Akshya Vasudev

Vascular Burden Predicts Gait, Mood, and Executive Function Disturbances in Older Adults with Mild Cognitive Impairment: Results from the Gait and Brain Study

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White matter changes in late-life depression: A diffusion tensor imaging study

BACKGROUND Numerous studies have revealed white matter abnormalities in late-life depression (LLD). The objective was to investigate the integrity of white matter tracts in subjects with LLD compared to similar aged healthy individuals using diffusion tensor imaging (DTI). METHODS Sixty eight subjects (30 healthy individuals, 38 depressed) underwent DTI on a 3T scanner following clinical and cognitive assessment. An automated tract-based spatial statistics (TBSS) method was used to derive estimates of fractional anisotropy (FA) and mean diffusivity (MD) for each subject. Group effects and correlations with clinical features on DTI parameters were examined. RESULTS Compared to controls, uncorrected maps revealed patients with LLD exhibited lower FA in frontal, temporal and midbrain regions relative to older healthy subjects (p<0.05). However, using corrected maps no significant differences were observed in LLD patients in FA and MD parameters (p<0.05, family-wise error corrected for multiple comparisons). Regression analyses revealed no significant relationship between DTI parameters and current depressive symptoms in LLD (p>0.05, uncorrected and corrected). CONCLUSIONS Findings are suggestive of loss of integrity in white matter fibres within frontal, temporal and midbrain regions, increasing the evidence that implicates disruptions to the limbic-orbitofrontal networks in the pathogenesis of LLD. However, as results did not survive strict control for multiple comparisons, they should be considered tentative and replication in larger cohorts is needed.

Trends in Psychotropic Dispensing Among Older Adults with Dementia Living in Long-Term Care Facilities: 2004-2013.

OBJECTIVE Guidelines worldwide have cautioned against the use of antipsychotics as first-line agents to treat neuropsychiatric symptoms of dementia. We aimed to investigate the changes over time in the dispensing of antipsychotics and other psychotropics among older adults with dementia living in long-term care facilities. METHODS We used drug claims data from Ontario, Canada, to calculate quarterly rates of prescription dispensing of six psychotropic drug classes among all elderly (≥65 years of age) long-term care residents with dementia from January 1, 2004, to March 31, 2013. Psychotropic drugs were classified into the following categories: atypical and conventional antipsychotics, non-sedative and sedative antidepressants, anti-epileptics, and benzodiazepines. We used time-series analysis to assess trends over time. RESULTS The study sample increased by 21% over the 10-year study period, from 49,251 patients to 59,785 patients. The majority of patients (within the range of 75%-79%) were dispensed at least one psychotropic medication. At the beginning of the study period atypical antipsychotics (38%) were the most frequently dispensed psychotropic, followed by benzodiazepines (28%), non-sedative antidepressants (27%), sedative antidepressants (17%), anti-epileptics (7%), and conventional antipsychotics (3%). Dispensing of anti-epileptics (2% increase) and conventional antipsychotics (1% decrease) displayed modest changes over time, but we observed more pronounced changes in dispensing of benzodiazepines (11% decrease) and atypical antipsychotics (4% decrease). Concurrently, we observed a substantial growth in the dispensing of both sedative (15% increase) and non-sedative (9% increase) antidepressants. The proportion of patients dispensed two or more psychotropic drug classes increased from 42% in 2004 to 50% in 2013. CONCLUSIONS Utilization patterns of psychotropic drugs in institutionalized patients with dementia have changed over the past decade. Although their use declined slightly over the study period, atypical antipsychotics continue to be used at a high rate. A decline in the use of benzodiazepines along with an increased use of sedative and non-sedative antidepressants suggests that the latter class of drugs is being substituted for the former in the management of neuropsychiatric symptoms. Psychotropic polypharmacy continues to be highly prevalent in these patient samples.

'Bipolar disorder' in the elderly: what's in a name?

Bipolar disorder is a chronic disorder of mood which leads to episodes of either elevated mood or depression in a sizable number of adults in the community (1%). Though the prevalence rates in the elderly are lower in the community (up to 0.1%), there is significantly higher morbidity in protected environments like care homes and hospital settings where prevalence rates may be as high as 10%. Bipolar disorder in the elderly is probably heterogenous and its etiopathogenesis is complex. Bipolar disorder may be divided into two distinct subtypes, the late onset bipolar (LOB) and the early onset bipolar (EOB) groups. LOB patients tend to have a milder illness in terms of manic severity but they have higher medical and neurological burden. They also have lower familial burden of bipolar illness as compared to EOB patients. There is an increased risk of dementia and stroke in patients with late life bipolar disorder (and there may be a protective effect of lithium in preventing dementia). White matter changes, as seen by increased white matter hyperintensities on neuroimaging, are also increased, providing further evidence of cerebrovascular disease. Treatment of late life bipolar is currently based on guidelines drawn up for younger bipolar disorder patients. Good quality intervention studies are needed to estimate the possible protective effect of cognitive enhancers and/or vascular prevention strategies. This review suggests that late life bipolar disorder, particularly late onset bipolar disorder, is probably a distinct diagnostic entity compared to the younger bipolar patients as it has a different presentation, etiology and hence perhaps needs different treatment strategies.

A study of orthostatic hypotension, heart rate variability and baroreflex sensitivity in late-life depression.

BACKGROUND To determine if subjects with late-life depression have significant cardiovascular autonomic abnormalities (orthostatic blood pressure drop, heart rate variability and baroreflex sensitivity). METHODS A case-control study, in secondary care facilities, of forty two older (> 60 years) individuals with lifetime history of major depression and 31 age and sex matched comparison subjects. Autonomic function was assessed by measuring postural blood pressure, heart rate variability and baroreflex sensitivity using non-invasive beat-to-beat blood pressure and continuous ECG monitoring (Task Force® Monitor, CNSystems, Graz, Austria). The main outcome measures were maximal reduction in systolic blood pressure with active stand, low frequency and high frequency heart rate variability and baroreflex sensitivity using the sequence method. RESULTS Participants with depression had a significantly larger drop in systolic blood pressure on standing from a supine position. Depression was an independent predictor for developing systolic orthostatic hypotension. Depressed participants also had lower low frequency heart rate variability and lower baroreflex sensitivity. LIMITATIONS This was a cross-sectional and observational study; longitudinal effects or causality cannot be inferred from the findings and we could not distinguish state from trait related changes. CONCLUSIONS Late-life depression has been associated with vascular disease but previous studies examining vascular risk factors have been inconsistent. Brain MRI white matter hyperintensities are ischemic and increased in late-life depression and associated with orthostatic blood pressure drops in animals. The presence of autonomic abnormalities in late-life depression may partly explain these inconsistencies and be associated with the development of brain white matter hyperintensities.

Relationship between cognition, magnetic resonance white matter hyperintensities, and cardiovascular autonomic changes in late-life depression.

OBJECTIVES To explore the relationship between specific aspects of cognition, white matter hyperintensities (WMHs), and cardiovascular autonomic parameters in late-life depression (LLD). DESIGN Cross-sectional analysis. SETTING Secondary care psychiatry. PARTICIPANTS Forty-one individuals older than 60 years, with current or previous history of major depression, and 32 age-matched comparison subjects. MEASUREMENTS Cognition was assessed by a standardized computer battery of tasks (Cognitive Drug Research) that measured processing speed, attention, episodic memory, and working memory. Cardiovascular autonomic parameters were estimated by a noninvasive device that calculated blood pressure, heart rate variability, and baroreflex sensitivity (Task Force Monitor). Magnetic resonance imaging was performed on a 3-T magnetic resonance imaging system, and WMH volume was estimated using an automated validated method. RESULTS As expected, cognitive deficits in all tested domains were present in LLD subjects compared with comparison subjects. In the LLD group, processing speed was correlated with scores on memory and working memory tasks. Attentional deficits were correlated with total and periventricular WMH volume, and episodic memory was associated with heart rate variability. There were no associations between cognitive variables and traditional vascular risk factors or between cognitive variables and any of these parameters in the comparison subjects. CONCLUSIONS This study suggests that processing speed may be an important factor underlying deficits in LLD, but it also indicates that other factors, including those related to vascular disease, are important and thus provide further support for the vascular depression hypothesis.

Music therapy in patients with dementia and behavioral disturbance on an inpatient psychiatry unit: results from a pilot randomized controlled study.

The prevalence of dementia continues to grow worldwide due to an aging population and is projected to affect 65.7 million people by 2030 (World Health Organization, 2012). Behavioral and psychological symptoms of dementia (BPSD), including agitation, anxiety, aggression, depression, and psychosis, can occur in as much as 80% of the affected population, frequently necessitating psychiatric admission. Traditionally BPSD have been treated using pharmacological approaches. However, such medications could have serious adverse effects and additionally have limited efficacy in reducing such symptoms (Ballard et al., 2009).

Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

Background The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. Methods We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Results Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Conclusion Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

Association between Antidepressants and Fall-Related Injuries among Long-Term Care Residents

OBJECTIVES Antidepressants are associated with an increased risk of falls although little is known of the comparative risks of different types of antidepressants or individuals who are at greatest risk for falls. We examined the association between new use of antidepressants and fall-related injuries among older adults in long-term care (LTC). DESIGN, SETTING, PARTICIPANTS This was a matched, retrospective cohort study involving LTC residents in Ontario, Canada, from 2008 to 2014. New users of antidepressants were matched to non-users of antidepressants. MEASUREMENTS The primary outcome was any fall resulting in an emergency department (ED) visit or hospitalization within 90 days after exposure. Secondary outcomes included hip fractures, wrist fractures, and falls reported in LTC. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval associated with antidepressants and outcomes. RESULTS New users of any antidepressant had an increased risk of ED visits or hospitalization for falls within 90 days when compared with individuals not receiving antidepressants (5.2% versus 2.8%; adjusted OR: 1.9, 95% CI: 1.7-2.2). Antidepressants were also associated with an increased risk of all secondary outcomes. The increased risk of fall-related injuries was evident among selective-serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, trazodone, and across multiple patient subgroups. CONCLUSIONS New use of antidepressants is associated with significantly increased risk of falls and fall-related injuries among LTC residents across different patient subgroups and antidepressant classes. The potential risk of fall-related outcomes should be carefully considered when initiating antidepressants among older adults in LTC.

A training programme involving automatic self-transcending meditation in late-life depression: preliminary analysis of an ongoing randomised controlled trial

Late-life depression affects 2–6% of seniors aged 60 years and above. Patients are increasingly embracing non-pharmacological therapies, many of which have not been scientifically evaluated. This study aimed to evaluate a category of meditation, automatic self-transcending meditation (ASTM), in alleviating symptoms of depression when augmenting treatment as usual (NCT02149810). The preliminary results of an ongoing single-blind randomised controlled trial comparing a training programme involving ASTM with a wait-list control indicate that a 12-week ASTM programme may lead to significantly greater reductions in depression and anxiety severity. As such, ASTM may be an effective adjunctive therapy in the treatment of late-life depression. Declaration of interest R.I.N. is Director of Research and Health Promotion for the Art of Living Foundation, Canada and supervised the staff providing ASTM training. Copyright and usage