Cognition In Late-life Depression Research Articles

The Role of State Versus Trait Anxiety on Cognition in Older Adults With Major Depressive Disorder

ObjectiveAnxiety superimposed on late life depression (LLD) results in greater changes to prefrontal and medial temporal brain regions compared to depression alone. Yet, the combined impact of anxiety and depression on cognition in LLD has not been thoroughly investigated. The current study investigated whether annual changes in state and trait anxiety were associated with cognitive changes in older adults with major depression. We hypothesized that the presence of anxiety among older depressed adults would be associated with worse cognitive performance in the domains of memory and executive functioning over time. DesignThree-year longitudinal observational study of older adults with LLD who were offered antidepressant treatment. SettingAcademic Health Center. MethodsParticipants included 124 adults aged 60+ who met criteria for major depression at baseline. The association between anxiety and cognition was examined with separate multilevel linear models that addressed both between-subject and within-person effects of state and trait anxiety on cognitive functioning tests. ResultsIndividuals who experienced annual increases in anxiety above his/her personal average also experienced cognitive decline. Increases in state anxiety were associated with declines in memory and global cognition. By contrast, increases in trait anxiety were associated with declines in mental flexibility and memory. These findings remained significant even when controlling for changes in depression over time. ConclusionIn LLD, individual increases in state and trait anxiety were associated with cognitive declines in different domains.

59 The Impact of Anxiety on Memory Performance in Older Adults with Depression

Objective:Late life depression (LLD) refers to a diagnosis of major depressive disorder in people older than 60, and has been linked to significant cognitive impairment and increased risk of Alzheimer's disease. Although anxiety and depression are highly comorbid, the impact of anxiety on cognition in LLD is far less researched. This is important given that over 20% of middle aged and older adults endorse clinically significant chronic worry. Generalized anxiety disorder in older adults with major depression is associated with poorer cognition and worse treatment outcomes compared with those without anxiety. Therefore, the purpose of the study is to examine the role of anxiety on memory in LLD. We hypothesized that presence of anxiety among older depressed adults would be associated with worse cognitive performance over time.Participants and Methods:Participants included 124 individuals (69.4% female, 90.3% Caucasian) aged 60 or above (M = 71.5, SD = 7.4) who met criteria for major depression, single episode or recurrent. They completed the State Trait Anxiety Inventory, Montgomery Asberg Depression Rating Scale, and a measure of verbal episodic memory (WMS-IV Logical Memory) as part of a larger neuropsychological battery. Data were collected from baseline to three years as part of a larger NIMH-supported longitudinal study. Two-level linear mixed-effect models were fitted to predict memory. State and trait anxiety were used as time-varying predictors. The between-person (level 2) and within-person (level 1) effects of anxiety on memory were assessed controlling for the time trend, age, education, gender, race, and change in depression over time.Results:Plot trajectories across variables revealed a negative correlation such that as anxiety decreased, memory improved over time. Hierarchical linear mixed-effect models revealed that average state anxiety was a marginally significant between-person (level2) predictor for memory [B=-0.041, t(128)=-1.8, p=0.083]. Individuals with greater average state anxiety were more likely to experience memory decline compared to those with lower average state anxiety. In addition, the within-person effect (level 1) of state anxiety was significant [B=-0.096, t(253)=-2.7, p=0.007]. As an individual's anxiety increased over time, their memory declined. Trait anxiety showed a significant within-person effect on memory [B=-0.087, t(254)=-2.0, p=0.048], but a non-significant between-person effect [B=-0.005, t(124)=-0.06, p=0.95].Conclusions:Anxiety appears to increase the risk of memory decline in older adults with major depression, a cohort who are already at risk of cognitive decline. Changes in anxiety increased risk of memory decline even when accounting for changes in depression over time. Although the causal link between anxiety and cognitive impairment remains unclear, it is possible that anxiety and worry may compete for cognitive resources necessary for demanding tasks and situations, detracting from abilities, such as attention and working memory. Older adults with depression may also have difficulty coping adaptively with anxiety, which may negatively affect cognition. Finally, presence of anxiety may represent a form of mild behavioral impairment, a prodrome of cognitive decline leading to dementia. Overall, the present study highlights the negative impact of anxiety on memory performance, indicating that treatment interventions targeting anxiety in older adults are essential to help prevent cognitive decline.

033 The effect of sleep disturbance on cognition in late-life depression

Abstract Introduction Late-life depression is the most common psychiatric disorder in older adults and is associated with cognitive deficits, however, the role of sleep disturbance in cognitive deficits is poorly defined. In the current study we aimed to examine sleep macro and micro-architecture differences between those with late-life depression and controls. Secondly, we sought to determine how sleep changes relate to clinical memory and executive function measures in those with late-life depression and controls. Methods Using prior clinical data, this retrospective study assessed adults >50 years who had completed an overnight PSG study and comprehensive psychiatric, neuropsychological, and medical assessment. Memory performance was measured using the Weschler Memory Scale logical Memory 1 and 2 components, Rey Auditory Verbal Learning Test (Senior) 30-minute recall and Rey Complex Figure 3-minute recall. Executive function was defined by z scores from Trail Making Test, D-KEFS Stroop Test and Controlled Oral Word Association Test. The sample comprised of 71 depressed participants, defined by a Geriatric Depression Scale score ≥6, and 101 non-depressed participants (GDS <6 and no lifetime history of depression using DSM-IV criteria). Results Contrary to our hypothesis no significant macroarchitectural differences were observed between the groups. Less time spent in slow-wave sleep (SWS) was associated with worse delayed memory recall scores in the depression group (z=.342, p=0.008) although this was not seen in the control group. SWS and slow wave activity (SWA) were not related to measures of executive function performance. Depressed participants demonstrated a reduced level of sleep spindles (Dep= 159 ±142.8, con= 213±163, p=.03) although there were no associations with memory outcomes. Conclusion Compared to younger adults with depression, macroarchitectural differences in those with late-life depression are not as pronounced, due to a reduction of SWS and SWA power as a function of ageing. The efficiency of SWS hippocampal dependent memory processes in depression may be reduced, therefore, more time spent in SWS is related to better memory performance. This study assessed the density of sleep spindles but not spindle and slow wave oscillation coupling which may be more important for hippocampal dependent memory. Support (if any):

The Longitudinal Effects of Moderate Alcohol Use on Mood and Cognition in Late Life Depression

<h3>Introduction</h3> Alcohol use disorder interferes with antidepressant treatment in older adults with major depression (LLD) and is associated with suicidal ideation. Less is known about the effects of moderate alcohol use in LLD on mood and cognitive outcomes over time. Much of the evidence on alcohol use and cognition and mood stems from epidemiological research and not clinical studies of depressed older adults. The purported benefits of moderate alcohol use on older adults' cognitive functioning have often been reported. Yet, not all studies report a positive association between moderate alcohol use and cognitive functioning, and there is also other evidence to suggest moderate alcohol use is correlated with markers of poorer brain health in older adults (e.g., atrophy). In respect to mood, epidemiological research suggests little to no association between moderate alcohol use and depression in older adults or even an inverse association with increased social interactions as a mediator. Given the times at conflicting evidence and the lack of longitudinal studies in well-defined clinical samples, we hypothesized that depressed older adults who were moderate drinkers would experience greater cognitive decline compared to depressed non-drinkers. We also hypothesized that moderate alcohol use would have a detrimental effect on depression illness course in older adults with LLD. <h3>Methods</h3> This study used data from Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. NCODE participants underwent annual neuropsychological evaluations with the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) cognitive battery as well as other tests of executive functioning and processing speed (e.g., Trail Making Test). Participants also underwent annual depression severity ratings with a geriatric psychiatrist using the Montgomery Asberg Depression Rating Scale (MADRS). We used patients self-reported alcohol use at the time of study entry and characterized them as either abstainers (n=81) and moderate drinkers (n=30). We were also able to define a small sample of risky drinkers (n=10) and included this group for exploratory reasons. Alcohol use was based upon NIAAA guidelines for older adult alcohol consumption. Risky alcohol use exceeded NIAAA alcohol consumption guidelines for older adults (meaning >=3 drinks per day or >=8 drinks per week) and moderate alcohol use was defined as <= 2 drinks per day or <=7 drinkers per week). We used mixed linear modeling to investigate change in depression and cognition among groups over time. These analyses included NCODE subjects who were followed for up to 5 years and adjusted for relevant demographics. <h3>Results</h3> In terms of cognition, we found that the total CERAD score of moderate and heavy drinkers significantly declined compared to no alcohol use patients (e.g.,moderate alcohol use x time interaction term estimate = -.00410, DF = 898, t = -5.02, <i>p</i> < .001) . We also found significant declines in Trails A performance among moderate alcohol users compared to the other groups. The MADRS score of moderate alcohol users was also found to decrease at a significantly higher rate compared to other patient groups. <h3>Conclusions</h3> Moderate alcohol consumption appears to have a beneficial impact on depression severity and a detrimental impact on cognitive functioning in LLD patients followed for upwards of five years. Larger samples are needed to confirm the findings in this small and exploratory study.

Greater baseline subjective attentional complaints predict poorer 8-week antidepressant response in late-life depression

<h3>Introduction</h3> Late-life depression (LLD) is characterized by both subjective cognitive complaints and objective cognitive deficits, most notably in executive functions. Worse cognitive performance, including in the executive function domain, is associated with poor antidepressant treatment outcomes. While executive-based cognitive complaints are similarly associated with poor treatment outcomes, the relationship between other subjective cognitive complaints and antidepressant response is not as clear. This may be particularly relevant for subjective attentional complaints, a common finding and clinical diagnostic criterion for Major Depressive Disorder. <h3>Methods</h3> Eighty-eight adults with LLD were recruited (mean age = 66.07 ± 4.49, 61% female, baseline mean Montgomery-Asberg Depression Rating Scale (MADRS) = 26.38 ± 5.46) and underwent an 8-week antidepressant trial. Subjective cognitive complaints were assessed with the following scales: Attentional Control Scale (ACS, focusing in-depth on attention), the WHODAS 2.0, domain 1 (focusing largely on attentional abilities), and the PROMIS Cognitive Abilities and Concerns (focusing on general / broad-based cognitive abilities). Antidepressant response was determined via the change in MADRS scores from baseline to week 8. Separate linear regressions examined the relationship between subjective cognitive complaints and change in MADRS scores, controlling for age, sex, baseline MADRS, and treatment arm. <h3>Results</h3> After covariate adjustment, ACS and WHODAS scores significantly predicted antidepressant response (<i>ß =</i> -0.42<i>, p=</i> 0.02 and <i>ß =</i> 0.57<i>, p=</i> 0.03, respectively), such that greater subjective attentional complaints at baseline were related to less improvement in MADRS scores. General cognitive complaints via the PROMIS were not significantly associated with antidepressant response. Follow-up analyses decomposing the ACS into its two subscales found that the change in MADRS scores was significantly related to attentional shifting (<i>ß = -</i>0.79, <i>p</i> = 0.01), but not focusing (<i>ß =</i> -0.57, <i>p</i> = 0.06), complaints. <h3>Conclusions</h3> Results highlight the importance of assessing for subjective cognitive complaints in LLD, particularly in the domain of attention, as their presence at baseline may be related to treatment response. Further research is needed to better understand the relationship between subjective and objective cognition in LLD, their relationship with treatment response and other outcomes, as well as underlying mechanisms. <h3>Funding</h3> R01MH102246

The Impact of Amyloid Burden and APOE on Rates of Cognitive Impairment in Late Life Depression.

Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden. Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden. LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOEɛ4 genotype was associated with worse performance on Logical Memory I (p = 0.022); these relationships did not differ between LLD and ND. LLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.

RESULTS OF THE ADNI-DEPRESSION STUDY: Session 323

Results Of The ADNI-Depression Study. Overview: Late life depression (LLD) is one of the most common mental health disorders with which older patients are afflicted. LLD is complicated by the common co-occurrence of cognitive impairment (CI). Estimates suggest as many as 50-60% of older depressed patients may have mild cognitive deficits however the mechanisms contributing to CI are unclear. The ADNI-Depression (ADNI-D) Study is a 5-year two-site (University of California San Francisco and the University of Pittsburgh) NIMH sponsored study of late life depression. The study aims to characterize cognitive functioning patients with LLD and clarify neurobiological mechanisms contributing to cognitive impairment and accelerated cognitive decline in this patient population. The ADNI -D study partners with the Alzheimer's Disease Network Initiative (ADNI) and utilizes its core labs for data management, brain imaging, and biomarker assessments. The ADNI D study has been designed to focus on evaluating the impact of reduced cerebral blood flow, cortical atrophy, white matter disease, and amyloid deposition on cognitive impairment in LLD. The study is longitudinal; after an initial assessment subject are followed for 2 ½ years. ADNI-D is committed to rapid data sharing of the ADNI-D data. This session will present initial data from the ADNI-Depression Study baseline evaluation and will be organized into 4 topic areas. ADNI-D Methodology and Sample Characteristics (Nelson) The ADNI D sample is a well characterized sample of older adults with depression. The ADNI D methodology facilitates comparisons of this cohort of LLD participants with the larger ADNI study of non-depressed older adults with normal cognition, Mild Cognitive Impairment (MCI), and dementia in order to clarify neurobiological mechanisms contributing to cognitive impairment and accelerated cognitive decline. This session will be focused on describing the ADNI-D methodology for participant enrollment and data collection and to report ADNI D sample (n=121) characteristics for depression severity, lifetime history of depression and depression treatment, and functional impairment. Specifically, participant enrollment criteria and methods for the assessment of depression severity and lifetime history of depression and depression treatments will be summarized. Additionally, standardized methodology for collection of neuroimaging data, biomarkers, and data management will be presented. Cognitive Functioning in the ADNI Depression cohort (Morin). The clarification of types and severity of cognitive dysfunction in LLD remains a significant area of research. This session will focus on identifying the cognitive impairment rates of participants with LLD in the ADNI-D study at baseline, highlighting methodological considerations for matching subjects to ADNI participants on basis of cognitive functioning for biomarker analyses, and to assess the relationship of subjective cognitive complaints and ApoE status with objective measures cognitive performance. Association of Cortical Atrophy, White Matter Lesions, and Amyloid Accumulation with Cognition in Late Life Depression (Mackin) Cognitive impairment (CI) in LLD is often characterized by deficits of executive functioning (EF), memory, and language and LLD has been strongly linked to accelerated rates of cognitive decline in older adults. However, the causes of CI in LLD are not clear, in part due to limitations of previous work which have lacked comparisons to well characterized non-depressed older adults with CI caused by neurodegenerative diseases that are often concurrent with LLD, such as the early stages of Alzheimer's disease (AD) and cerebrovascular disease (CVD). The ADNI-D study will facilitate clarification of neurobiological mechanisms contributing to CI in LLD. This session will be focused on evaluating the impact of reduced cerebral blood flow (hypoperfusion), cortical atrophy, and amyloid deposition on CI in LLD in the context of previously documented relationships between CI and subcortical white matter abnormalities and genetic risk factors. Functional Network Level Pathophysiologic Abnormalities Associated with Late Life Depression (Tosun) Cognitive impairment, particularly in the domains of information processing speed, executive functioning, and memory, in LLD is consistent with neurobiological conceptualizations of LLD as being heavily mediated by extended neural networks comprised of the orbitofrontal, medial prefrontal, and cingulate cortices, and anatomical connections with the temporal and parietal lobes, and basal ganglia. By disturbing the normal function and dynamics of different brain networks, the pathophysiological mechanisms of LLD may generate different specific clinical symptoms. Therefore we examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in LLD and whether such biomarkers may act as predictors, moderators, and mediators of depressive symptoms. This might facilitate development of personalized treatments based on a better understanding of the pathophysiological mechanisms of late life depression.

Effects of Transcranial Direct Current Stimulation on Cognition in late life depression

Background: Cognitive deficits are highly prevalent in patients with late life depression (LLD) and are known to persist in spite of successful antidepressant treatment. Preclinical and clinical studies suggest that transcranial direct current stimulation (tDCS) may enhance cognition however its effects in patients with LLD are not known.

Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

BackgroundLate-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology. MethodsWe studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance. ResultsLLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ21 = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ21 > 20.14, p < .001), greater anhedonia (Wald χ21 = 7.02, p = .008) and fatigue (Wald χ21 = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ21 > 4.65, p < .031), executive function (Wald χ21 = 7.18, p = .007), and working memory (Wald χ21 > 4.29, p < .038). ConclusionsLLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.

S156. Cognitive Effects of Deep Transcranial Magnetic Stimulation for Late-Life Depression

Late-life depression (LLD) is a growing global public health issue due to demographic changes. LLD is associated with cognitive functioning impairment. Deep repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for depression in younger adults associated with improved cognition; however, the impact of deep rTMS on cognition in LLD has not been explored.

Apathy Mediates Cognitive Difficulties in Geriatric Depression

Cognitive impairment associated with late-life depression can persist after remission of mood symptoms. Apathy, a common symptom of late-life depression, often leads to worse clinical outcomes. We examined if severity of apathy mediates cognitive difficulties in a cohort of older adults with major depression. One hundred thirty-eight older adults with depression (54.4% female; mean [SD] age: 69.7 [7.4] years; mean [SD] education:15.6 [2.7] years) were recruited to participate in a treatment study, and only baseline data were analyzed. All participants received a comprehensive evaluation of depression, apathy, and cognition. We examined whether apathy mediated the relationship between depression and cognition, focusing our attention on memory and cognitive control. We then explored whether the mediation effects differed across women and men. Increased apathy was significantly associated with worse depression and lower performance in the cognitive control domain but not in memory. Higher depressive scores were significantly associated with worse cognitive control but not memory. Mediation analyses revealed a significant indirect effect on cognitive control by depression through increased apathy scores with the mediator accounting for 21% of the total effect. Stratifying by sex, we found that women exhibited a significant indirect effect, with the mediator accounting for 47% of the total effect, whereas there was no mediation by apathy in men. The findings imply that increased apathy mediates the relationship between cognition and depression. The identification of mediating effects may inform future treatment strategies and preventive interventions that can focus on decreasing apathy to improve cognition in late-life depression.

Associations between pro-inflammatory cytokines, learning, and memory in late-life depression and healthy aging.

Pro-inflammatory cytokines may play a role in learning and memory difficulties and may be exacerbated in late-life depression (LLD), where pro-inflammatory markers are already elevated because of aging and age-related vascular risk. Learning and memory, and pro-inflammatory cytokines-Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and Interleukin-6 (IL-6) were measured in 24 individuals with LLD and 34 healthy older adults (HOA). Hippocampal volumes were segmented using Freesurfer software. Pro-inflammatory cytokines were higher in LLD compared with HOA. Regression analyses demonstrated that educational level and right hippocampal volume significantly contributed to explaining the variance in learning. For memory performance, educational level, right hippocampal volume and a group-by-IL-6 interaction significantly contributed to the model. High levels of IL-6 impact cognition in LLD but not HOA. Results suggest that high levels of inflammation alone are not sufficient to account for cognitive difficulties, but may interact with other factors in at-risk populations like LLD, to contribute to memory difficulties. Copyright © 2017 John Wiley & Sons, Ltd.

Systematic Review of Cognitive Effects of Electroconvulsive Therapy in Late-Life Depression

Late-life depression (LLD) is known to negatively impact cognition even after remission of mood symptoms. Electroconvulsive therapy (ECT) and newer nonconvulsive electrical and magnetic brain stimulation interventions have been shown to have cognitive effects in patients with neuropsychiatric disorders. This review systematically assessed the effects of ECT on cognition in LLD. EMBASE, Ovid Medline, and PsycINFO were systematically searched through June 2015. The search was limited to publications from peer-reviewed journals in the English language. A total of 5,154 publications was identified; 318 were reviewed in full text, of which 39 publications related to ECT were included. We focused this review only on ECT because evidence on newer interventions was deemed insufficient for a systematic review. This literature suggests increased rates of interictal and postictal cognitive decline with ECT but no long-term (i.e., 6 months or longer) deleterious effects on cognition. Instead, long-term cognitive outcomes with ECT have been reported as either not changed or improved. This literature favors nondominant unilateral ECT over bilateral ECT for cognition. Published literature on brain stimulation interventions in LLD is mainly limited to ECT. This literature suggests that deleterious effects of ECT in LLD are limited and transient, with better cognitive outcomes with unilateral ECT. There is not enough evidence to fully characterize long-term deleterious effects of ECT or effects of newer brain stimulation techniques on cognition in LLD.

Association between physical frailty and cognition in late-life depression

IntroductionCognitive frailty has recently been defined as the co-occurrence of physical frailty and cognitive impairment. Late-life depression is associated with both physical frailty and cognitive impairment, especially processing speed and executive functioning.Aim and objectivesIn this study, we investigated the association between physical frailty and cognitive functioning in depressed older persons.MethodsIn a total of 378 patients (&gt; 60 years) with depression according to DSM-IV criteria and a MMSE score of 24 points or higher, the physical frailty phenotype as well as its individual criteria (weight loss, weakness, exhaustion, slowness, low activity) was studied. Cognitive functioning was examined in 4 domains: verbal memory, working memory, interference control, and processing speed.ResultsOf the 378 depressed patients (range 60–90 years; 66.1% women), 61 were classified as robust (no frailty criteria present), 214 as prefrail (1 or 2 frailty criteria present), and 103 as frail (&gt; 3 criteria). Linear regression analyses, adjusted for confounders, showed that the severity of physical frailty was associated with poorer verbal memory, slower processing speed, and decreased working memory, but not with changes in interference control.ConclusionIn late-life depression, physical frailty is associated with poorer cognitive functioning, although not consistently for executive functioning. Future studies should examine whether cognitive impairment in the presence of physical frailty belongs to cognitive frailty and is indeed an important concept to identify a specific subgroup of depressed older patients, who need multimodal treatment strategies integrating physical, cognitive, and psychological functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effect of the 2011 FDA Warning for Citalopram on EKG Monitoring, Antidepressant Prescriptions, and Health Care Utilization

Introduction: Late-life depression (LLD) is a serious public health problem with estimated prevalence ranging from 1.8-25 percent in selected groups. LLD is known to negatively impact cognition both acutely and at follow up, even after remission of mood symptoms with antidepressant medications. Up to 50% conversion rate to dementia has been reported during long term follow up of patients with LLD. Electroconvulsive therapy (ECT), the most efficacious treatment for LLD, can be associated with detrimental effects on cognition. Some studies have demonstrated a pro-cognitive effect of non-convulsive electrical and magnetic brain stimulation interventions among patients with dementia. Methods: We conducted a systematic review of peer-reviewed literature on the effect of ECT and other brain stimulation interventions on the nature and course of cognitive function in patients with LLD. Search included three databases (EMBASE, Ovid Medline, and PsycINFO) through Feb 2014 and included the references of retrieved publications. The search limited age to 65 and over, human, English language and peer-reviewed journals. Results: A total of 3,972 publications were identified; 294 were reviewed and 36 met the inclusion criteria: 34 publications pertaining to ECT and 2 pertaining to repeated transcranial magnetic stimulation (rTMS). The majority of these publications report some transient post-ictal and inter-ictal confusion associated with ECT but no long-term (i.e., 6 months or longer) deleterious effects on cognition. Instead, long-term cognitive outcomes with ECT have been reported as either not changed or improved. rTMS studies reported no acute changes in cognition. Conclusions: Published literature on brain stimulation interventions in LLD is mainly limited to ECT. This literature suggests that deleterious effects of ECT on cognition in older adults are limited and transient. There is not enough evidence to characterize the long-term deleterious effects of ECT on cognition in LLD or the effects of other brain stimulation techniques on cognition in LLD.

Cognition in Late-Life Depression: Treatment Considerations

Late life depression (LLD) frequently presents with cognitive impairment, and growing evidence suggests that these disease processes are "linked" in multiple ways. For some individuals, LLD may be a recurrence of a long-standing depressive illness, while for others it may be the leading symptom of a developing neuropathological disorder. Overall, studies investigating the relationship between treatment of LLD and improvement in cognitive functioning have yielded mixed results. Research suggests that a subset of individuals with LLD and cognitive dysfunction will experience an improvement in cognitive function after antidepressant treatment, though a significant proportion will continue to exhibit cognitive impairment following resolution of their depressive symptoms. From a treatment standpoint, it is critical to ensure that an individual's depressive symptoms have been treated to remission, measured by a standardized rating scale such as the Geriatric Depression Scale (GDS). SSRI or SNRI monotherapy is often effective, and may be enhanced by employing an evidence-based psychotherapy such as Problem Solving Therapy (PST) or Interpersonal Therapy (IPT), modified to accommodate cognitive impairments that may be present. With respect to specific treatment of cognitive dysfunction, cognitive augmentation or training strategies can be helpful for some patients, and may be explored in combination with treatment of the primary depressive episode. While the introduction of a cholinesterase inhibitor (e.g. donepezil) may be considered, the potential benefit (modest improvement in cognition and functioning) must be weighed against an increased risk for worsening or recurrent depression. Finally, lifestyle factors-such as aerobic exercise, follow-up with a primary care physician for management of co-morbid medical illnesses, and regular participation in stimulating activities (such as through a senior center)-are important and should be included as part of the overall treatment plan.