Matthew Paradise

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.

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

Alzheimers 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.

Mild Cognitive Impairment Subtypes in Older People With Depressive Symptoms Relationship With Clinical Variables and Hippocampal Change

Aims: To examine the rates and clinical characteristics of mild cognitive impairment (MCI) in older people with depressive symptoms and to determine the relative contribution of hippocampal volume and MCI to memory change. Method: One hundred and fifty-two participants with lifetime Major Depression and remitted or mild symptoms and 28 healthy controls underwent psychiatric and neuropsychological assessments. Magnetic resonance imaging was also conducted in a subset of the patients (n = 81) and healthy controls (n = 18). Results: MCI was diagnosed in 75.7% of the patients and was associated with increasing age, medical burden, vascular risk factors, later age of depression onset and smaller hippocampi. Multiple regression showed that both hippocampal volume and MCI diagnosis mediate memory performance in depression. Conclusions: MCI occurs in older adults with a history of depression and is not simply due to symptom severity. Memory change is linked to underlying hippocampal atrophy in this patient group.

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.

Clinical and Cognitive Correlates of Structural Hippocampal Change in "At-Risk" Older Adults

With estimates of dementia expected to rise over the coming decades, there is interest in understanding the factors associated with promoting neuroprotection and limiting neurodegeneration. In this study, we examined the change in the volume of the hippocampus over a 2-month period in 34 older people “at risk” of cognitive decline (mean age = 66.8 years, 38% male). Factors that were examined included cognitive reserve, neuropsychological functioning, depression as well as a lifestyle (cognitive training) intervention. The results showed that over a 2-month period, increases in hippocampal size were associated with having higher premorbid intellect, greater occupational attainment, superior memory, and higher levels of functioning. Conversely, depression and disability were associated with decreases in hippocampal volume. Cognitive training was not associated with changes in hippocampal volume. These findings suggest that factors associated with cognitive reserve, cognition and depression may play an integral pathophysiological role in determining hippocampal volumes in “at-risk” older adults.

Neuroimaging and neuropathology indices of cerebrovascular disease burden: A systematic review

Objective To systematically review the literature on the use of both neuroimaging and neuropathologic indices of cerebrovascular disease (CVD) burden, as estimation of this burden could have multiple benefits in the diagnosis and prognosis of cognitive impairment and dementia. Methods MEDLINE and EMBASE databases were searched (inception to June 2017) to obtain and then systematically review all pertinent neuroimaging and neuropathology studies, where an index of CVD was developed or tested. Results Twenty-five neuroimaging articles were obtained, which included 4 unique indices. These utilized a limited range of CVD markers from mainly structural MRI, most commonly white matter hyperintensities (WMH), cerebral microbleeds, and dilated perivascular spaces. Weighting of the constituent markers was often coarse. There were 7 unique neuropathology indices, which were heterogeneous in their regions sampled and lesions examined. Conclusion There is increasing interest in indices of total CVD burden that incorporate multiple lesions, as traditional individual markers of CVD such as WMH only provide limited information. Neuropathologic indices are needed to validate neuroimaging findings. The studies clearly demonstrated proof of concept that information from multiple imaging measures of CVD provide more information, including a stronger association with cognitive impairment and dementia, than that provided by a single measure. There has been limited exploration of the psychometric properties of published indices and no comparison between indices. Further development of indices is recommended, including the use of data from diffusion tensor and perfusion imaging.

The association of regional white matter lesions with cognition in a community-based cohort of older individuals

Emerging evidence from lesion-symptom mapping (LSM) studies suggested that regional white matter lesions (WML) on strategic white matter (WM) fiber tracts are significantly associated with specific cognitive domains, independent of global WML burden. However, previous LSM investigations were mostly carried out in disease cohorts, with little evidence from community-based older individuals, making findings difficult to generalize. Moreover, most LSM studies applied a threshold to the probabilistic atlas, leading to the loss of information and threshold-dependent findings. Furthermore, it is still unclear whether associations between regional WML and cognition are independent of global grey matter (GM) and WM volumes, which have also been linked to cognition. In the current study, we undertook a region of interest (ROI) LSM study to examine the relationship between regional WML on strategic WM tracts and cognitive performance in a large community-based cohort of older individuals (N = 461; 70–90 years). WML were extracted using a publicly available pipeline, UBO Detector (https://cheba.unsw.edu.au/group/neuroimaging-pipeline). Mapping of WML to the Johns Hopkins University WM atlas was undertaken using an automated TOolbox for Probabilistic MApping of Lesions (TOPMAL), which we introduce here, and is implemented in UBO Detector. The results show that different patterns of brain structural volumes in the ageing brain were associated with different cognitive domains. Regional WML were associated with processing speed, executive function, and global cognition, independent of total GM, WM and WML volumes. Moreover, regional WML explained more variance in executive function, compared to total GM, WM and WML volumes. The current study highlights the importance of studying regional WML in age-related cognitive decline.