Geriatric Major Depressive Disorder Research Articles

Associations between worse executive control and greater fall risk in Geriatric Major Depressive Disorder

<h3>Introduction</h3> Psychomotor disturbances (e.g. psychomotor retardation/agitation) are a core feature of major depressive disorder (MDD) and when present, predict poor treatment outcomes. Psychomotor impairment in late life MDD (LLD) reflect deficits in motor and sensorimotor function, which impair balance control in older adults (OAs). When compared to healthy OAs, those with LLD are ∼35% more likely to fall, develop a fear of falling, and avoid physical activity, all of which predict early mortality. OAs who fall lose their independence and have a worse quality of life, and the rate of deaths from falls is rising. The association between LLD and fall-risk is complicated by pharmacologic treatments that intensify fall-risk; anti-depressants decrease walking speed and increase fall-risk equivalent to antipsychotic and benzodiazepine medications. A poor understanding of <i>when, why, and how</i>falls occur in LLD has led to a knowledge gap regarding relationships between psychomotor disturbance, LLD and fall-risk. Complicating matters, roughly 40% of patients with LLD suffer from cognitive difficulty called cognitive control deficits (CCD) that predispose them to poor clinical outcomes like disability, SSRI treatment resistance, relapse, and suicide. Converging evidence suggests a common neurobiological etiology underlie LLD, CCD and fall-risk. OAs with CCD are three times more likely to fall than their healthy peers and are more susceptible to recurrent falls. OAs with CCD are more likely to exhibit worse health outcomes and mobility deficits suggesting greater fall-risk. The co-occurrence and clinical relevance of these phenomena provides a unique opportunity for investigation. The purpose of this study was to quantify associations between CCD and fall-risk in treatment resistant LLD. Our hypothesis was LLD patients who fail to respond to treatment with SSRI/SNRI would be more likely to exhibit CCD, which would be negatively associated with fall history. <h3>Methods</h3> Participants were aged ≥ 65 years and met DSM-IV-TR/Research Diagnostic criteria for unipolar MDD (Hamilton Depression Rating Scale (HDRS)>19) in an interview with a licensed clinician (SM) despite treatment with SSRI/SNRI antidepressants for ≥8 weeks. Data collection was part of screening for a larger intervention study at Weill Cornell Medical College. Exclusion criteria included: No diagnosis or evidence of dementing disorder (Mini-Mental State Examination (MMSE) score <25), reporting psychotic features/disorders or acute suicidal ideation, severe medical illness, or neurological disorders. Fall history was determined with a brief survey. Participants completed a neuropsychological battery including the Trail Making Test; a test of cognitive flexibility that is associated with fall risk in OA. Participants who reported a fall one or more times in the preceding year were classified as a ‘faller', those that had not fallen were ‘non-fallers'. Group differences (fallers, non-fallers) in CCD were compared with independent t-tests. Logistic regression predicted fall status with CCD performance outcomes, while controlling for gender. <h3>Results</h3> A total of 30 OA participants with MDD were included in the analysis. Approximately 1/3 of our OA participants with MDD reported falling within the last year (<i>n</i> = 9). Fallers exhibited significantly poorer cognitive control as determined by TMT B and D TMT (both <i>p <</i> 0.001). Logistic regression including gender as a covariate showed D TMT significantly predicted fall status, Gender ß = -0.014, <i>p</i> = 0.918, and Faller status: ß = 0.746, <i>p</i> < 0.001. <h3>Conclusions</h3> The purpose of this study was to estimate the risk of falling in treatment resistant LLD and examine the relationship between CCD and fall risk in depressed OA. Our results demonstrate that in treatment resistant LLD, patients on adequate dosages of SSRI/SNRI antidepressants, roughly one third of patients have fallen within the last year, and that CCD may have a strong independent influence on rates of falling. This rate of falls is consistent with existing reports of fall-risk in community dwelling OAs and OAs with MDD. Our preliminary results suggest that CCD is an important factor that catalyzes fall-risk in LLD, and highlight yet another vulnerability of treatment resistant LLD patients. Though this is a preliminary retrospective study, our results suggest that clinicians may improve prediction of fall risk in LLD patients by assessing CCD, with a short, paper-pencil test that can be administered bedside. Given the new NIMH mandate to quantify features of sensorimotor function across psychiatric conditions, we propose that future investigations of LLD include objective, dimensional, large-scale assessment of motor behavior that can be integrated with other objective assessments (e.g. cognitive, functional, affective). If the associations between CCD and falls prove robust in LLD patients, CCD could serve as an intervention target to reduce fall-risk, depression, and other related negative clinical sequalae. <h3>Funding</h3> Morimoto: K 23 MH 095830, UL1TR000457 Alexopolous: R01 MH065653, P50 MH113838

PICALM mRNA Expression in the Blood of Patients with Neurodegenerative Diseases and Geriatric Depression.

Background: Phosphatidylinositol-binding clathrin assembly protein (PICALM) is a validated genetic risk factor for late-onset Alzheimer’s disease (AD) and is associated with other neurodegenerative diseases. However, PICALM expression in the blood of neurodegenerative diseases remains elusive. Objective:This study aimed to assess the usefulness of PICALM expression levels in the blood of patients with AD, Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and geriatric major depressive disorder (MDD) as a diagnostic biomarker.Methods:In total, 45, 20, 21, and 19 patients with AD, PD, DLB, and geriatric MDD, respectively, and 54 healthy controls (HCs) were enrolled in the study. Expression data from Gene Expression Omnibus database (GSE97760), (GSE133347) and (GSE98793), (GSE48350), and (GSE144459) were used to validate the ability of biomarkers in the blood of patients with AD, PD, geriatric MDD, and a postmortem human AD brain and animal model of AD (3xTg-AD mouse), respectively.Results: PICALM mRNA expression in human blood was significantly increased in patients with AD compared with that in HCs. PICALM mRNA expression and age were negatively correlated only in patients with AD. PICALM mRNA expression in human blood was significantly lower in patients with PD than in HCs. No changes in PICALM mRNA expression were found in patients with DLB and geriatric MDD. Conclusion: PICALM mRNA expression in blood was higher in patients with AD, but lower in patients with PD, which suggests that PICALM mRNA expression in human blood may be a useful biomarker for differentiating neurodegenerative diseases and geriatric MDD.

Low-Charge Electrotherapy in Geriatric Major Depressive Disorder Patients: A Case Series.

To examine the feasibility of low-charge electrotherapy (LCE) in treating geriatric major depressive disorder (MDD) patients. Bi-temporal LCEs (approximately 25 mC) were performed with an electroconvulsive therapy (ECT) instrument three times per week. We used the Hamilton Depression Scale 17 (HAMD-17) and the Hamilton Anxiety Scale (HAMA) to assess the effects of LCE and the Mini-Mental State Examination (MMSE) to evaluate the cognitive function change before and after LCE. Six visits occurred at the baseline, after LCE sessions 3, 6, and 9, after the last session, and at the end of the one-month follow-up period. Four patients were enrolled in the study. Two patients completed all LCE sessions. Two patients withdrew during the trial, one due to the adverse event of uroschesis potentially caused by atropine and the other due to her own will. All four patients completed the follow-up sessions. The HAMD-17 and HAMA scores were reduced significantly at the last LCE session and the end of the follow-up period compared with the scores at the baseline. As measured by the MMSE, cognitive impairment showed no significant changes at the last LCE session and the end of the follow-up period compared with that at the baseline. In this case series, LCE showed potential as an alternative current-based treatment for treating geriatric MDD patients. Further research is needed to assess the efficiency and safety of LCE.

Electroconvulsive therapy changes the regional resting state function measured by regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) in elderly major depressive disorder patients: An exploratory study

Electroconvulsive therapy (ECT) is the most effective and rapid treatment for severe major depressive disorder (MDD) in elderly patients. The mechanism of ECT is unclear, and studies on ECT in elderly MDD patients by resting-state functional magnetic resonance imaging are rare. Thirteen elderly MDD patients were scanned before and after ECT using a 3.0T MRI scanner. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuations (ALFF) were processed to compare resting-state function before and after treatment. Depression and anxiety symptoms of all patients abated after ECT. Decreased ReHo values in the bilateral superior frontal gyrus (SFG) were observed after ECT, and the values of right SFG significantly correlated with an altered Hamilton depression rating scale score. Increased ALFF values in the left middle frontal gyrus, right middle frontal gyrus, orbital part, and decreased ALFF values in the left midcingulate area, left precentral gyrus, right SFG/middle frontal gyrus after ECT were also observed. These results support the hypothesis that ECT may affect the regional resting state brain function in geriatric MDD patients.

Reconsidering Animal Models of Major Depressive Disorder in the Elderly.

Major depressive disorder (MDD) is a common psychiatric illness with high morbidity that poses a huge burden to healthcare systems worldwide. According to the World Health Organization, the lifetime prevalence of MDD is approximately 3–17% globally (Richards, 2011). However, after major, but limited, success with selective serotonin reuptake inhibitors (SSRIs) or serotonin–noradrenaline reuptake inhibitors, few promising therapeutic approaches have been developed from preclinical studies using current animal models of MDD, despite intensive research involving laborious methods and substantial costs. Traditionally, most research using rodent models of MDD has been conducted using relatively young adult animals, aged approximately 8 weeks, to avoid any involvement of aging-related biological factors. The major rationale of this strategy is based on epidemiological findings that the occurrence of MDD displays a robust peak in young adults rather than in the elderly (Jorm, 2000; Copeland et al., 2004; Blazer and Hybels, 2005). Further, the elderly may have aging-related factors rendering this group an inappropriate model of “genuine” MDD. A critical question is whether this strategy is indeed appropriate. Despite the consistent findings of a lower lifetime prevalence rate of MDD in the elderly than in young adults, there remain persistent doubts regarding the underdiagnosis of MDD in the elderly (Hoertel et al., 2013). It has been heavily argued that patients diagnosed with MDD in youth will often be rediagnosed with a bipolar disorder (Lish et al., 1994; Leonpacher et al., 2015). Thus, a considerable number of cases of MDD in young adults may be misdiagnosed. In addition, MDD in the elderly has distinct biological/environmental backgrounds and consequences compared with that in young adults. In this opinion article, we primarily shed light on the significance of MDD in the elderly (known as geriatric MDD or late-onset depression) and problems associated with the methodology of preclinical studies undertaken to investigate the characteristics and treatment of this disorder.

Cerebrospinal Fluid Biomarkers in Alzheimer's Disease and Geriatric Depression: Preliminary Findings from Brazil

Depression is a highly prevalent disorder in the elderly and one of the risk factors for developing dementia. The present study involves patients with Alzheimer's disease (AD), geriatric major depressive disorder (MDD) and cognitively healthy controls aiming to compare baseline cerebrospinal fluid (CSF) biomarkers. The study included 52 patients with more than 60 years of age with a diagnosis of MDD, AD, and healthy controls. All individuals underwent a medical history, physical, and neurologic examination, laboratory tests and neuropsychological assessment to rule out any clinical diseases or disorders. Measurement of CSF P-tau(181) , T-tau, and Aβ42 was performed using commercial assays (ELISA). CSF Aβ42 levels of depressed patients and normal controls were significantly higher than in AD. There was not any significant difference in measures of P-tau among the groups. T-tau, however, showed to be significantly different among the groups, with higher measures in AD group. Higher levels of P-tau were observed in four MDD patients compared with controls. CSF Aβ42, T-tau, and P-tau levels may differentiate between AD and depression in a Brazilian sample.

Late‐life depression and the death of Queen Victoria

The objective of this study was to evaluate relationships between the death of Queen Victoria and the depressive episode she experienced during the last year of her life. The last volume of Queen Victoria's personal Journal was reviewed from a geriatrician's perspective, tracing the onset and course of depressive symptoms from entries beginning on 17 August 1900 and ending on 13 January 1901, 9 days before her death. The Queen's own words are supplemented with observations from contemporaneous secondary sources. The antecedents of Queen Victoria's late-life depression, including multiple losses, disabilities, and chronic pain, taken together with the presentation of vegetative, affective, and late cognitive symptoms, suggested the presence of a distinctively geriatric major depressive disorder. The absence of any other medical condition to explain the clinical picture seemed probable but not certain. Although historians and biographers have long been aware of Queen Victoria's final depression, the emphasis has mostly been on her earlier and prolonged mourning for her husband Prince Albert. Re-examined now, the Queen's Journal suggests that a severe late-life depressive episode occurring approximately in her last 5 months contributed meaningfully to her death.

Comparison of treatment persistence, hospital utilization and costs among major depressive disorder geriatric patients treated with escitalopram versus other SSRI/SNRI antidepressants

ABSTRACTObjective: To assess treatment persistence, hospitalization outcomes and mean healthcare costs of geriatric major depressive disorder (MDD) patients treated with escitalopram compared to other selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).Research design and methods: Patients aged ≥ 65 years with at least one inpatient claim or two independent claims associated with MDD diagnosis were identified in the IHCIS National Managed Care Database (2003–2005). Patients were continuously enrolled for at least ≥ 12 months, filled at least one prescription for an SSRI/SNRI and did not use any second-generation antidepressant during the 6 months pre-index date. Unadjusted and multivariate analyses adjusting for baseline characteristics were conducted.Main outcome measures: Treatment persistence, hospitalization utilization, and average prescription drug, medical, and total healthcare costs were compared between patients initiated on escitalopram versus other SSRI/SNRIs.Results: Escitalopram-treated patients (N = 459) were less likely to discontinue treatment (HR = 0.85, p = 0.012) or switch to another second-generation antidepressant (HR = 0.76, p = 0.006) compared to patients treated with other SSRI/SNRIs (N = 1517). Escitalopram-treated patients had 39% fewer hospitalization days ( p = 0.004). Both groups had similar mean prescription drug costs ($1659 vs. $1630, p = 0.687). After controlling for baseline characteristics, escitalopram-treated patients had lower mean total medical service costs ($9425 vs. $12 703, p < 0.001) and mean total healthcare costs ($11 043 vs. $14 163, p < 0.001).Limitations: This study's limitations include its small sample size, short observational periods and exclusivity of indirect costs.Conclusions: Geriatric patients treated with escitalopram had higher treatment persistence, fewer hospitalization days and lower total healthcare costs than patients on other SSRI/SNRIs after controlling for baseline characteristics. Most of the cost savings were due to reductions in hospitalizations.

Novel Augmentation Therapy with Cilostazol for the Geriatric Major Depressive Disorder Patient with Deep White Matter Hyperintensities on T2-Weighted Brain MRI: A Case Report

In our search of a new augmentation therapy for geriatric patients with intractable depression, we administered cilostazol, an antiplatelet agent, in addition to conventional antidepressants to a patient with persistent major depressive disorder showing deep white matter hyperintensities on a T2-weighted magnetic resonance image and evaluated cerebral blood flow before and after the administration of cilostazol by 99m Tc-ethyl-cysteinate dimer single photon emission computed tomography. This patient showed improvements of depressive symptoms as well as an increase in cerebral blood flow. These findings suggest a potential efficacy of cilostazol as a new drug for use in augmentation therapy for depressed patients with deep white matter hyperintensities.

Increased tau protein differentiates mild cognitive impairment from geriatric depression and predicts conversion to dementia

Significantly increased cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated at threonine 181 tau (p-tau) levels were frequently found in patients with mild cognitive impairment (MCI) who have an increased risk of developing Alzheimer's disease (AD). Though MCI often overlaps with depressive symptoms making early diagnosis difficult, to date no CSF marker has been probed to support the differential diagnosis of geriatric major depressive disorder and MCI eventually converting to AD. CSF levels of t-tau and p-tau were determined by ELISA in 80 subjects with MCI (aging associated cognitive decline criteria), 54 patients with major depression and 24 cognitively healthy controls. Patients were reassessed after a follow-up period of at least 12 month. During follow-up, 29% of the MCI patients but only one patient with major depression converted to AD. Already at baseline converters to AD were characterized by significantly higher t-tau and p-tau levels compared to non-converters and the other diagnostic groups. Our findings demonstrate that both, CSF t-tau and p-tau levels facilitate the differential diagnosis of MCI and are of prognostic value.

Neuropsychological Differences Between Late-Onset and Recurrent Geriatric Major Depression

Executive dysfunction, possibly related to vascular pathology, has been well documented in patients with a first episode of major depressive disorder in later life (late-onset geriatric major depression). However, it is unclear whether the neuropsychological presentation differs in patients with a lifetime history of major depressive disorder (recurrent geriatric major depressive disorder). The purpose of this study was to explore differences in neuropsychological function, symptoms, and cardiovascular comorbidity between patients with late-onset and recurrent geriatric major depression. The study used a two-by-two factorial design in which one factor was current major depressive disorder (present versus absent) and the second factor was lifetime history of depression (present versus absent). Neuropsychological measures of executive functioning and episodic memory, as well as psychopathological symptoms and comorbid medical illness, were examined in a total of 116 older adults. Patients with late-onset major depressive disorder showed specific deficits in attention and executive function, whereas patients with recurrent major depressive disorder exhibited deficits in episodic memory. The rates of anhedonia and comorbid cardiovascular illness were higher in patients with late-onset geriatric major depressive disorder. In contrast to recurrent geriatric major depressive disorder, late-onset major depressive disorder is characterized by specific deficits in tasks of attention and executive function, consistent with increased anhedonia and cardiovascular comorbidity. These findings, if confirmed, suggest that recurrent and late-onset geriatric major depressive disorder may represent distinct phenomenological entities. Such phenomenological differences as a function of lifetime history of major depression can guide research in the neurophysiology, prevention, and treatment of geriatric major depressive disorder.