- Email: [email protected]
The Relationships Between Vascular Risk, Cognition and Outcome in Late-Life Psychotic Depression
2015 AAGP Annual Meeting difficulties, and baseline depression scores. We assessed risk of discharge to hospital (according to Medicare hospitalization claims) in the 30-day and 60-day periods following start of care. Results: Of 755 total eligible patients, 195 (25.8%) patients were hospitalized during the 60-day study period. At 30 days from start of care, 68 (15.5%) CAREPATH patients and 69 (22.0%) usual care patients were hospitalized. The 30-day risk of hospitalization among CAREPATH patients was approximately 30% lower compared to usual care (adjusted Relative Risk (RR) ¼ 0.70, p¼.020). At 60 days from start of care, 103 (23.5%) CAREPATH patients were hospitalized and 92 (29.4%) usual care patients were hospitalized. The 60-day risk of hospitalization remained approximately 20% lower among CAREPATH patients (RR¼0.79, p¼.055). Using cox proportional hazards models to account for individual differences in time at-risk, the risk of hospitalization was approximately 34% lower (adjusted Hazard Ratio (HR) ¼ 0.66, p¼.015) among CAREPATH patients after 30 days, and approximately 29% lower (HR ¼ 0.71, p¼.019) after 60 days. Conclusions: Patients receiving CAREPATH depression care were significantly less likely to experience acute care hospitalization during 30-day and 60-day Medicare home health episodes. Results suggest that depression care management may be an important element of routine home health and post-acute care practices, not only to treat depression but to reduce risk of adverse outcomes and associated medical costs.
Poster Number: EI 36
The Relationships Between Vascular Risk, Cognition and Outcome in Late-Life Psychotic Depression Kathleen Bingham, MD1; Ellen Whyte, MD2; Barnett S. Meyers, MD3; Benoit H. Mulsant, MD1,4; Anthony J. Rothschild, MD5; Samprit Banerjee, PhD, MStat3; Alastair J. Flint, MD1,6 1
Department of Psychiatry, University of Toronto, Toronto, ON, Canada Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 3 Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 4 Centre for Addiction and Mental Health, Toronto, ON, Canada 5 University of Massachusetts Medical School and University of Massachusetts, Worcester, MA 6 University Health Network, Toronto, ON, Canada 2
Introduction: There is a complex relationship between late-life depression (LLD), cerebrovascular disease (CVD) and cognition. The “depression executive dysfunction syndrome” describes a subgroup of patients with LLD and executive dysfunction, along with other signs of frontostriatal impairment. A limited number of studies have found that executive dysfunction in LLD predicts poorer treatment outcome, although other research has not found this to be the case. Some authors have proposed that processing speed, not executive dysfunction, is the core cognitive deficit in LLD and may be more predictive of outcome. Clinical and neuroimaging data suggest CVD as an etiology of frontostriatal impairment, via ischemic damage to white matter tracts. However, there is mixed evidence directly linking vascular disease, itself, to the onset and outcome of LLD. As a large, well-characterized sample, the Study of Pharmacotherapy of Psychotic Depression (STOP-PD) data set provides an excellent opportunity to investigate the relationship between vascular risk, cognitive dysfunction and depression outcome in nondemented older persons with major depression. The aim of this study was to determine whether vascular risk, executive function and/or processing speed are associated with poorer treatment outcome in late-life psychotic depression. Furthermore, if both vascular risk and cognitive function are predictive of outcome, we wished to examine whether vascular risk mediated the association between cognition and outcome. Our hypotheses were as follows: 1. Worse baseline executive function and processing speed would each be independently associated with poorer treatment outcome. 2. Greater baseline vascular risk would be independently associated with poorer treatment outcome. 3. Vascular risk would mediate the association between executive function and/or processing speed and treatment outcome. Methods: This study is a secondary analysis of data from STOP-PD, a four-site, 12-week randomized controlled trial comparing olanzapine plus sertraline with olanzapine plus placebo in the acute treatment of persons aged 18 years or older with psychotic depression. We analyzed data pertaining to the group of participants aged 60 years (n¼142). The independent variables were baseline vascular risk (defined using the Framingham Stroke Risk Score), baseline executive function (colour-word interference score on the Stroop) and baseline processing speed (each of the timed colour and word reading components of the Stroop). Our primary outcome measure was change in depression severity across treatment groups, measured with the 17-item HAM-D total score at each visit during the 12-week treatment trial. The data were analyzed with mixed-effects models examining the relation of each of the predictor variables with outcome. Each model included the following selected covariates known to affect depression outcome and/or cognitive performance: age, gender, level of education, age at onset of major depressive disorder, duration of index depressive episode, treatment resistance during the index depressive episode, and cumulative medical burden. Results: Baseline vascular risk was independently and significantly associated with change in HAM-D score (F1,791 ¼ 9.91, p ¼ 0.0017): the greater the baseline vascular risk, the less improvement in depression severity over time. Neither executive function
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2015 AAGP Annual Meeting nor processing speed was a significant predictor of depression outcome. Because we did not find a relationship between cognitive measures and outcome, we were not able to test the mediator hypothesis. Conclusions: Our results support the hypothesis that vascular disease is associated with poorer treatment outcome of LLD. Vascular risk, as determined by Framingham score, has been found to be correlated with severity of white matter changes on brain MRI in LLD. Our findings confirm the utility of the Framingham Stroke Risk Score as a simple clinical measure in predicting poorer treatment response in LLD. We did not find that measures of executive function or processing speed independently predicted treatment outcome in this group of older patients with psychotic depression: possible reasons for this finding will be discussed. This research was funded by: The STOP-PD study, on which This research is based, was funded by USPHS grants MH 62446, MH 62518, MH 62565, and MH 62624 from the National Institute of Mental Health.
Poster Number: EI 37
Olfactory Identification Deficit as a Predictor of White Matter Tract Integrity in Alzheimer’s Disease
Matthew R. Woodward, MSc, OMS-II1; Michael G. Dwyer, PhD3; Chaitanya V. Amrutkar, MD2; Robert Zivadinov, MD, PhD3; Kinga Szigeti, MD, PhD2 1
Touro College of Osteopathic Medicine, New York, NY Alzheimer’s Disease and Memory Disorders Center, Department of Neurology, University at Buffalo, SUNY, Buffalo, NY 3 Buffalo Neuroimaging Analysis Center, University at Buffalo, SUNY, Buffalow, NY 2
Introduction: While Alzheimer’s disease (AD) is characteristically a disease of gray matter atrophy, particularly cortical and hippocampal, studies have demonstrated a loss of white matter function as well. Diffusion Tensor Imaging (DTI) provides a sensitive in vivo predictor of white matter tract integrity by measuring fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (l1), and radial diffusivity (RD). Studies have suggested that MD and l1 might represent a ‘state-specific’ marker for Alzheimer’s pathology whereas FA and RD may function as markers for disease progression. Olfactory dysfunction is common in cognitive impairment and has demonstrated potential utility as a non-invasive screening tool. A 10-item subset of the University of Pennsylvania Smell Identification Test (UPSIT) has been proposed as a screening tool for mild cognitive impairment (MCI) and AD. Decreased white matter tract integrity of the olfactory tract was reported in MCI. There was a positive correlation between UPSIT score and FA of the superior longitudinal fasciculus (SLF). A negative correlation between UPSIT and MD of the SLF was reported. We correlated olfactory identification deficits with white matter tract integrity within the context of amnestic disorders to: (1) assess whether amnestic disorders (aMCI or AD) are associated with disturbances in white matter tract integrity and (2) assess whether olfactory identification deficits are associated with greater white matter tract impairment within groups. Methods: Cross sectional structural analysis of 3T MRI with a 25-direction DTI sequence of 66 subjects (26 AD, 15 MCI, 25 HC) was performed. Diagnosis, age and ApoE genotype were added to the models as appropriate. Smellers were defined as >¼7 correct answers on the 10 item subset of the University of Pennsylvania Smell Identification Test (UPSIT) and non-smellers as <7 correct answers. The cutoff of 7 was selected based on the ROC/AUC to optimize sensitivity and specificity. Imaging data were processed and analyzed using FSL 5.0. Subject level means for FA, MD, l1 and RD were calculated from white matter skeletons. As a post hoc analysis, subject level means for FA, MD, l1 and RD were also calculated from the olfactory tract ROI skeleton. A voxel-based analysis of white matter tract integrity was conducted using TBSS. Results: There was a significant decrease of FA on subject level means of DTI skeletons in AD patients with respect to HC (p¼ 0.037). Furthermore, MD, l1 and RD were all significantly increased in both MCI (P¼0.002, 0.001, 0.005, respectively) and AD (p<0.0001 for MD, l1, RD) compared with HC. There were no statistically significant differences between MCI and AD. With respect to subject level means within the ROI skeleton of the olfactory tract, impairment in olfactory identification were associated with decreased FA in olfactory identification deficits (p¼0.007) and increased RD (p¼0.048). There were trends toward statistical significance with respect to both MD and l1 (p¼0.052, 0.07, respectively). TBSS analyses have demonstrated widespread statistically significant difference in MD between ‘smellers’ and ‘non-smellers’ within the Alzheimer’s group. Conclusions: These findings suggest that there is a loss of white matter tract integrity in both MCI and AD, with respect to healthy controls, with no statistically significant differences between the two amnestic disorders detected in this study. The lack of statistical difference between MCI and AD may be a result of limited statistical power. White matter tract integrity in the olfactory tract of subjects with olfactory identification deficits within the AD group was lost, supporting olfactory system neurodegeneration. These findings suggest that white matter tract impairment is present in amnestic disorders, and these changes may occur prior to clinical progression to AD. Markers for decreased white matter tract integrity within the olfactory tract provides a potential neuroanatomical correlate to the olfactory impairment commonly reported in amnestic disorders.
Am J Geriatr Psychiatry 23:3, Supplement 1
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Poster Number: EI 36
The Relationships Between Vascular Risk, Cognition and Outcome in Late-Life Psychotic Depression Kathleen Bingham, MD1; Ellen Whyte, MD2; Barnett S. Meyers, MD3; Benoit H. Mulsant, MD1,4; Anthony J. Rothschild, MD5; Samprit Banerjee, PhD, MStat3; Alastair J. Flint, MD1,6 1
Department of Psychiatry, University of Toronto, Toronto, ON, Canada Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 3 Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 4 Centre for Addiction and Mental Health, Toronto, ON, Canada 5 University of Massachusetts Medical School and University of Massachusetts, Worcester, MA 6 University Health Network, Toronto, ON, Canada 2
Introduction: There is a complex relationship between late-life depression (LLD), cerebrovascular disease (CVD) and cognition. The “depression executive dysfunction syndrome” describes a subgroup of patients with LLD and executive dysfunction, along with other signs of frontostriatal impairment. A limited number of studies have found that executive dysfunction in LLD predicts poorer treatment outcome, although other research has not found this to be the case. Some authors have proposed that processing speed, not executive dysfunction, is the core cognitive deficit in LLD and may be more predictive of outcome. Clinical and neuroimaging data suggest CVD as an etiology of frontostriatal impairment, via ischemic damage to white matter tracts. However, there is mixed evidence directly linking vascular disease, itself, to the onset and outcome of LLD. As a large, well-characterized sample, the Study of Pharmacotherapy of Psychotic Depression (STOP-PD) data set provides an excellent opportunity to investigate the relationship between vascular risk, cognitive dysfunction and depression outcome in nondemented older persons with major depression. The aim of this study was to determine whether vascular risk, executive function and/or processing speed are associated with poorer treatment outcome in late-life psychotic depression. Furthermore, if both vascular risk and cognitive function are predictive of outcome, we wished to examine whether vascular risk mediated the association between cognition and outcome. Our hypotheses were as follows: 1. Worse baseline executive function and processing speed would each be independently associated with poorer treatment outcome. 2. Greater baseline vascular risk would be independently associated with poorer treatment outcome. 3. Vascular risk would mediate the association between executive function and/or processing speed and treatment outcome. Methods: This study is a secondary analysis of data from STOP-PD, a four-site, 12-week randomized controlled trial comparing olanzapine plus sertraline with olanzapine plus placebo in the acute treatment of persons aged 18 years or older with psychotic depression. We analyzed data pertaining to the group of participants aged 60 years (n¼142). The independent variables were baseline vascular risk (defined using the Framingham Stroke Risk Score), baseline executive function (colour-word interference score on the Stroop) and baseline processing speed (each of the timed colour and word reading components of the Stroop). Our primary outcome measure was change in depression severity across treatment groups, measured with the 17-item HAM-D total score at each visit during the 12-week treatment trial. The data were analyzed with mixed-effects models examining the relation of each of the predictor variables with outcome. Each model included the following selected covariates known to affect depression outcome and/or cognitive performance: age, gender, level of education, age at onset of major depressive disorder, duration of index depressive episode, treatment resistance during the index depressive episode, and cumulative medical burden. Results: Baseline vascular risk was independently and significantly associated with change in HAM-D score (F1,791 ¼ 9.91, p ¼ 0.0017): the greater the baseline vascular risk, the less improvement in depression severity over time. Neither executive function
S102
Am J Geriatr Psychiatry 23:3, Supplement 1
2015 AAGP Annual Meeting nor processing speed was a significant predictor of depression outcome. Because we did not find a relationship between cognitive measures and outcome, we were not able to test the mediator hypothesis. Conclusions: Our results support the hypothesis that vascular disease is associated with poorer treatment outcome of LLD. Vascular risk, as determined by Framingham score, has been found to be correlated with severity of white matter changes on brain MRI in LLD. Our findings confirm the utility of the Framingham Stroke Risk Score as a simple clinical measure in predicting poorer treatment response in LLD. We did not find that measures of executive function or processing speed independently predicted treatment outcome in this group of older patients with psychotic depression: possible reasons for this finding will be discussed. This research was funded by: The STOP-PD study, on which This research is based, was funded by USPHS grants MH 62446, MH 62518, MH 62565, and MH 62624 from the National Institute of Mental Health.
Poster Number: EI 37
Olfactory Identification Deficit as a Predictor of White Matter Tract Integrity in Alzheimer’s Disease
Matthew R. Woodward, MSc, OMS-II1; Michael G. Dwyer, PhD3; Chaitanya V. Amrutkar, MD2; Robert Zivadinov, MD, PhD3; Kinga Szigeti, MD, PhD2 1
Touro College of Osteopathic Medicine, New York, NY Alzheimer’s Disease and Memory Disorders Center, Department of Neurology, University at Buffalo, SUNY, Buffalo, NY 3 Buffalo Neuroimaging Analysis Center, University at Buffalo, SUNY, Buffalow, NY 2
Introduction: While Alzheimer’s disease (AD) is characteristically a disease of gray matter atrophy, particularly cortical and hippocampal, studies have demonstrated a loss of white matter function as well. Diffusion Tensor Imaging (DTI) provides a sensitive in vivo predictor of white matter tract integrity by measuring fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (l1), and radial diffusivity (RD). Studies have suggested that MD and l1 might represent a ‘state-specific’ marker for Alzheimer’s pathology whereas FA and RD may function as markers for disease progression. Olfactory dysfunction is common in cognitive impairment and has demonstrated potential utility as a non-invasive screening tool. A 10-item subset of the University of Pennsylvania Smell Identification Test (UPSIT) has been proposed as a screening tool for mild cognitive impairment (MCI) and AD. Decreased white matter tract integrity of the olfactory tract was reported in MCI. There was a positive correlation between UPSIT score and FA of the superior longitudinal fasciculus (SLF). A negative correlation between UPSIT and MD of the SLF was reported. We correlated olfactory identification deficits with white matter tract integrity within the context of amnestic disorders to: (1) assess whether amnestic disorders (aMCI or AD) are associated with disturbances in white matter tract integrity and (2) assess whether olfactory identification deficits are associated with greater white matter tract impairment within groups. Methods: Cross sectional structural analysis of 3T MRI with a 25-direction DTI sequence of 66 subjects (26 AD, 15 MCI, 25 HC) was performed. Diagnosis, age and ApoE genotype were added to the models as appropriate. Smellers were defined as >¼7 correct answers on the 10 item subset of the University of Pennsylvania Smell Identification Test (UPSIT) and non-smellers as <7 correct answers. The cutoff of 7 was selected based on the ROC/AUC to optimize sensitivity and specificity. Imaging data were processed and analyzed using FSL 5.0. Subject level means for FA, MD, l1 and RD were calculated from white matter skeletons. As a post hoc analysis, subject level means for FA, MD, l1 and RD were also calculated from the olfactory tract ROI skeleton. A voxel-based analysis of white matter tract integrity was conducted using TBSS. Results: There was a significant decrease of FA on subject level means of DTI skeletons in AD patients with respect to HC (p¼ 0.037). Furthermore, MD, l1 and RD were all significantly increased in both MCI (P¼0.002, 0.001, 0.005, respectively) and AD (p<0.0001 for MD, l1, RD) compared with HC. There were no statistically significant differences between MCI and AD. With respect to subject level means within the ROI skeleton of the olfactory tract, impairment in olfactory identification were associated with decreased FA in olfactory identification deficits (p¼0.007) and increased RD (p¼0.048). There were trends toward statistical significance with respect to both MD and l1 (p¼0.052, 0.07, respectively). TBSS analyses have demonstrated widespread statistically significant difference in MD between ‘smellers’ and ‘non-smellers’ within the Alzheimer’s group. Conclusions: These findings suggest that there is a loss of white matter tract integrity in both MCI and AD, with respect to healthy controls, with no statistically significant differences between the two amnestic disorders detected in this study. The lack of statistical difference between MCI and AD may be a result of limited statistical power. White matter tract integrity in the olfactory tract of subjects with olfactory identification deficits within the AD group was lost, supporting olfactory system neurodegeneration. These findings suggest that white matter tract impairment is present in amnestic disorders, and these changes may occur prior to clinical progression to AD. Markers for decreased white matter tract integrity within the olfactory tract provides a potential neuroanatomical correlate to the olfactory impairment commonly reported in amnestic disorders.
Am J Geriatr Psychiatry 23:3, Supplement 1
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