Vascular Cognitive Disorder.

The term vascular cognitive disorder (VCD) refers to a heterogeneous group of disorders in which the primary feature is cognitive impairment attributable to cerebrovascular disease (CVD). This includes not only vascular dementia (VaD) but also cognitive impairment of insufficient severity to meet diagnostic criteria for dementia. VCD is recognized as the second most common cause of dementia after Alzheimer's disease (AD), but prevalence rates vary widely according to the diagnostic criteria employed. There have been recent attempts to standardize diagnostic criteria. VCD incorporates a range of neuropathological mechanisms including poststroke impairment, small and large vessel disease, and cases of mixed-pathology, with CVD interacting with AD and other neuropathologies. Recent neuroimaging data have improved our understanding of the etiology of VCD. Symptomatic treatments for VaD have modest benefit and there is increased focus on the primary and secondary preventative benefits of vascular risk factor control.

The relationship of cerebral microbleeds to cognition and incident dementia in non-demented older individuals.

Cerebral microbleeds (CMB), suspected markers of hemorrhage-prone microangiopathy, are common in patients with cerebrovascular disease and in those with cognitive impairment. Their longitudinal relationship with cognitive decline and incident dementia in non-demented community-dwelling older individuals has been insufficiently examined. 302 adults aged 70-90 participating in the population-based Sydney Memory and Ageing Study underwent a susceptibility-weighted imaging (SWI) MRI sequence. The relationship of CMB with performance on neuropsychological tests was examined both cross-sectionally and longitudinally, over a mean of 4 years. The association with cases of incident dementia during this period was also examined. The prevalence of CMB was 20%. In cross-sectional analysis, after adjusting for demographics and vascular risk factors, there was a significant association between the presence of CMB and poorer executive function. CMB were not associated with global cognition or other cognitive domains. On longitudinal analysis, after adjusting for demographics and vascular risk factors, there was a greater decline in visuospatial ability in those with CMB compared to those without. The presence of CMB was not associated with increased progression to dementia. CMB are associated with impairments in specific cognitive domains: executive function and decline in visuospatial ability, independent of other markers of CVD including white matter hyperintensities. This suggests a direct contribution of CMB to cognitive impairment although no significant difference in incident dementia rates was observed.

Caregiver burden in mild cognitive impairment.

OBJECTIVES: We aimed to compare the rates of burden amongst caregivers of participants with mild cognitive impairment (MCI), compared to a control group. We also aimed to identify factors in both the caregiver and patient that are associated with significant levels of burden. METHOD: This was a cross-sectional study. Sixty-four participants with MCI, 36 control-participants and their respective caregivers/informants were recruited to a university research clinic. The proportion of those who showed clinically significant levels of burden was determined by a Zarit Burden Interview score of >21. The associations of burden in MCI-caregivers were calculated in the following categories; participant characteristics (including depressive symptoms, cognition and informant ratings of cognitive and behavioural change); caregiver characteristics; and the caregiving context. Multivariate analyses were performed to examine the relative contribution of individual variables to burden amongst MCI-caregivers. RESULTS: We found that 36% of MCI-caregivers reported clinically significant levels of burden, twice that of the control informant group. Participant behavioural problems contribute most to burden, with participant depression and possibly cognition also having a significant association. CONCLUSION: Caregiver burden is a considerable problem in MCI and shares some of the same characteristics as caregiver burden in dementia, namely a strong association with challenging behaviours in the patient. This has implications for further research and intervention studies.

Cognitive impairment with and without depression history: an analysis of white matter microstructure.

BACKGROUND: Mild cognitive impairment (MCI) and late-life depression are clinical syndromes that often co-occur and may represent an early manifestation of neurodegenerative disease. The present study examined white matter microstructure in patients with MCI with and without a history of major depression compared with healthy controls. METHODS: Older adults with MCI and no history of major depression (MCI), adults with MCI and euthymic major depression (MCI-MD) and healthy controls underwent comprehensive medical, psychiatric and neuropsychological assessments. Participants also underwent diffusion tensor imaging, which was analyzed using tract-based spatial statistics. White matter hyperintensity (WMH) burden and medical burden were also quantified. RESULTS: We enrolled 30 participants in the MCI group, 36 in the MCI-MD group and 22 in the control group. Compared with controls, participants in the MCI group had significantly reduced fractional anisotropy (FA) in the corpus callosum, superior longitudinal fasciculus (SLF), corona radiata and posterior thalamic radiation. Participants in the MCI-MD group had significantly reduced FA in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiation, sagittal striatum, fornix, SLF, uncinate fasciculus and right cingulum compared with controls. No significant differences in FA were observed between the MCI and MCI-MD groups. Participants in the MCI-MD group had greater medical burden (p = 0.020) and WMH burden than controls (p = 0.013). LIMITATIONS: Study limitations include the cross-sectional design and antidepressant medication use. CONCLUSION: To our knowledge, this study is the first to compare white matter microstructure in patients with MCI with and without a history of major depression and suggests that a common underlying structural white matter change may underpin cognitive impairment in both MCI groups. Further research is needed to delineate the pathophysiological mechanisms underlying these microstructural changes.

The role of glia in late-life depression.

Late-life depression (LLD) has a complex and multifactoral etiology. There is growing interest in elucidating how glia, acting alone or as part of a glial-neuronal network, may contribute to the pathophysiology of depression. In this paper, we explore results from neuroimaging studies showing gray-matter volume loss in key frontal and subcortical structures implicated in LLD, and present the few histological studies that have examined neuronal and glial densities in these regions. Compared to results in younger people with depression, there appear to be age-dependent differences in neuronal pathology but the changes in glial pathology may be more subtle, perhaps reflecting a longer-term compensatory gliosis to earlier damage. We then consider the mechanisms by which both astrocytes and microglia may mediate and modulate neuronal dysfunction and possible degeneration in depression. These include a critical role in the response to peripheral inflammation and central microglial activation, as well as a key role in glutamate metabolism. Advances in our understanding of glia are highlighted, including the role of microglia as "electricians" of the brain and astrocytes as key communicating cells, an integral part of the tripartite synapse. Finally, implications for clinicians are discussed, including the consideration of glia as biomarkers for LLD and incorporation of glia into future therapeutic strategies.

The impact of gender on early ill-health retirement in people with heart disease and depression.

OBJECTIVE: Depression and heart disease are major causes of early ill-health retirement. The effect of comorbid depression on the award of ill-health retirement in those with heart disease is unclear, however, and may differ by gender. Given the deleterious effects of ill-health retirement, identifying at-risk groups is important for guiding targeted interventions. METHOD: We retrospectively analysed baseline data of 20,655 participants from the 45 and Up Study (New South Wales, Australia), who had fully retired between the ages of 45 and 64. We examined the associations of depression and heart disease with ill-health retirement and then adjusted for the presence of common confounders. We then restricted the sample to the 1165 individuals with heart disease prior to retirement, to determine the impact of comorbid depression on IHR and analysed whether there was a differential impact by gender. RESULTS: In the complete sample, 3836 out of 20,655 (18.6%) of the participants retired early due to ill health. Prior heart disease and depression were both independently and strongly associated with ill-health retirement. Those who retired due to ill health were also more likely to be men, less educated, report greater physical disability and were younger at retirement. Among the 1165 for whom heart disease predated any form of retirement, 40% retired due to ill health. Comorbid depression prior to ill-health retirement was strongly associated with an increased risk of this IHR in women (odds ratio = 2.85; 95% confidence interval = 1.20-6.77, p = 0.01), but not in men (interaction term, p = 0.045). CONCLUSIONS: Ill-health retirement is common in those with heart disease. Women appear to be particularly susceptible to the effects of comorbid depression. Given the policy emphasis on reducing the number of people leaving the workforce early, women with early heart disease may represent a particular group in whom interventions designed to detect and treat comorbid depression should be targeted.

Subjective memory complaints, vascular risk factors and psychological distress in the middle-aged: a cross-sectional study.

BACKGROUND: Subjective memory complaints (SMC) are common but their significance is still unclear. It has been suggested they are a precursor of mild cognitive impairment (MCI) or dementia and an early indicator of cognitive decline. Vascular risk factors have an important role in the development of dementia and possibly MCI. We therefore aimed to test the hypothesis that vascular risk factors were associated with SMC, independent of psychological distress, in a middle-aged community-dwelling population. METHODS: A cross-sectional analysis of baseline data from the 45 and Up Study was performed. This is a cohort study of people living in New South Wales (Australia), and we explored the sample of 45, 532 participants aged between 45 and 64 years. SMC were defined as 'fair' or 'poor' on a self-reported five-point Likert scale of memory function. Vascular risk factors of obesity, diabetes, hypertension, hypercholesterolemia and smoking were identified by self-report. Psychological distress was measured by the Kessler Psychological Distress Scale. We tested the model generated from a randomly selected exploratory sample (n = 22, 766) with a confirmatory sample of equal size. RESULTS: 5, 479/45, 532 (12%) of respondents reported SMC. Using multivariate logistic regression, only two vascular risk factors: smoking (OR 1.18; 95% CI = 1.03 - 1.35) and hypercholesterolaemia (OR 1.19; 95% CI = 1.04 - 1.36) showed a small independent association with SMC. In contrast psychological distress was strongly associated with SMC. Those with the highest levels of psychological distress were 7.00 (95% CI = 5.41 - 9.07) times more likely to have SMC than the non-distressed. The confirmatory sample also demonstrated the strong association of SMC with psychological distress rather than vascular risk factors. CONCLUSIONS: In a large sample of middle-aged people without any history of major affective illness or stroke, psychological distress was strongly, and vascular risk factors only weakly, associated with SMC, although we cannot discount psychological distress acting as a mediator in any association between vascular risk factors and SMC. Given this, clinicians should be vigilant regarding the presence of an affective illness when assessing middle-aged patients presenting with memory problems.

Prediction of survival in Alzheimer's disease--the LASER-AD longitudinal study.

OBJECTIVES: Alzheimer's disease (AD) is associated with variable but shortened life expectancy. Knowing expected survival time may empower people with AD and their families, but clinicians currently have limited predictive information. Our objective was to identify determinants of survival in a cohort of people with mild to moderate AD and test these on a separate validation cohort. METHODS: We followed a representative cohort of 158 people for 42 months and identified independent determinants of shorter survival. From these we constructed the Survival in Alzheimer's Model (SAM), and tested this on a validation cohort. RESULTS: Baseline constructional apraxia, age and gait apraxia independently predicted shorter survival: about half of those scoring 2 on the SAM survived > or =3.5 years compared to 85% of those scoring 0. CONCLUSIONS: The SAM is a potentially useful tool for clinicians who previously had very limited specific and quantitative prognostic information to tell AD patients and carers. This model predicted survival from age, constructional and gait apraxia. This may be because constructional and gait apraxia are relatively free from educational or cultural bias and thus are better indicators of severe neuropathology than global cognitive tests. Alternatively, they may increase falls or immobility, or represent disease sub-types with worse prognoses. Oncology services are able to inform patients and their families about 5-year survival rates. This step towards such provision in AD is new and of potential importance to patients and their carers.

Systematic review of the effect of education on survival in Alzheimer's disease.

BACKGROUND: According to the cognitive reserve model, higher levels of education compensate for the neuropathology of Alzheimer's disease (AD), delaying its clinical manifestations. This model suggests that for any level of cognitive impairment, people with more education have worse neuropathology than those with less education and will therefore have shorter survival post-diagnosis. This is the first systematic review of the relationship between more education and decreased survival in people with AD. METHODS: We reviewed the literature systematically, searching electronic databases and reference lists of included studies. We used Centre for Evidence Based Medicine criteria for inclusion and rating of the validity of cohort studies that reported the relationship of education to survival in people with AD. RESULTS: 22 studies met inclusion criteria. We found Grade A evidence (highest evidence level) that more education was not associated with decreased survival post-diagnosis in AD. Only one of 11 studies rated 1b (highest level of quality) supported our hypothesis that more education predicted reduced survival after adjusting for age, gender and dementia severity; it comprised African-Caribbean participants, who had on average more severe cognitive impairment than other studies' participants. CONCLUSIONS: Education delays the onset of the dementia syndrome in AD, but does not lead to earlier death after diagnosis.