Category specific deficits in Alzheimer's disease: fact or artefact?

Impairments in semantic memory commonly occur in Alzheimer's Disease (AD) but do these occur along category-specific lines? We administered a confrontation naming task comprising living and nonliving items to 68 individuals with AD and 59 age-matched control participants, in a study designed to address some of the methodological issues affecting investigation of category effects. In Experiment 1, stimuli were matched for familiarity and word frequency and also visual complexity, and the AD group showed a differential deficit in nonliving things. In Experiment 2, however, living and nonliving stimuli were matched for age-of-acquisition, name agreement, word frequency, and naming accuracy of elderly controls and there was no categorical impairment in the AD group. The AD group was subdivided first into mild and moderate AD, and then into normal or impaired overall naming groups and performance was reanalysed, but there was still no significant category deficit in any group. Converging evidence was provided by hierarchical regressions across items, as age-of-acquisition, name agreement and word frequency were significant predictors of naming performance in mild and moderate AD groups, but category was not. In Experiment 3, stimulus items were matched for familiarity and naming accuracy of elderly controls when their performance was off-ceiling, and again no differential effect of category was found. When we reduced slightly how closely matched stimuli were for familiarity we then found a differential impairment in living things in the AD group. When reviewing the changing pattern of results from use of different stimulus sets, we concluded that the main determinant of whether or not a categorical impairment of either sort is found in AD is which stimulus properties are controlled during stimulus selection. We conclude that AD does not generally lead to a selective category loss in semantic knowledge.     

Depression and epilepsy: A bidirectional relation?

A bidirectional relation between depressive disorders and epilepsy has been suggested by several population-based studies and is supported by experimental studies. This article reviews the potential pathogenic mechanisms operant in both disorders that may explain such a relation. These mechanisms include a hyperactive hypothalamic-pituitary-adrenal (HPA) axis and its neuroanatomic and neuropathologic complications, as well as disturbances in serotonergic, noradrenergic, γ-aminobutyric acid (GABA)ergic and glutamatergic neurotransmitter systems, all of which may be interrelated.     

Depression and stroke: cause or consequence?

Depression after stroke is common. Although different opinions exist about the definition, diagnosis, and measurement of outcomes related to depression after stroke, there is little debate about the prevalence of depression symptoms and their impact on stroke survivors and their families. Depression after stroke has long been recognized as a common condition with many negative effects in the poststroke period, but more recently depression has also been identified as an independent stroke risk factor. Given that there are at least 500,000 new ischemic strokes yearly in the United States, a conservative estimate is that 150,000 U.S. stroke survivors develop poststroke depression each year. Because effective treatments exist but are likely underutilized for depression, this is an important example of an evidence-practice gap to which increased efforts to improve care should be made. Such efforts would likely improve not only patient symptoms but may also decrease stroke risk, influence stroke functional recovery, decrease mortality, and reduce poststroke health care utilization. This article provides an overview of depression diagnosis in stroke, reviews the epidemiology of poststroke depression and its associated morbidity and mortality, and reviews existing evidence on the treatment and prevention of poststroke depression.     

Nonsuicidal self-harm and suicide attempts in adolescents: differences in kind or in degree?

Purpose

The purpose of the present study was to measure the prevalence of self-harm (SH) behaviours and examine potential differences in characteristics among adolescents reporting on self-harm (SH), depending on whether they had attempted suicide (SA), performed nonsuicidal self-harm (NSSH), or both.

Methods

Cross-sectional survey of 11,440 adolescents aged 14–17 years in the city of Oslo, Norway. Responses regarding measures of lifetime SH and risk factors were collected. The response rate was 92.7 %. Data were analysed by segregating SH responses into the categories of NSSH, SA, and NSSH + SA.

Results

Among all respondents, 4.3 % reported NSSH, 4.5 % reported SA, 5.0 % reported both NSSH and SA, and 86.2 % reported no SH. The group reporting to have engaged in both behaviours comprised more girls and reported more suicidal ideation, problematic lifestyles, poorer subjective health, and more psychological problems compared with the other groups. The four groups could be distinguished by one discriminant function that accounted for most of the explained variance.

Conclusions

Our findings suggest that NSSH and SA are parts of the same dimensional construct in which suicidal ideation carries much of the weight in adolescents from a school-based sample. They also indicate the group of adolescents who seems to alternate between NSSH and SA is more burdened with mental ill-health and behavioural problems compared with others. These adolescents should therefore be targeted by clinicians and school health personnel for identification and provision of adequate help and services.     

Oligomers, fact or artefact? SDS-PAGE induces dimerization of β-amyloid in human brain samples

The formation of low-order oligomers of β-amyloid (Aβ) within the brain is widely believed to be a central component of Alzheimer’s disease (AD) pathogenesis. However, despite advances in high-throughput and high-resolution techniques such as xMAP and mass spectrometry (MS), investigations into these oligomeric species have remained reliant on low-resolution Western blots and enzyme-linked immunosorbent assays. The current investigation compared Aβ profiles within human cortical tissue using sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE), xMAP and surface enhanced laser desorption/ionization time-of-flight MS and found that whilst there was significant correlation across the techniques regarding levels of monomeric Aβ, only SDS-PAGE was capable of detecting dimeric isoforms of Aβ. The addition of synthetic di-tyrosine cross-linked Aβ_1–40Met₃₅(O) to the AD tissue demonstrated that the MS methodology was capable of observing dimeric Aβ at femto-molar concentrations, with no noticeable effect on monomeric Aβ levels. Focus turned to the association between SDS-PAGE and levels of observable dimeric Aβ within the AD brain tissue. These investigations revealed that increased levels of dimeric Aβ were observed with increasing concentrations of SDS in the sample buffer. This finding was subsequently confirmed using synthetic Aβ_1–42 and suggests that SDS was inducing the formation of dimeric Aβ. The findings that SDS promotes Aβ dimerization have significant implications for the putative role of low-order oligomers in AD pathogenesis and draw into question the utility of oligomeric Aβ as a therapeutic target.     

Neurogenesis and Depression: Breakthrough or Blind Alley?

Pieces of evidence are emerging in support of the startling idea that the birth of new neurones in the adult brain in some way underlies major depression. Although there are intriguing parallels between factors that regulate neurogenesis and those predicting depression or its recovery, at this point, we should remain sceptical but allow cautious hope that more effective therapies may be suggested.     

Depression in multiple sclerosis: reactive or endogenous?

Multiple sclerosis is associated with high rates of depression. The extent to which this is related to living with chronic illness or part of the disease process remains unclear. This question was investigated by comparing rates of depression in MS with those in rheumatoid arthritis, which involves similar physical and psychosocial stressors but without central nervous system involvement. The study involved an on-line survey, which included measures of depression not confounded by somatic symptoms, medication use, self-reported physical functioning, pain, and other demographic variables. Results indicated that disease group (multiple sclerosis, rheumatoid arthritis) independently predicted depression above and beyond demographic and disease-related variables. Results support the hypothesis that depression in MS is partly determined by direct neurological consequences of the condition.     

Depression and Alzheimer's disease: symptom or comorbidity?

Alzheimer's disease is the most frequent form of dementia, where behavioral and cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported by caregivers. Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer's disease. Cognitive impairment was equally distributed among the subjects. Patients, aged 68 to 76 years old, were randomized to receive inhibitors of cholinesterase (Donepezil, 5 mg/day) alone, or inhibitors of cholinesterase plus selective serotonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We followed up all the patients for one year, with particular concern for neuropsychological aspects associated with eventual behavioral changes. Results indicate that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients and caregivers. Side effects in both groups were few, and there were no study withdrawals. This paper discusses the relationship between dementia and depression, and presents our finding that depressive symptoms, if specifically treated, tend to reduce caregiver stress and improve well-being in patients with Alzheimer's disease.     

Mossy cells in epilepsy: rigor mortis or vigor mortis?

Mossy cells are bi-directionally connected through a positive feedback loop to granule cells, the principal cells of the dentate gyrus. This recurrent circuit is strategically placed between the entorhinal cortex and the hippocampal CA3 region. In spite of their potentially pro-convulsive arrangement with granule cells, mossy cells have not been seriously considered to promote seizures, because mossy cells, allegedly one of the most vulnerable cell types in the entire mammalian brain, have long been 'known' to die en masse in epilepsy. However, new data suggest that rumors of the rapid demise of the mossy cells might have been greatly exaggerated.