Keri Diamond

Enhancing Memory in Late-Life Depression: The Effects of a Combined Psychoeducation and Cognitive Training Program

OBJECTIVE To evaluate the efficacy of a multifactorial cognitive training (CT) program for older people with a lifetime history of depressive disorder. METHODS This was a single-blinded waitlist control design. The study was conducted in the Healthy Brain Ageing Clinic, a specialist outpatient clinic at the Brain & Mind Research Institute, Sydney, Australia. Forty-one participants (mean age = 64.8 years, sd = 8.5) with a lifetime history of major depression were included. They were stabilized on medication and had depressive symptoms in the normal to mild range. The intervention encompassed both psychoeducation and CT. Each component was 1-hour in duration and was delivered in a group format over a 10-week period. Psychoeducation was multifactorial, was delivered by health professionals and targeted cognitive strategies, as well depression, anxiety, sleep, vascular risk factors, diet and exercise. CT was computer-based and was conducted by Clinical Neuropsychologists. Baseline and follow-up neuropsychological assessments were conducted by Psychologists who were blinded to group allocation. The primary outcome was memory whilst secondary outcomes included other aspects of cognition and disability. RESULTS CT was associated with significant improvements in visual and verbal memory corresponding to medium to large effect sizes. CONCLUSION CT may be a viable secondary prevention technique for late-life depression, a group who are at risk of further cognitive decline and progression to dementia.

Glutathione relates to neuropsychological functioning in mild cognitive impairment

Mild cognitive impairment (MCI) represents an at‐risk state for Alzheimers disease in which underlying pathophysiological mechanisms could be delineated. Oxidative stress has been implicated in Alzheimers disease and can be measured by levels of the antioxidant glutathione. This study aims to assess in vivo levels of glutathione via proton magnetic resonance spectroscopy in patients with MCI and to determine how glutathione relates to cognitive decline.

Sleep disturbance relates to neuropsychological functioning in late-life depression

BACKGROUND Sleep-wake disturbance in older people is a risk factor for depression onset and recurrence. The aim of this study was to determine if objective sleep-wake disturbance in late-life depression relates to neuropsychological functioning. METHODS Forty-four older patients with a lifetime history of major depression and 22 control participants underwent psychiatric, medical and neuropsychological assessments. Participants completed self-report sleep measures, sleep diaries and wore wrist actigraphy for two weeks. Outcome measures included sleep latency, the number and duration of nocturnal awakenings and the overall sleep efficiency. RESULTS Patients with depression had a greater duration of nocturnal awakenings and poorer sleep efficiency, in comparison to control participants. Sleep disturbance in patients was associated with greater depression severity and later ages of depression onset. It also related to poorer psychomotor speed, poorer verbal and visual learning, poorer semantic fluency as well as poorer performance on tests of executive functioning. These relationships largely remained significant after controlling for depression and estimated apnoea severity. LIMITATIONS This sample had only mild levels of depression severity and results require replication in patients with moderate to severe depression. The inclusion of polysomnography and circadian markers would be useful to delineate the specific features of sleep-wake disturbance that are critical to cognitive performance. CONCLUSIONS Sleep-wake disturbance in older patients with depression is related to neuropsychological functioning and to later ages of illness onset. This study suggests that common neurobiological changes may underpin these disease features, which may, in turn, warrant early identification and management.

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.

Accelerated long-term forgetting of verbal information in unilateral temporal lobe epilepsy: Is it related to structural hippocampal abnormalities and/or incomplete learning?

The factors contributing to accelerated long-term forgetting (ALF) are not yet clear. In this study, a 12-item word list was presented repeatedly to 23 patients with temporal lobe epilepsy (TLE) and 27 control participants (NC) until it was recalled completely on two consecutive trials or until 12 trials were undertaken. Compared to NCs, patients with hippocampal lesions and those who failed to learn the list showed ALF by one day post learning, but the alternative patient groups also showed ALF when tested after seven days. Overall, our findings suggest that in patients with TLE neither a preserved hippocampus nor intact learning protects against ALF.

Using informant reports to detect cognitive decline in mild cognitive impairment.

BACKGROUND The use of informant rating scales in older adults at risk of dementia may assist with early detection and intervention strategies. This study aims to evaluate whether informants rate greater cognitive change in patients with mild cognitive impairment (MCI) compared to cognitively intact individuals, and to determine the relationship between informant ratings of cognitive change and neuropsychological performance. METHODS One hundred and nine health-seeking older adults underwent clinical and neuropsychological assessments, and informants completed the Cambridge Behavioral Inventory-Revised (CBI-R). Patients were rated according to MCI criteria, including amnestic and non-amnestic subtypes, or as being cognitively intact. CBI-R ratings were evaluated with respect to MCI diagnosis and neuropsychological performance. RESULTS Compared to cognitively intact individuals, informants rated patients with MCI as having significantly more change in overall functioning (p < 0.05) as well as in specific domains of memory and orientation (p < 0.01), everyday skills (p < 0.05), and motivation (p < 0.05), even after controlling for depressive symptom severity. In further analyses, the non-amnestic MCI subgroup only had more informant-rated mood changes compared to the amnestic subgroup. In relation to neuropsychological performance, informant ratings were related to poorer visual memory, verbal learning and memory, language, and psychomotor speed, with correlations ranging from -0.19 to -0.43 (p < 0.05). CONCLUSIONS These findings indicate that informants are sensitive to subtle early cognitive change in individuals with MCI, and that their ratings are related to objectively measured neuropsychological performance. Thus, the CBI-R may be valuable in assisting early screening and intervention processes.

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.

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.