News Round-Up: April 2009 3rd Edition

In the news round-up this week, mild cognitive impairment was less likely to revert to no cognitive impairment if it had been confirmed on multiple occasions, different types of dementia were found to have recognisable and specific networks involved in the degenerative process, depression was associated with an increased risk of heart failure after an initial diagnosis of coronary artery disease and more evidence emerges for the therapeutic benefit of laughter.

Research in Dementia

The authors of a genome search meta-analysis of familial late-onset Alzheimer’s Disease identified a linkage with regions on chromosomes 1, 7 and 8 (Butler et al, 2009)(STT4). A 3-year follow-up study provided evidence that reversion to no cognitive impairment was more likely to occur if mild cognitive impairment had been assessed on a single occasion compared to cases where it had been identified on repeated testing (Loewenstein et al, 2009)(STT3). The researchers in an in-vitro study found that detected cholesterol levels in the cell membranes were significantly higher in older neurons compared to younger neurons and also provided evidence that lower cholesterol was associated with less vulnerability to Abeta mediated toxicity (Nicholson and Ferreira, 2009)(STT4). The authors of a meta-analysis of longitudinal epidemiological studies of risk factors for Alzheimer’s Disease identified obesity and diabetes as independent risk factors (Profenno et al, 2009)(STT3). There was found to be no significant difference between people with Alzheimer’s Disease and controls in brain-derived neurotrophic factor levels in a study with 196 people with equal numbers of controls and people with Alzheimer’s Disease (O’Bryant et al, 2009). Another study found an association between HDL and ABeta and the authors recommend a longitudinal replication study (Bates et al, 2009)(STT4). There is evidence that Zinc acts as a ligand at the metabotropic receptor (Besser et al, 2009)(STT5). The authors of a retrospective post-hoc study of Galantamine concluded that the optimal dose in mild Alzheimer’s Disease was 16mg/day (Aronson et al, 2009)(STT4).

News In Brief

A widely reported study in the Journal Neuron has shown that different types of dementia including Alzheimer’s Disease and behavioural variant Frontotemporal Dementia exhibit degeneration along neuronal networks and that the network is specific to the type of dementia. The researchers used MRI BOLD imaging which gives an approximation to regional cerebral blood flow. A pilot study of  a drug CPHPC has shown that it is effective in lowering the levels of serum amyloid P component (SAP) in the blood and the brain of people with Alzheimer’s Disease although follow-up studies will be required to assess the clinical implications (also reported here). An intriguing link has been found between proliferator-activated receptor coactivator 1 (a risk factor for diabetes type 2) and Alzheimer’s disease. The study shows that the gene product was decreased in Alzheimer’s Disease and may be related to processing of the Beta-Amyloid plaque. While diabetes is associated with a 2-fold increase in dementia prevalence, this study shows the heterogeneity that exists in the relationships between these two complex disorders. Episodes of hypoglycaemia were associated with an increased prevalence of dementia in this study. A new model of Alzheimer’s Disease has been developed and simulated on a computer. The model focuses on the the formation of the amyloid beta plaques and focuses on presenilin-1 and glycogen synthase kinase 3, proteins that have been implicated in Early-Onset Alzheimer’s Disease. The simulations suggests that neither protein results in disease alone but it is the combination which produces disease. Nevertheless such simulations may need to be followed up with biological studies to verify the predictions. The authors of a recent Cochrane review of relevant trials concluded that statins taken by study participants between the ages of 40 and 82 did not reduce the risk of dementia. The authors suggest that there may be different consequences for earlier administration of statins although that will require a further evaluation of relevant data. New evidence suggests that earlier experimental findings suggesting that the plaques in Alzheimer’s Disease produced calcium influx by thinning cellular membranes may instead have been an artefact produced by the use of a solvent in these studies – Hexafluoroisopropranolol. Research suggests that Huntington’s Disease is associated with a variety of changes (some of which related to glucose metabolism) that occur throughout the developmental period. Infrared tracking has been used to detect differences in duration of eye fixation on novel images in Mild Cognitive Impairment compared to controls which may have diagnostic utility. The authors of a Cochrane review of the use of PEG feeding in advanced dementia found no randomised controlled trials and concluded that there was no evidence to suggest improved survival or quality of life although one of the authors, Dr Sampson points out that cases are assessed individually while also noting assisted oral feeding as an alternative approach. The authors of a recent report looked at studies involving non-pharmacological approaches to managing Alzheimer’s Disease and found evidence of benefits for caregiver training and cognitive training although concluding that methodologies for these studies needed to be improved. APOE4 carriers aged 20-35 were found to have different patterns of activity in the hippocampus compared to controls using fMRI although longitudinal studies will likely be needed to examine the clinical relevance of these findings.

Developing depression after an initial diagnosis of coronary artery disease was associated with a 2-fold increased risk of heart failure in this study with an average follow-up period of 5.6 years. People with schizophrenia were found to be able to correctly discriminate hollow and normal faces in the ‘hollow-face paradigm in 94% of cases compared to 1% of controls. The authors identify this as evidence of a tendency towards ‘bottom-up processing’ in schizophrenia. A poll of 2000 people in England showed that many people are unaware of the calories contained within alcohol as reported here. A study has shown that cessation of drinking significantly influences survival rates in cirrhosis of the liver – for those continuing to drink – survival rates at 7 years was 44% compared to 72% in those who were abstinent. Another study in the BMJ and reported on here suggests that elderly people with strokes are undertreated. An association was found in an MRI study between aspirin and cerebral microbleeds in the elderly and this relationship will need to be explored in more detail given the various benefits associated with aspirin use. In another study, a trademarked system was effective in improving the dysarthria that developed after a stroke. A new type of shunting system is being developed following research into the flow of cerebrospinal fluid and this should have implications for hydrocephalus and a number of associated conditions. Exercises have been developed with reduced risk for aggravating Migraines.

A study has shown that synchronisation between breathing and heart rate alters in different stages of the sleep cycle and the techniques used in this study could be used in future sleep research. An interesting study provides evidence that we return our gaze to a previous target automatically unless we are actively searching from something (visually) in which case this action is inhibited. The authors of another study looked at the interaction between culture and mood and provided evidence that lowering mood resulted in stereotypical behaviour whilst exploratory behaviour resulted from elevating mood (mood was influenced by either music or modifying facial expressions). Evidence is provided to suggest that the brain processes vowels and consonants at different rates. Increasing ‘mirthful laughter‘ was associated with an increase in HDL in people with diabetes. The authors of a systematic review of the use of music in coronary heart disease patients concluded that music was associated with a significant reduction in heart rate and blood pressure.

References

Aronson S et al. Optimal dosing of galantamine in patients with mild or moderate Alzheimer’s Disease: post hoc analysis of a randomized, double-blind placebo-controlled trial. Drugs Aging. 2009. 26(3). 231-9.

Bates K et al. Association of cardiovascular factors and Alzheimer’s Disease plasma amyloid-beta protein in subject memory complainers. J Alzheimers Dis. 2009. Mar. Epub.

Besser L et al. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. J Neurosci. 2009. Mar. 29(9). 2890-901.

Butler A et al. Meta-analysis of linkage studies for Alzheimer’s Disease – A web resource. Neurobiol Aging. 2009. Epub.

Loewenstein D et al. Stability of different subtypes of Mild Cognitive Impairment among the Elderly over a 2 to 3-Year follow-up period. Dement Geriatr Cogn Disord. 2009. 27(5). 418-423.

Nicholson A and Ferreira A. Increased membrane cholesterol might render mature hippocampal neurons more susceptible to beta-amyloid-induced calpain activation and tau toxicity. J Neurosci. 2009. 29(14). 4640-51.

O’Bryant S et al. Brain-derived neurotrophic factor levels in Alzheimer’s Disease. J Alzheimers Dis. 2009. Mar. Epub.

Profenno L et al. Meta-analysis of Alzheimer’s Disease risk with obesity, diabetes and related disorders. Biol Psychiatry. 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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