First Report®

American Association for Geriatric Psychiatry (AAGP) 2011 Annual Meeting

March 18-21, 2011 San Antonio, TX


Depressive Symptoms Associated With Disrupted Circadian Activity Rhythms in Older Women

San Antonio, TX—Older women with symptoms of depression, even those with mild “subthreshold” levels of depressive symptoms, may also exhibit disrupted circadian rhythms, according to the results of a study presented at the recent AAGP annual meeting. “At this point we can say that if a woman has depressive symptoms, there is a chance she might have disruption of circadian rhythms as well,” said lead author of the study Jeanne E. Maglione, MD, PhD, University of California, San Diego, La Jolla, in an interview with Clinical Geriatrics.

Although it is well recognized that depressive symptoms are common in older adults and that age is associated with changes in circadian rhythms, little is known about the relationship between depressive symptoms and circadian rhythms in older adults. To examine this relationship, Maglione and colleagues conducted a cross-sectional study using data from 3020 community-dwelling older women enrolled in the Study of Osteoporotic Fractures, a larger, ongoing observational cohort study.

All women in this cohort were 70 years of age and older (mean age, 83.55 ± 3.79 years) and were categorized by levels of depressive symptoms based on the Geriatric Depression Scale: 1961 women were categorized as “normal” (score of 0-2); 704 were categorized as “some depressive symptoms” (score of 3-5); and 355 were categorized as “depressed” (score of greater than or equal to 6).

Using wrist actigraphy, the investigators collected circadian activity data on each participant. These data were fitted to a 5-parameter extended cosine model, and activity rhythm variables were computed. These variables included acrophase (defined as time of day of the maximum modeled value for activity), amplitude (difference between maximum and minimum of modeled activity curve), mesor (mean of the modeled rhythm), and pseudo F-statistic (measure of overall fit). Circadian variables were expressed as continuous variables using linear regression; mean circadian activity by depression level was estimated by using the least-squared means procedure.

Circadian variables were also expressed as dichotomous outcomes (acrophase >1.5 standard deviation [SD] above mean vs remainder of sample and >1.5 SD below mean vs remainder of sample; amplitude, mesor, pseudo-F: lowest quartile vs remainder of sample), and logistic regression was used to examine the association between level of depressive symptoms and dichotomous circadian outcome variables.

The study found a significant association between greater level of depressive symptoms and decreased amplitude, mesor, and pseudo F-statistic. For depressive symptoms categorized as “normal,” “some depressive symptoms,” and “depressed,” the mean (95% confidence interval [CI]) amplitude was 1980.92 (1957.68-2004.17), 1885.36 (1845.29-1925.43), and 1898.08 (1838.05-1958.10), respectively (P < .001); the mean (95% CI) mesor was 2498.15 (2473.64-2522.66), 2414.53 (2372.28-2456.78), and 2384.53 (2321.24-2447.81), respectively (P < .001); and the mean (95% CI) pseudo F-statistic was 901.13 (879.48-922.79), 837.77 (800.45-879.09), and 834.39 (778.48-890.30), respectively (P = .005).

The study also found that the greater level of depressive symptoms was significantly associated with increased odds of being in the lowest quartile for amplitude (P < .001), mesor (P < .001), and pseudo F-statistic (P = .005). No association was found between greater level of depressive symptoms and increased odds of acrophase >1.5 SD above or below the mean.

Explaining that the results of this cross-sectional study indicate an association between depressive symptoms and circadian rhythms, Dr. Maglione emphasized that longitudinal studies are needed to explore the relationship further. “We cannot tell if depressive symptoms place women at risk for disrupted circadian rhythms or if disrupted circadian rhythms place women at risk for depression,” she said, adding that future studies should also look at the potential benefit of light exposure in women with disrupted circadian rhythms and depressive symptoms.

Support for this research was provided by the National Institute on Aging.


Caution Encouraged for Use of Antipsychotics to Treat Bipolar Disorder in Older Adults Due to Mortality Risk

San Antonio, TX—Use of atypical antipsychotics to treat older persons with bipolar disorder is associated with an increased mortality risk compared with standard anticonvulsant treatment, indicating the need for caution when prescribing these increasingly used medications in this population, according to the results of a study presented in a poster abstract at the recent AAGP annual meeting.

“Even in nondemented geriatric populations, several commonly used antipsychotics showed an increased risk of mortality compared to standard anticonvulsant treatment when used for primary treatment of bipolar disorder,” said Sachin J. Bhalerao, DO, University of Michigan, Ann Arbor, in an interview with Clinical Geriatrics.

Despite increased concerns in recent years over the use of antipsychotics in older persons, particularly those with dementia, many older patients with bipolar disorder are receiving these medications, as shown in a recent review of national data from Veterans Affairs (VA) that found that nearly 35% of patients older than 60 years with bipolar disorder received antipsychotics as part of their treatment.

To assess the mortality risk associated with the use of the most commonly used antipsychotics compared with the nonantipsychotic drug valproate to treat bipolar disorder in older patients, data were collected on 4854 older patients with bipolar disorder obtained from the national Department of VA registries maintained by the VA Serious Mental Illness Treatment Resource and Evaluation Center at the Ann Arbor VA Medical Center.

Of the 4854 patients, 137 (2.8%) received haloperidol, 868 (17.9%) olanzapine, 1027 (21.2%) risperidone, 1119 (23.0%) quetiapine, and 1703 (35.1%) valproate. All patients in the study were at least 65 years of age, began treatment with one of the studied medications between 2001 and 2008, had a “clean period” of 12 months without any use of antipsychotics or anticonvulsants prior to a new start, and were only taking either the antipsychotic or valproate during the 180-day follow-up. Patients treated with valproate who had a concurrent seizure disorder were not eligible.

Significant differences were noted between the patients treated with haloperidol compared with the other treatment cohorts, including a greater likelihood of being unmarried and African American, higher medical comorbidity, greater use of medical and nursing homes, and less likely to have depression or to be taking antidepressants.

The study found that patients treated with haloperidol had the highest crude mortality rate, with a 180-day mortality rate of 15.3% compared with 2.6% found with quetiapine, which had the lowest mortality rate. Exposure analyses and propensity models adjusted for covariates also showed the highest mortality among patients treated with haloperidol, with a relative risk (RR) (95% confidence interval [CI]) of 1.31 (0.45-3.77) compared with risperidone (reference), olanzapine (RR, 0.75; 95% CI, 0.40-1.43), valproate (RR, 0.42; 95% CI, 0.19-0.96), and quetiapine (RR, 0.28; 95% CI, 0.13-0.62).

“The use of haloperidol, a conventional antipsychotic, showed significantly higher risk of mortality compared to other treatment groups, which is a striking finding and one that is consistent with other recent literature,” said Bhalerao. Emphasizing that antipsychotics are typically used to treat bipolar disorder and are approved by the Food and Drug Administration for such use, Bhalerao said that the results of their study suggest the need for caution in the use of these agents.

“Our message is not to stop using these medicines but for clinicians to consider the mortality risks associated with this group of medications and to use them judiciously,” he said. “In addition, consideration should be given to alternative treatment options such as psychosocial interventions and psychotherapeutic strategies.”


Frailty Is an Important Early-stage Indicator of Quality of Life in Patients With Alzheimer’s Disease

San Antonio, TX—Frailty and neuropsychiatric symptoms in the early stages of Alzheimer’s dementia may be better indicators of quality of life in patients with Alzheimer’s dementia than more commonly used cognitive assessments, researchers noted at the recent AAGP annual meeting.

“We have known for some time the influence of neuropsychiatric symptoms on the quality of life for both dementia patients and their families,” said Aine M. Ni Mhaoláin, MRCPsych, Mercer’s Institute for Research on Ageing, Dublin, Ireland, and lead researcher on the study, in an interview with Clinical Geriatrics. “This is an important area to address in terms of intervention to help support and improve outcomes for our patients and their families.” The finding that frailty at the earlier stages of cognitive impairment could be a factor in quality of life is important because “this may be a new area for intervention given that frailty is suspected to be reversible at its early stages,” said Ni Mhaoláin.

Both frailty and neuropsychiatric symptoms were found to be independent predictors of quality of life for subjects with a Mini-Mental State Examination (MMSE) score of ≥20 in a stepwise linear regression analysis. The sole independent predictor of quality of life in those with an MMSE of ≤20 was functional limitations as measured by the Disability in Dementia score. An MMSE score of ≥20 indicates mild impairment, such that formal assessment may be helpful to better determine pattern and extent of deficits.

The study applied a cross-sectional design of 115 patients with a clinical diagnosis of possible Alzheimer’s dementia. Patients were recruited through the Memory Clinic in St. James’s Hospital, Dublin. The Biological Syndrome Model was used to measure frailty, the 31-question DEMQOL-Proxy measured quality of life, and stepwise regression models were constructed to establish the predictors of quality of life and included measures of illness severity, functional limitations, neuropsychiatric symptoms, and frailty.

Based on the study data, researchers concluded that frailty and behavioral and psychological symptoms are more strongly associated with quality of life than cognition or functional limitation in the earlier stages of Alzheimer’s dementia, an important finding given the potential reversibility of frailty at an early stage. “The surprising aspect of this finding,” said Ni Mhaoláin, “was that frailty had a greater association with quality of life in those with milder cognitive impairment. This suggests to us that there may be a window of opportunity at an early point to address frailty in those with dementia that may influence patient outcomes for the better. This work needs to be validated longitudinally but helps provide direction for future research in the important area of quality of life for dementia patients.”

This study was part-sponsored by an educational grant from Elan Pharmaceuticals (Janssen acquired the Alzheimer Immunotherapy Program from Elan Pharmaceuticals in September 2009) and Wyeth (which was acquired by Pfizer in October 2009). The financial sponsor was not involved in the design, collection, or interpretation of data involved in this study.