Lewy body variant of Alzheimer's disease: selective neocortical loss of t-SNARE proteins and loss of MAP2 and alpha-synuclein in medial temporal lobe.

Lewy bodies (LBs) appear in the brains of nondemented individuals and also occur in a range of neurodegenerative disorders, such as dementia with Lewy bodies (DLB) and Parkinson's disease. A number of people with a definite diagnosis of Alzheimer's disease (AD) also exhibit these intraneuronal inclusions in allo- and/or neocortical areas. The latter, referred to as Lewy body variant of AD (LBV), bears a clinical resemblance to AD in terms of age at onset, duration of illness, cognitive impairment, and illness severity. Since the presence of LBs is accompanied by neuronal cytoskeleton changes, it is possible that the latter may influence neuronal connectivity via alterations to the synaptic network. To address this, we examined the expression of synaptic proteins (synaptophysin, syntaxin, SNAP-25, and alpha-synuclein) and two cytoskeletal proteins (tau and MAP2) in the brain tissue of subjects enrolled in a population-based autopsy study (n = 47). They were divided into groups with no memory problems (control group, n = 15), LBV (n = 5), AD devoid of LBs (n = 17), cerebrovascular dementia (n = 3), and mixed dementia (n = 7). The LBV and AD groups had a similar degree of cognitive impairment and neuropathological staging in terms of Braak staging and CERAD score. In comparison with the control group and the dementia groups without LBs, the LBV group had significantly lower levels of syntaxin and SNAP-25 (23%) in the neocortex, and depletion of MAP2 (64%), SNAP-25 (34%), and alpha-synuclein (44%) proteins in the medial temporal lobes. These findings suggest that the t-SNARE complex deficit present in LBV may be associated with the presence of LB-related pathology and may explain the more profound cholinergic loss seen in these patients.

Basic concepts of depression.

This paper reviews concepts of depression, including history and classification. The original broad concept of melancholia included all forms of quiet insanity. The term depression began to appear in the nineteenth century, as did the modern concept of affective disorders, with the core disturbance now viewed as one of mood. The 1980s saw the introduction of defined criteria into official diagnostic schemes. The modern separation into unipolar and bipolar disorder was introduced following empirical research by Angst and Perris in the 1960s. The partially overlapping distinctions between psychotic and neurotic depression, and between endogenous and reactive depression, started to generate debate in the 1920s, with considerable multivariate research in the 1960s. The symptom element in endogenous depression currently survives in melancholia or somatic syndrome. Life stress is common in various depressive pictures. Dysthymia, a valuable diagnosis, represents a form of what was regarded earlier as neurotic depression. Other subtypes are also discussed.

Cohort differences in disease and disability in the young-old: findings from the MRC Cognitive Function and Ageing Study (MRC-CFAS).

BACKGROUND: Projections of health and social care need are highly sensitive to assumptions about cohort trends in health and disability. We use a repeated population-based cross-sectional study from the Cambridgeshire centre of the UK Medical Research Council Cognitive Function and Ageing Study to investigate trends in the health of the young-old UK population METHODS: Non-overlapping cohorts of men and women aged 65-69 years in 1991/2 (n = 689) and 1996/7 (n = 687) were compared on: self-reported diseases and conditions; self-rated health; mobility limitation; disability by logistic regression and four-year survival by Cox Proportional Hazards Regression models, with adjustments for differences in socio-economic and lifestyle factors. RESULTS: Survival was similar between cohorts (HR: 0.91, 95% CI: 0.62 to 1.32). There was a significant increase in the number of conditions reported between cohorts, with more participants reporting 3 or more conditions in the new cohort (14.2% vs. 10.1%). When individual conditions were considered, there was a 10% increase in the reporting of arthritis and a significant increase in the reporting of chronic airways obstruction (OR: 1.36, 95% CI: 1.04 to 1.78). CONCLUSION: This study provides evidence of rising levels of ill-health, as measured by the prevalence of self-reported chronic conditions, in the newer cohorts of the young-old. Though changes in diagnosis or reporting of disease cannot, as yet, be excluded, to better understand whether our findings reflect real increases in ill-health, investment should be made into improved population-based databases, linking self-report and objective measures of health and function, and including those in long-term care.

Size and burden of depressive disorders in Europe.

We review epidemiological studies of depression in Europe. Community surveys are essential. Methodological differences in survey methods, instruments, nuances in language and translation limit comparability, but consistent findings are emerging. Western European countries show 1 year prevalence of major depression of around 5%, with two-fold variation, probably methodological, and higher prevalences in women, the middle-aged, less privileged groups, and those experiencing social adversity. There is high comorbidity with other psychiatric and physical disorders. Depression is a major cause of disability. Incidence has been less studied and lifetime incidence is not clear, with longitudinal studies required. There is pressing need for prevalence studies from Eastern Europe. The considerable differences in health care systems among European countries may impact on proportions of depressives receiving treatment and its adequacy, particularly in the key area of primary care, and require further study. There is a need for public health programmes aimed at improving treatment, reducing rates and consequences of depressive disorders.

Cognitive therapy in relapse prevention in depression.

This paper reviews recent advances in application of cognitive therapy (CBT) to a therapeutic problem in depression. Modern follow-up studies indicate that, in spite of the efficacy of pharmacotherapy, relapse and recurrence rates in some depressed patients remain high. This does not appear mainly due to failure to receive medication, but to reflect intractability of the disorder. In acute treatment, psychological treatments, although beneficial, are less cost-effective than antidepressants, due to high costs of therapists. Benefit which lasts longer, particularly if combined with medication, may therefore be particularly valuable. There have now been seven randomized controlled trials of cognitive therapy designed specifically to test relapse and recurrence prevention. All have shown significant benefit, which lasts beyond the cessation of therapy. The effect appears to be more on preventing symptom return than on lessening current symptoms, to summate well with continuation and maintenance antidepressant, and not to be due simply to enhanced medication adherence. Incorporation into routine clinical practice is now appropriate and recommendations are proposed.

Depression: major problem for public health.

The aim of this Editorial is to discuss depression as an important disorder for public health. The literature regarding epidemiology, consequences, adequacy of service delivery and prevention of depression is reviewed. Depression is a common disorder with high lifetime rates, particularly in women, and those experiencing social adversity. It is a major cause of disability, and causes death both by suicide and due to raised rates of physical disorders. Many cases are undiagnosed and treatment is often inadequate. Primary prevention is not yet easily feasible but secondary prevention by earlier recognition, public and professional education, can produce benefits. There is a need for public health programmes aimed at improving recognition, treatment, and reducing consequences.

Sub-syndromal and syndromal symptoms in the longitudinal course of bipolar disorder.

BACKGROUND: There have been few detailed longitudinal symptom studies of bipolar disorder. AIMS: To describe the course of bipolar disorder over 18 months in 204 patients receiving mental healthcare. METHOD: Patients were interviewed every 8 weeks, with weekly ratings of depression, mania and overall severity. RESULTS: Participants were symptomatic 53% of the time, with sub-syndromal symptoms present for twice as long as major disorder, and depressive symptoms three times more than manic symptoms. Individuals who were experiencing an episode at baseline spent 33% of the 18 months with substantial sub-syndromal symptoms, 17% with major disorder and 28% symptom free. Those not experiencing a baseline episode spent twice as long symptom free and half as long at disorder levels. Changes in symptom level were frequent. Predictors of sub-syndromal symptoms were similar to those of major disorder. CONCLUSIONS: Sub-syndromal residual symptoms are an important problem in recurrent bipolar disorder and require therapeutic intervention.

Mood disorders: review of current diagnostic systems.

In their sections on mood disorders, both ICD-10 and DSM-IV represent considerable advances on ICD-9 in drawing affective disorders together in one section, distinguishing bipolar disorder from unipolar, including dysthymia and using clear definitions. Problems with ICD-10 include complexity, use of different clinical and research definitions, emphasis on single versus recurrent episodes and the lack of some clinically useful subtypes. DSM-IV is less complex but assigns separate unjustified categories of medical and substance-induced mood disorders, and fails to code its useful qualifiers. Both classifications preserve categories for psychotic depression and melancholia/somatic syndrome, which are better coded in ICD-10. The severity distinctions could usefully be extended to a milder category of minor depression. It is also recommended that the two classifications be brought together, with small differences in definitions ironed out and a single set used both clinically and for research, the simpler DSM-IV organisation, the omission of the categorisations of single versus recurrent and mood disorder due to general medical or substance abuse disorders, and the inclusion of coding for some subtypes such as seasonal and postpartum.

Longitudinal syndromal and sub-syndromal symptoms after severe depression: 10-year follow-up study.

BACKGROUND: Few follow-up studies of depression have evaluated depressive symptomatology over time at both threshold and sub-threshold levels. AIMS: To evaluate long-term longitudinal symptomatic course after an episode of severe depression. METHOD: A total of 61 participants from a previous study cohort underwent a detailed interview covering the longitudinal course of depression and pharmacological treatment over 8-11 years of follow-up. RESULTS: Of the follow-up months, 52% were spent at an asymptomatic level, 15% at minor symptom level, 20% at residual symptom level and 13% at full depression level. Also, 30% of follow-up months were spent in an episode of depression, and 18% of patients never achieved asymptomatic status during follow-up. The percentage of patients at each symptom level remained relatively stable after the first 2 years, but levels in individuals fluctuated, with a mean of two changes in symptom levels per follow-up year. CONCLUSIONS: After severe episodes, sub-syndromal levels of depression are common and persistent, with considerable fluctuation suggesting a continuum between sub-syndromal subtypes and full depression.