgical prefrontal cortex lesions. J Neuropsychol. 2009. 3(1). 125-43.
Bulloch A and Patten S. Non-adherence with psychotropic medications in the general population. Social Psychiatry and Psychiatric Epidemiology. 2009. Epub.
Coley K et al. Aripiprazole prescribing patterns and side effects in elderly psychiatric inpatients. J Psychiatr Pract. 2009. 15(2). 150-3.
Drzezga A et al. Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer Disease. Neurology. 2009. Epub.
Frischer J et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009. Epub.
Habermann S et al. Predictors of entering 24-h care for people with Alzheimer’s Disease: results from the LASER-AD study. Int J Geriatr Psychiatry. 2009. Epub.
Hare E et al. Heritability of age of onset of psychosis in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2009. Epub.
Jack C et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimers Disease: Implications for sequence of pathological events in Alzheimer’s Disease. Brain. 2009. Epub.
Kandiah N et al. Differences exist in the cognitive profile of Mild Alzheimer’s Disease and Subcortical Ischemic Vascular Dementia. Dement Geriatr Cogn Disord. 2009. 27(5). 399-403. Epub.
Kimberly W et al. Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology. 2009. 72(14). 1230-5.
Lee S et al. Identification of the amino acid sequence motif of alpha-synuclein responsible for macrophage activation. Biochem Biophys Res Commun. 2009. 381(1). 39-43.
Liliang P et al. Tau proteins in Serum predict outcome after severe traumatic brain injury. J Surg Res. 2009. Epub.
Livner A et al. Prospective and retrospective memory in Alzheimer’s Disease and Vascular Dementia: Similar patterns of impairment. J Neurol Sci. 2009. Epub.
Lonie J et al. Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer’s Disease. J Neuropsychol. 2009. 3(Pt 1). 79-92.
McLeod H et al. Base rates of physical activity in australians with schizophrenia. Psychiatry Rehabil J. 2009. 32(4). 269-75.
Musicco M et al. Predictors of progression of cognitive decline in Alzheimer’s Disease: the role of vascular and sociodemographic factors. J Neurol. 2009. Epub
Navari S and Dazzan P. Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med. 2009. 1-15. Epub.
Palmqvist S et al. Practical suggestions on how to differentiate dementia with Lewy bodies from Alzheimers Disease with common cognitive tests. Int J Geriatr Psychiatry. 2009. Epub.
Pievani M et al. Mapping the effect of APOE epsilon4 on gray matter loss in Alzheimer’s Disease in vitro. Neuroimage. 2009. 45(4). 1090-8.
Rabin L et al. Differential memory test sensitivity for diagnosing amnestic Mild Cognitive Impairment and predicting conversion to Alzheimer’s Disease. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2009. 1-20.
Sigstrom R et al. The prevalence of psychotic symptoms and paranoid ideation in non-demented population samples aged 70-82 years. Int J Geriatr Psychiatry. 2009. Epub.
Takahashi T et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry. 2009. 66(4). 366-76.
Takahashi T et al. Insular cortex gray matter changes in individuals at ultra-high risk of developing psychosis. Schizophrenia Research. Epub.
Verwey N et al. A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s Disease. Ann Clin Biochem. 2009. Epub.
Waters F and Jablensky A. Time discrimination deficits in schizophrenia patients with first-rank (passivity) symptoms. Psychiatry Rev. 2009. Epub.
Zylberstein D et al. Midlife homocysteine and late-life dementia in women. A prospective population study. Neurobiol Aging. 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.
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