Estimating County Level Health Indicators Using Spatial Microsimulation.

Given the importance of understanding health outcomes at fine spatial scales, iterative proportional fitting (IPF), a form of small area estimation, was applied to a fixed number of health-related variables (obesity, overweight, diabetes) taken from regionalized 2019 survey responses (n = 5474) from the Idaho Behavioral Risk Factor Surveillance System (BRFSS). Using associated county-level American Community Survey (ACS) census data, a set of constraints, which included age categorization, race, sex, and education level, were used to create county-level weighting matrices for each variable, for each of the seven (7) Idaho public health districts. Using an optimized modeling construction technique, we identified significant constraints and grouping splits for each variable/region, resulting in estimates that were internally and externally validated. Externally validated model results for the most populated counties showed correlations ranging from .79 to .85, with p values all below .05. Estimates indicated higher levels of obesity and overweight individuals for midsouth and southwestern Idaho counties, with a cluster of higher diabetes estimates in the center of the state (Gooding, Lincoln, Minidoka, and Jerome counties). Alternative external sources for health outcomes aligned extremely well with our estimates, with wider confidence intervals in more rural counties with sparse populations.

Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression.

OBJECTIVE: This study tests the hypothesis that the use of semantic organizational strategy during the free-recall phase of a verbal memory task predicts remission of geriatric depression. METHODS: Sixty-five older patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7 for 2 consecutive weeks and no longer meeting the DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25-min delay was examined in a regression with age and education as covariates. RESULTS: Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04-1.54); χ(2) = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001). CONCLUSIONS: Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response.

Executive function and short-term remission of geriatric depression: the role of semantic strategy.

BACKGROUND: This study tested the hypothesis that use of semantic organizational strategy in approaching the Mattis Dementia Rating Scale (MDRS) complex verbal initiation/perseveration (CV I/P) task, a test of semantic fluency, is the function specifically associated with remission of late-life depression. METHOD: Seventy elders with major depression participated in a 12-week escitalopram treatment trial. Neuropsychologic performance was assessed at baseline after a 2-week drug washout period. Patients with a Hamilton Depression Rating Scale Score ≤7 for 2 consecutive weeks and who no longer met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were considered to be remitted. Cox's proportional hazards survival analysis was used to examine the relationship between subtests of the I/P, other neuropsychologic domains, and remission rate. Participants' performance on the CV I/P subscale was coded for perseverations, and use of semantic strategy. RESULTS: The relationship between the performance on the CV I/P subscale and remission rate was significant. No other subtest of the MDRS I/P evidenced this association. There was no significant relationship between speed, confrontation naming, verbal memory, or perseveration with remission rate. Remitters' use of verbal strategy was significantly greater than nonremitters. CONCLUSIONS: Geriatric depressed patients who showed decrements in performance on a semantic fluency task showed poorer remission rates than those who showed adequate performance on this measure. Executive impairment in verbal strategy explained performance. This finding supports the concept that executive functioning exerts a "top down" effect on other basic cognitive processes, perhaps as a result of frontostriatal network dysfunction implicated in geriatric depression.

Hippocampal volumes and the brain-derived neurotrophic factor val66met polymorphism in geriatric major depression.

OBJECTIVES: structural abnormalities in the hippocampus have been implicated in the pathophysiology of major depressive disorder (MDD). The brain-derived neurotrophic factor (BDNF) val66met polymorphism may contribute to these abnormalities and therefore confer vulnerability to MDD. This study examined whether there is a relationship among BDNF genotype, hippocampal volumes, and MDD in older adults. METHODS: thirty-three older adults with MDD and 23 psychiatrically normal comparison subjects were studied. Structural magnetic resonance imaging analysis was used to quantify hippocampal volumes. A repeated-measures analysis of covariance examined the relationships among BDNF val66met (val/val, met carrier), diagnosis (depressed, nondepressed), and hippocampal volumes (right, left). Age, gender, education, and whole brain volume were included as covariates. RESULTS: elderly MDD BDNF val/val homozygotes had significantly higher right hippocampal volumes compared with nondepressed val/val subjects. However, there was no difference between the depressed and healthy nondepressed met carriers. In addition, depressed met carriers had an earlier age of onset of depressive illness than val/val homozygotes, but age of onset did not moderate the relationship between hippocampal volumes and MDD diagnosis. CONCLUSION: these results provide preliminary evidence of a neuroprotective role of the val/val genotype, suggesting that neurotrophic factor production protects against pathophysiological processes triggered by depression in older adults with later age of onset of MDD. The BDNF val66met polymorphism may play a salient role in structural alterations of the hippocampus in older adults with MDD.

Cognitive control in late-life depression: response inhibition deficits and dysfunction of the anterior cingulate cortex.

OBJECTIVES: Geriatric depression is associated with frontolimbic functional deficits, and this frontal dysfunction may underlie the marked executive control deficits often seen in this population. The authors' goal was to assess the integrity of frontal cortical functioning in geriatric depression, while these individuals performed a standard cognitive control task. The N2 component of the event-related potential (ERP), an evoked response generated within the anterior cingulate cortex (ACC), is significantly enhanced when nondepressed individuals successfully inhibit a response, providing an excellent metric of frontal inhibitory function. DESIGN: The authors used a variant of a demanding Go/NoGo task-switching paradigm that required participants to inhibit response execution during NoGo trials by overcoming a potent response tendency established by frequent Go trials. PARTICIPANTS: The authors compared a cohort of depressed geriatric outpatients (N = 11) with a similarly aged group of nondepressed participants (N = 11). MEASUREMENTS: Reaction times, accuracy, and high-density event-related potential recordings from a 64-channel electrode montage were obtained. RESULTS: A significantly enhanced N2 to NoGo trials was observed in nondepressed elderly participants, with generators localized to the ACC. In contrast, this enhancement was strongly reduced in the depressed sample. Source analysis and topographic mapping pointed to a displacement of N2 generators toward more posterior areas of the middle frontal gyrus in depressed subjects. CONCLUSIONS: Findings confirm previous reports of an inhibitory control deficit in depressed elderly who show significantly increased rates of commission errors (i.e., failures to inhibit responses on NoGo trials). Electrophysiologic data suggest underlying dysfunction in ACC as the basis for this deficit.

Anterior cingulate cortical volumes and treatment remission of geriatric depression.

BACKGROUND: Structural abnormalities of the anterior cingulate cortex (ACC) may interfere with the interaction of cortical and limbic networks involved in emotional regulation and contribute to chronic depressive syndromes in the elderly. This study examined the relationship of regional anterior cingulate cortical volumes with treatment remission of elderly depressed patients. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit smaller anterior cingulate gray matter volumes than patients who remitted. METHODS: The participants were 41 non-demented individuals with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for at least 2 consecutive weeks. The patient sample consisted of 22 depressed patients who achieved remission during the study and 19 depressed patients who remained symptomatic. High-resolution magnetization-prepared rapidly acquired gradient echo (MPRAGE) sequences were acquired on a 1.5 T scanner and regional ACC volumes were manually outlined (dorsal, rostral, anterior subgenual, and posterior subgenual). RESULTS: Repeated measure analyses revealed that patients who failed to remit following escitalopram treatment had smaller dorsal and rostral anterior cingulate gray matter volumes than patients who remitted, whereas subgenual cortical volumes did not differ between the groups. CONCLUSIONS: Structural abnormalities of the dorsal and rostral anterior cingulate may perpetuate late-life depression.

Microstructural white matter abnormalities and remission of geriatric depression.

OBJECTIVE: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. METHOD: The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. RESULTS: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. CONCLUSIONS: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.

Executive dysfunction in elderly bipolar manic patients.

OBJECTIVE: This study used neuropsychological measures of executive skills to examine the functioning of frontostriatal networks in elderly bipolar patients. DESIGN: The authors hypothesized that elders with bipolar mania would exhibit poor executive functions relative to both elderly comparison subjects and depressed patients. SETTING: The study was conducted in the geriatric psychiatry services of a university hospital. PARTICIPANTS: Nondemented elders: 14 with bipolar disorder I, manic (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), 14 with unipolar major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and 14 nonpsychiatric comparison (NC) subjects. MEASUREMENTS: Executive functions were assessed with the initiation/perseveration subscale of the Dementia Rating Scale and the manual Go/No-Go tasks from the extended initiation/perseveration scale. RESULTS: Manic elders demonstrated poor performance on tasks of initiation/perseveration and response inhibition, and performed significantly worse than both depressed patients and NC subjects. In this sample, there was no evidence for a relationship between severity of manic symptoms and executive performance. CONCLUSION: These findings extend the observation that elderly bipolar manic patients have deficits in executive functioning compared with NC samples and provide evidence that the executive deficits demonstrated by bipolar manic elders can be more severe than those in unipolar depressed elders. As executive functions require frontostriatal integrity, these observations support investigation of specific frontostriatal network abnormalities in late-life bipolar disorder.

Macromolecular white matter abnormalities in geriatric depression: a magnetization transfer imaging study.

OBJECTIVE: Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression. DESIGN: The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions. SETTING: The study was conducted in a university-based, geriatric psychiatry clinic. PARTICIPANTS: Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed. MEASUREMENT: Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate. RESULTS: Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions. CONCLUSION: These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions.

Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050.

OBJECTIVE: To estimate the projected population of US adults aged 18 years or older with lifetime experience of doctor-diagnosed depressive disorder from 2005-2050. METHODS: Based on nationally representative survey data from the year 2006 Behavioral Risk Factor Surveillance Survey (BRFSS), prevalence estimates of doctor-diagnosed depression (minor or major, and dysthymia) were weighted to incorporate the complex sampling design and increase generalizability of the findings. The weighted prevalence data by age and sex in 2006 were then used to estimate the projected adult population with lifetime experience of depressive disorder based on the sex-specific US Census national population projections from year 2005-2050. RESULTS: In year 2006 the (weighted) prevalence of lifetime experience of depressive disorder was 15.7% among 188,292 respondents aged 18 years or older. Female prevalence was 20.6%, which was about twice as high as the prevalence among males (11%). From year 2005-2050, the total number of US adults with depressive disorder will increase from 33.9 million to 45.8 million, a 35% increase. The increase is projected to be greater in the elderly population aged >or=65 years (3.8-8.2, a 117% increase) than in the young population aged <65 years (30.1-37.7, a 25% increase). CONCLUSIONS: By year 2050, approximately 46 million US adults aged 18 years or older will be diagnosed with a depressive disorder. The increase will be more pronounced in adults aged 65 or older. Prevention, detection, and treatment of depressive disorders might attenuate the magnitude of this estimate.

White-matter integrity predicts stroop performance in patients with geriatric depression.

BACKGROUND: This study tested the hypothesis that microstructural white matter abnormalities in frontostriatal-limbic tracts are associated with poor response inhibition on the Stroop task in depressed elders. METHOD: Fifty-one elders with major depression participated in a 12-week escitalopram trial. Diffusion tensor imaging was used to determine fractional anisotropy (FA) in white matter regions. Executive function (response inhibition) was assessed with the Stroop task. Voxelwise correlational analysis was used to examine the relationship between Stroop performance and fractional anisotropy. RESULTS: Significant associations between FA and Stroop color word interference were evident in multiple frontostriatal-limbic regions, including white matter lateral to the anterior and posterior cingulate cortex and white matter in prefrontal, insular, and parahippocampal regions. CONCLUSIONS: These findings suggest that microstructural white matter abnormalities of frontostriatal-limbic networks are associated with executive dysfunction of late-life depression. This observation provides the rationale for examination of specific frontostriatal-limbic pathways in the pathophysiology of geriatric depression.

Event-related potentials in an emotional go/no-go task and remission of geriatric depression.

Anterior cingulate integrity may be required for antidepressant response. To assess anterior cingulate processes related to treatment response, we studied error-related negativity and error positivity produced during an emotional go/no-go challenge, a task activating the rostral anterior cingulate. Twelve elderly patients with major depression, treated with escitalopram 10 mg daily, were studied. Patients who remained symptomatic after 8 weeks of treatment had larger error-related negativity and smaller error positivity amplitude compared with patients who achieved remission. The error-related negativity is elicited during conflict detection and the error positivity reflects the emotional reaction to error. Thus, these findings suggest that two distinct conflict-processing functions of the anterior cingulate are important for antidepressant response of geriatric depression.

An examination of neurocognition and symptoms as predictors of post-hospital community tenure in treatment resistant schizophrenia.

Neurocognition and psychopathology are robust predictors of community functioning and relapse/rehospitalization in schizophrenia. Existing studies are however limited because they have ignored the most chronic, treatment-resistant patients. Moreover, the prediction of functional outcomes has yet to be extended to the duration of community tenure, an indicator of the capacity of chronically-hospitalized patients to gain traction in the community. The current study examined neurocognition and symptom severity at discharge as potential predictors of community tenure in chronically-hospitalized treatment-resistant patients. The study recruited 90 people with treatment-resistant schizophrenia who received services on an inpatient unit. Participants completed measures of psychopathology and neurocognition prior to discharge. Following discharge, participants were tracked at current residences six months and one year post-discharge to assess community tenure. The percentage of individuals who continued to live in the community at 12-month follow-up was 51%. Severe negative symptoms but not neurocognitive impairment or positive symptoms was a significant predictor of shorter post-hospital community tenure. Of the negative symptoms domain, anhedonia-asociality proved to be the most relevant predictor of community tenure in the sample. The capacity to elicit goal-directed behaviors in response to anticipated physical and social rewards may be an important treatment target for sustaining community tenure.

Executive dysfunction and the course of geriatric depression.

BACKGROUND: Executive dysfunction is common in geriatric depression and persists after improvement of depressive symptoms. This study examined the relationship of executive impairment to the course of depressive symptoms among elderly patients with major depression. METHODS: A total of 112 nondemented elderly patients with major depression participated in an 8-week citalopram trial at a target daily dose of 40 mg. Executive functions were assessed with the initiation/perseveration subscale of the Dementia Rating Scale and the Stroop Color-Word test. Medical burden was rated with the Cumulative Illness Rating Scale. RESULTS: Both abnormal initiation/perseveration and abnormal Stroop Color-Word scores were associated with an unfavorable response of geriatric depression to citalopram. In particular, initiation/perseveration scores below the median (< or =35) and Stroop scores at the lowest quartile (< or =22) predicted limited change in depressive symptoms. Impairment in other Dementia Rating Scale cognitive domains did not significantly influence the outcome of depression. CONCLUSIONS: Executive dysfunction increases the risk for poor response of geriatric depression to citalopram. Because executive functions require frontostriatal-limbic integrity, this observation provides the rationale for investigation of the role of specific frontostriatal-limbic pathways in perpetuating geriatric depression. Depressed elderly patients with executive dysfunction require vigilant clinical attention because they might be at risk to fail treatment with a selective serotonin reuptake inhibiting antidepressant.

Frontal white matter microstructure and treatment response of late-life depression: a preliminary study.

OBJECTIVE: This study tested the hypothesis that microstructural abnormalities in white matter areas of the brain containing frontostriatal tracts are associated with a low rate of remission of geriatric depression. METHOD: Thirteen older patients with major depression received open, but controlled, treatment with citalopram at a target daily dose of 40 mg for 12 weeks. Diffusion tensor imaging was used to determine fractional anisotropy in preselected white matter regions. RESULTS: Survival analysis with Cox's proportional hazards model revealed that lower fractional anisotropy of the right and the left frontal white matter regions 15 mm above the anterior commissure-posterior commissure plane was associated with a low remission rate after age was considered. Remission was not significantly associated with fractional anisotropy of lower frontal regions or a temporal region. CONCLUSIONS: Microstructural white matter abnormalities lateral to the anterior cingulate may be associated with a low rate of remission of geriatric depression.

Assessing behavioral health using OASIS: part 2: cognitive impairment, problematic behaviors, and anxiety.

This article is the second of a two-part series on assessing behavioral health in adult and elderly home care patients using OASIS. Part 1 presented an assessment approach for depressive symptoms and suicidality. This article presents the assessment of cognitive impairment, problematic behaviors, and anxiety using OASIS as a framework and stresses the importance of direct questioning. Case scenarios and guidelines for referral for further evaluation and possible treatment are provided.

Functional connectivity in the cognitive control network and the default mode network in late-life depression.

BACKGROUND: Abnormalities have been identified in the Cognitive Control Network (CCN) and the Default Mode Network (DMN) during episodes of late-life depression. This study examined whether functional connectivity at rest (FC) within these networks characterizes late-life depression and predicts antidepressant response. METHODS: 26 non-demented, non-MCI older adults were studied. Of these, 16 had major depression and 10 had no psychopathology. Depressed patients were treated with escitalopram (target dose 20 mg) for 12 weeks after a 2-week placebo phase. Resting state time series was determined prior to treatment. FC within the CCN was determined by placing seeds in the dACC and the DLPFC bilaterally. FC within the DMN was assessed from a seed placed in the posterior cingulate. RESULTS: Low resting FC within the CCN and high resting FC within the DMN distinguished depressed from normal elderly subjects. Beyond this "double dissociation", low resting FC within the CCN predicted low remission rate and persistence of depressive symptoms and signs, apathy, and dysexecutive behavior after treatment with escitalopram. In contrast, resting FC within the DMN was correlated with pessimism but did not predict treatment response. CONCLUSIONS: If confirmed, these findings may serve as a signature of the brain's functional topography characterizing late-life depression and sustaining its symptoms. By identifying the network abnormalities underlying biologically meaningful characteristics (apathy, dysexecutive behavior, pessimism) and sustaining late-life depression, these findings can provide a novel target on which new somatic and psychosocial treatments can be tested.

BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression.

OBJECTIVE: The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNF(val/met) status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. METHOD: Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. RESULTS: BDNF(met) carriers were more likely to achieve remission than BDNF(val/val) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNF(val66met) status and microstructural abnormalities in predicting remission. LIMITATIONS: Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. CONCLUSIONS: Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/val) homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF(val66met) and remission is due to different effects of BDNF in brain structures related to mood regulation.

Visual inspection of independent components: defining a procedure for artifact removal from fMRI data.

Artifacts in functional magnetic resonance imaging (fMRI) data, primarily those related to motion and physiological sources, negatively impact the functional signal-to-noise ratio in fMRI studies, even after conventional fMRI preprocessing. Independent component analysis' demonstrated capacity to separate sources of neural signal, structured noise, and random noise into separate components might be utilized in improved procedures to remove artifacts from fMRI data. Such procedures require a method for labeling independent components (ICs) as representing artifacts to be removed or neural signals of interest to be spared. Visual inspection is often considered an accurate method for such labeling as well as a standard to which automated labeling methods are compared. However, detailed descriptions of methods for visual inspection of ICs are lacking in the literature. Here we describe the details of, and the rationale for, an operationalized fMRI data denoising procedure that involves visual inspection of ICs (96% inter-rater agreement). We estimate that dozens of subjects/sessions can be processed within a few hours using the described method of visual inspection. Our hope is that continued scientific discussion of and testing of visual inspection methods will lead to the development of improved, cost-effective fMRI denoising procedures.