Implications of vascular depression for successful cognitive aging in HIV Disease.

Although older adults with HIV are at high risk for mild neurocognitive disorders, a subset experience successful cognitive aging (SCA). HIV is associated with an increased risk of vascular depression (VasDep), which can affect cognitive and daily functioning. The current study examined whether VasDep impedes SCA among older adults with HIV. 136 persons with HIV aged 50 years and older were classified as either SCA+ (n = 37) or SCA- (n = 99) based on a battery of demographically adjusted neurocognitive tests and self-reported cognitive symptoms. Participants were also stratified on the presence of vascular disease (e.g., hypertension) and current depression as determined by the Composite International Diagnostic Interview and the Depression/Dejection scale of the Profile of Mood States. A Cochran-Armitage test revealed a significant additive effect of vascular disease and depression on SCA in this sample of older adults with HIV (z = 4.13, p <.0001). Individuals with VasDep had the lowest frequency of SCA+ (0%), which differed significantly from the group with only vascular disease (30%, OR = 0.04, CI = 0.002,0.68)) and the group with neither vascular disease nor depression (47% OR = 0.02, CI = 0.33,0.001). Findings were not confounded by demographics, HIV disease severity, or other psychiatric and medical factors (ps > 0.05). These data suggest that presence of VasDep may be a barrier to SCA in older adults with HIV disease. Prospective, longitudinal studies with neuroimaging-based operationalizations of VasDep are needed to further clarify this risk factor's role in the maintenance of cognitive and brain health in persons with HIV disease.

A deep learning approach for mental health quality prediction using functional network connectivity and assessment data.

While one can characterize mental health using questionnaires, such tools do not provide direct insight into the underlying biology. By linking approaches that visualize brain activity to questionnaires in the context of individualized prediction, we can gain new insights into the biology and behavioral aspects of brain health. Resting-state fMRI (rs-fMRI) can be used to identify biomarkers of these conditions and study patterns of abnormal connectivity. In this work, we estimate mental health quality for individual participants using static functional network connectivity (sFNC) data from rs-fMRI. The deep learning model uses the sFNC data as input to predict four categories of mental health quality and visualize the neural patterns indicative of each group. We used guided gradient class activation maps (guided Grad-CAM) to identify the most discriminative sFNC patterns. The effectiveness of this model was validated using the UK Biobank dataset, in which we showed that our approach outperformed four alternative models by 4-18% accuracy. The proposed model's performance evaluation yielded a classification accuracy of 76%, 78%, 88%, and 98% for the excellent, good, fair, and poor mental health categories, with poor mental health accuracy being the highest. The findings show distinct sFNC patterns across each group. The patterns associated with excellent mental health consist of the cerebellar-subcortical regions, whereas the most prominent areas in the poor mental health category are in the sensorimotor and visual domains. Thus the combination of rs-fMRI and deep learning opens a promising path for developing a comprehensive framework to evaluate and measure mental health. Moreover, this approach had the potential to guide the development of personalized interventions and enable the monitoring of treatment response. Overall this highlights the crucial role of advanced imaging modalities and deep learning algorithms in advancing our understanding and management of mental health.

Depression, Vascular Burden, and Dementia Prevalence in Late Middle-Aged and Older Black Adults.

OBJECTIVES: Late-life depression and white matter hyperintensities (WMH) have been linked to increased dementia risk. However, there is a dearth of literature examining these relationships in Black adults. We investigated whether depression or WMH volume are associated with a higher likelihood of dementia diagnosis in a sample of late middle-aged to older Black adults, and whether dementia prevalence is highest in individuals with both depression and higher WMH volume. METHODS: Secondary data analysis involved 443 Black participants aged 55+ with brain imaging within 1 year of baseline visit in the National Alzheimer's Coordinating Center Uniform Data Set. Chi-square analyses and logistic regression models controlling for demographic variables examined whether active depression in the past 2 years, WMH volume, or their combination were associated with higher odds of all-cause dementia. RESULTS: Depression and higher WMH volume were associated with a higher prevalence of dementia. These associations remained after controlling for demographic factors, as well as vascular disease burden. Dementia risk was highest in the depression/high WMH volume group compared to the depression-only group, high WMH volume-only group, and the no depression/low WMH volume group. Post hoc analyses comparing the Black sample to a demographically matched non-Hispanic White sample showed associations of depression and the combination of depression and higher WMH burden with dementia were greater in Black compared to non-Hispanic White individuals. DISCUSSION: Results suggest late-life depression and WMH have independent and joint relationships with dementia and that Black individuals may be particularly at risk due to these factors.

Association of white matter hyperintensities and clinical vascular burden with depressive symptoms in Black older adults.

OBJECTIVES: Black older adults have a higher vascular burden compared to non-Hispanic White (NHW) older adults, which may put them at risk for a form of depression known as vascular depression (VaDep). The literature examining VaDep in Black older adults is sparse. The current study addressed this important gap by examining whether vascular burden was associated with depressive symptoms in Black older adults. METHODS: Participants included 113 Black older adults from the Healthy Brain Project, a substudy of the Health, Aging, and Body Composition Study. In multiple regression analyses, clinical vascular burden (sum of vascular conditions) and white matter hyperintensity (WMH) volume predicted depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale, controlling for demographic variables. Follow-up analyses compared the associations in the Black subsample and in 179 NHW older adults. RESULTS: Higher total WMH volume, but not clinically-defined vascular burden, predicted higher concurrent depressive symptoms and higher average depressive symptoms over 4 years. Similar associations were found between uncinate fasciculus (UF) WMHs and concurrent depressive symptoms and between superior longitudinal fasciculus WMHs and average depressive symptoms. The association between depressive symptoms and UF WMH was stronger in Black compared to NHW individuals. CONCLUSION: This research is consistent with the VaDep hypothesis and extends it to Black older adults, a group that has historically been underrepresented in the literature. Results highlight WMH in the UF as particularly relevant to depressive symptoms in Black older adults and suggest this group may be particularly vulnerable to the negative effects of WMH.

Consensus Paper: Cerebellum and Ageing.

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

Key Findings from Mental Health Research During the Menopause Transition for Racially and Ethnically Minoritized Women Living in the United States: A Scoping Review.

Background: Racially and ethnically minoritized (REM) women experience social and structural factors that may affect their response to mental health treatment and menopausal symptoms during the menopause transition (MT). This scoping review on mental health during the MT for REM women in the United States was conducted to characterize factors associated with mental health challenges. Materials and Methods: Five databases were searched. Articles were included if focused on MT in REM women in the United States and its territories with specific mental illnesses and published in English from 2005 to 2021. Titles and abstracts and full text were screened. Screening and data collection were completed in duplicate by two reviewers in Covidence. Results: Sixty-five articles were included and indicate that REM women experience a disproportionate burden of depressive symptoms during the MT. Less evidence is reported about anxiety, Post-Traumatic Stress Disorder, psychosis, schizophrenia, and other mental illnesses. The risk factors associated with mental illness during MT are social, structural, and biological. Treatment response to therapeutic interventions is often underpowered to explain REM differences. Conclusion: Depression during the MT is associated with negative outcomes that may impact REM women differentially. Incorporating theoretical frameworks (e.g., intersectionality, weathering) into mental health research will reduce the likelihood that scientists mislabel race as the cause of these inequities, when racism and intersecting systems of oppression are the root causes of differential expression of mental illness among REM women during the MT. There is a need for interdisciplinary research to advance the mental health of REM women.

Implications of Vascular Depression for Successful Cognitive Aging in HIV disease.

Introduction: Although older adults with HIV are at high risk for mild neurocognitive disorders, a subset experience successful cognitive aging (SCA). HIV is associated with an increased risk of vascular depression (VasDep), which can affect cognitive and daily functioning. The current study examined whether VasDep impedes SCA among older adults with HIV. Methods: 136 persons with HIV aged 50 years and older were classified as either SCA+ (n=37) or SCA- (n=99) based on a battery of demographically adjusted neurocognitive tests and self-reported cognitive symptoms. Participants were also stratified on the presence of vascular disease (e.g., hypertension) and current depression as determined by the Composite International Diagnostic Interview and the Depression/Dejection scale of the Profile of Mood States. Results: A Cochran-Armitage test revealed a significant additive effect of vascular disease and depression on SCA in this sample of older adults with HIV (z=4.13, p<.0001). Individuals with VasDep had the lowest frequency of SCA+ (0%), which differed significantly from the group with only vascular disease (30%, OR=0.04, CI=0.002,0.68)) and the group with neither vascular disease nor depression (47% OR =0.02, CI=0.33,0.001). Findings were not confounded by demographics, HIV disease severity, or other psychiatric and medical factors (ps>.05). Discussion: These data suggest that presence of VasDep may be a barrier to SCA in older adults with HIV disease. Prospective, longitudinal studies with neuroimaging-based operationalizations of VasDep are needed to further clarify this risk factor's role in the maintenance of cognitive and brain health in persons with HIV disease.

Intersectionality in Alzheimer's Disease: The Role of Female Sex and Black American Race in the Development and Prevalence of Alzheimer's Disease.

It is well known that vascular factors and specific social determinants of health contribute to dementia risk and that the prevalence of these risk factors differs according to race and sex. In this review, we discuss the intersection of sex and race, particularly female sex and Black American race. Women, particularly Black women, have been underrepresented in Alzheimer's disease clinical trials and research. However, in recent years, the number of women participating in clinical research has steadily increased. A greater prevalence of vascular risk factors such as hypertension and type 2 diabetes, coupled with unique social and environmental pressures, puts Black American women particularly at risk for the development of Alzheimer's disease and related dementias. Female sex hormones and the use of hormonal birth control may offer some protective benefits, but results are mixed, and studies do not consistently report the demographics of their samples. We argue that as a research community, greater efforts should be made to not only recruit this vulnerable population, but also report the demographic makeup of samples in research to better target those at greatest risk for the disease.

Distinct latent symptom profiles in late-onset depressive symptoms in community-dwelling older adults.

OBJECTIVES: To examine the symptom profiles of late-onset depressive symptoms in a sample of older adults. METHOD: The sample included 1,192 participants from the National Alzheimer's Coordinating Center Data Set. Participants were ≥65 years old, community-dwelling, and without cognitive impairment or a prior history of depression. Depressive symptoms were assessed using the Geriatric Depression Scale, 15-item (GDS-15). Latent class analysis (LCA) was used to identify and group participants based on profiles of depressive symptoms. RESULTS: LCA revealed three distinct symptom profiles: (1) an Anhedonia/Amotivation profile with a higher probability of endorsing a combination of low positive emotion and amotivation (6%), (2) an Amotivation/Withdrawal profile with a high probability of endorsing only amotivational depressive symptoms (35%), and (3) an asymptomatic profile with no probability of endorsing any depressive symptoms (59%). Amotivational depressive symptoms were observed across both symptomatic profiles, while depressed mood (e.g. sadness) did not predominantly characterize any profile in this sample. There were also significant differences among symptom profiles in terms of demographic and clinical characteristics. CONCLUSIONS: Findings highlight the importance of understanding depression at the symptom pattern level. A profile-based diagnostic approach may help improve the recognition of depressive symptoms in older adults.

Rostral anterior cingulate connectivity in older adults with subthreshold depressive symptoms: A preliminary study.

Subthreshold depressive symptoms are highly prevalent among older adults and are associated with numerous health risks including cognitive decline and decreased physical health. One brain region central to neuroanatomical models of depressive disorders is the anterior cingulate cortex (ACC). The rostral portion of the ACC-comprised of the pregenual ACC and subgenual ACC-is implicated in emotion control and reward processing. The goal of the current study was to examine how functional connectivity in subregions of the rostral ACC relate to depressive symptoms, measured by the Beck Depression Inventory-Second Edition, in an ethnically diverse sample of 28 community-dwelling older adults. Based on meta-analyses of previous studies in primarily young adults with clinical depression, we hypothesized that greater depressive symptoms would be associated with primarily increased resting-state functional connectivity from both the subgenual ACC and pregenual ACC to default mode network regions and the dorsolateral PFC. We instead found that higher depressive symptoms were associated with lower functional connectivity of the ACC to the dorsolateral PFC and regions within the default mode network, including from the subgenual ACC to the dorsolateral PFC and anterior cingulate and from the pregenual ACC to the middle cingulate gyrus. This preliminary study highlights brain alterations at subthreshold levels of depressive symptoms in older adults, which could serve as targets for interventions.

Elevated frequency and everyday functioning implications of vascular depression in persons with HIV disease.

Depression and cardiovascular disease are common and associated with one another in HIV disease. This study aimed to determine the frequency and everyday functioning implications of the clinical syndrome of vascular depression among people living with HIV (PLWH). Participants in this cross-sectional study included 536 PLWH and 272 seronegative individuals who completed a biomedical and psychiatric research evaluation. Vascular depression was operationalized as the current presence of: 1) two or more vascular conditions; and 2) depression as determined by a normative elevation on the Depression/Dejection subscale of the Profile of Mood States or a diagnosis of Major Depressive Disorder per the Composite International Diagnostic Interview. Everyday functioning was measured by both self- and clinician-rated activities of daily living. A logistic regression model showed that HIV was associated with a three-fold increased risk of vascular depression, independent of potential confounding factors. A second logistic regression model within the PLWH sample showed that PLWH with vascular depression had significantly greater odds of dependence in everyday functioning as compared to PLWH with either vascular disease or depression alone. The elevated frequency of vascular depression in PLWH is consistent with the vascular depression hypothesis from the late-life depression literature. The high rate of functional dependence among PLWH with vascular depression highlights the clinical importance of prospective work on this syndrome in the context of HIV disease.

Impact of cardiovascular risk factors on the relationships of physical activity with mood and cognitive function in a diverse sample.

Physical activity has well-known benefits for older adults' mood and cognitive functioning; however, it is not clear whether risk factors for cardiovascular disease (CVD) affect the relationships of physical activity with these health outcomes among diverse older adults. This study investigated the impact of CVD risk burden on the relationships among self-reported physical activity, mood, and cognitive functioning in a diverse sample of 62 adults age 45 and older. We found that higher physical activity was associated with better attention and verbal working memory at lower CVD risk, but with worse attention and verbal working memory at higher CVD risk levels. Thus, higher CVD risk might limit the effectiveness of exercise interventions for mood and cognitive functioning. Future studies are needed to further clarify individual differences that impact the relationships among physical activity, CVD risk, and cognitive outcomes.

Incidence of post-stroke depression symptoms and potential risk factors in adults with aphasia in a comprehensive stroke center.

INTRODUCTION: Depression may be a frequent sequela after stroke, however, its incidence has rarely been reported. The likelihood of post-stroke depression (PSD) may relate to individual factors including the presence of aphasia, which also complicates PSD diagnosis. The current study's purpose was to investigate the incidence of PSD symptoms in adults with aphasia, compare it to the incidence of PSD symptoms in adults without aphasia, and to identify potential risk factors for developing PSD in adults with aphasia. METHOD: Incidence proportions and relative risk were calculated using data compiled from 970 patient records at an urban tertiary care academic institution and comprehensive stroke center throughout the year of 2019. Focusing exclusively on adults with aphasia, the selected variables of age, gender, race, and aphasia severity were used to conduct logistic regression analyses to explore potential risk factors contributing to the development of PSD. RESULTS: Adults with aphasia were 7.408 times more likely to exhibit PSD symptoms than adults without aphasia. Logistic regression controlling for the presence of aphasia showed a significant relationship between aphasia severity and post-stroke depression symptoms. Adults with aphasia were 2.06 times more likely to experience post-stroke depression symptoms with every 1-point increase in aphasia severity. CONCLUSIONS: These findings align with earlier evidence identifying aphasia as a risk factor for experiencing PSD symptoms and also suggest aphasia severity is proportionate to the risk. This highlights the need for early identification of PSD symptoms in persons with aphasia in order to provide timely interventions.

Vascular depression in Black Americans: A systematic review of the construct and its cognitive, functional, and psychosocial correlates.

Objective: Vascular burden is associated with cognitive deficits and a form of late-life depression, vascular depression (VaDep), which is marked by decreased white matter integrity, executive dysfunction, poor treatment response, and functional disability. Older Black Americans represent a vulnerable population at risk of developing VaDep, but the literature in this group is limited. Thus, the goal of this systematic review is to summarize the existing literature that informs our understanding of VaDep in older Black Americans, including cognitive, functional, and psychosocial outcomes. Method: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, studies were identified that examined the relationship between vascular disease or vascular risk factors and that either had a sample of at least 75% Black participants or conducted race-specific analyses. Thirty studies met all inclusion criterion based on review of both authors. Results: Overall, studies support the construct of VaDep in older Black Americans. There is preliminary support for VaDep-related cognitive and functional deficits, and mixed findings regarding racial disparities in prevalence of VaDep. Conclusion: This review underscores the need for further neuroimaging and neuropsychological research in Black older adults with comorbid depression and vascular disease. Findings also highlight the importance of screening for depressive symptoms in Black individuals with multiple vascular risk factors.

Subthreshold depressive symptoms relate to cuneus structure: Thickness asymmetry and sex differences.

Despite the prominence of frontolimbic regions in depression research, recent studies also implicate posterior brain regions, including the cuneus. The current study examined the relationship between depressive symptoms and asymmetry in cuneal cortical thickness in healthy adults between the ages of 18 and 81 with primarily subthreshold levels of depressive symptoms. An asymmetry index was calculated for cortical thickness in the cuneus [(left - right) × 100/(left + right)], and regression analyses were conducted with total scores on the Center for Epidemiologic Studies Depression Scale predicting this asymmetry index, controlling for age and sex. Higher depressive symptoms were associated with a left > right asymmetry in cuneal cortical thickness, reflecting greater cortical thickness in the left hemisphere compared to right hemisphere. Follow-up analyses examining CES-D subscales showed significant effects for somatic symptoms of depression, but not negative affect or anhedonia. Analyses stratified by sex yielded significant effects in men but not in women. Results of this preliminary study further support the cuneus' role in depression and highlight the importance of examining symptom dimensions and sex differences in the neurobiology of depression.

Clinical Neuropsychological Evaluation in Older Adults With Major Depressive Disorder.

PURPOSE OF THE REVIEW: Older adults with major depressive disorder are particularly vulnerable to MDD-associated adverse cognitive effects including slowed processing speed, decreased attention, and executive dysfunction. The purpose of this review is to describe the approach to a clinical neuropsychological evaluation in older adults with MDD. Specifically, this review compares and contrasts neurocognitive screening and clinical neuropsychological evaluation procedures and details the multiple components of the clinical neuropsychological evaluation. RECENT FINDINGS: Research has shown that neurocognitive screening serves a useful purpose to provide an acute and rapid assessment of global cognitive function; however, it has limited sensitivity and specificity. The clinical neuropsychological evaluation process is multifaceted and encompasses a review of available medical records, neurobehavioral status and diagnostic interview, comprehensive cognitive and clinical assessment, examination of inclusion and diversity factors as well as symptom and performance validity, and therapeutic feedback. As such, the evaluation provides invaluable information on multiple cognitive functions, establishes brain and behavior relationships, clarifies neuropsychiatric diagnoses, and can inform the etiology of cognitive impairment. Clinical neuropsychological evaluation plays a unique and critical role in integrated healthcare for older adults with MDD. Indeed, the evaluation can serve as a nexus to synthesize information across healthcare providers in order to maximize measurement-based care that can optimize personalized medicine and overall health outcomes.

Orbitofrontal and Cingulate Thickness Asymmetry Associated with Depressive Symptom Dimensions.

Both clinical depression and subthreshold depressive symptoms have been associated with alterations in cortical thickness. Studies have yielded conflicting results regarding whether cortical thinning or cortical thickening best characterize the depressive state. Also unclear is whether cortical thickness differences are lateralized. This study examined the relationship between depressive symptom dimensions and cortical thickness asymmetry in cingulate and orbitofrontal regions. Fifty-four community-dwelling adults between the ages of 18 and 81 years received a 3-Tesla magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Cortical thickness values were extracted for the rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, isthmus cingulate, and orbitofrontal cortex. An asymmetry index was calculated for each region. Data were analyzed using separate general linear models for each region, in which the CES-D somatic symptoms, negative affect, and anhedonia subscale scores predicted the asymmetry indices, controlling for age and sex. Higher scores on the anhedonia subscale were associated with right-sided asymmetry in orbitofrontal thickness, whereas higher somatic symptom subscale scores predicted greater left-sided asymmetry in posterior cingulate thickness. Follow-up analyses showed the orbitofrontal effect was specific to the medial, not the lateral, orbitofrontal cortex. These results suggest asymmetries in cortical thickness are apparent at even subthreshold levels of depressive symptoms, as all but five participants were below the CES-D cutoff for clinical depression, and that the relationship varies for different symptom dimensions of depression. Understanding brain asymmetries across the range of depressive symptom severity is important for informing targeted depression treatment.

Be Fit, Be Sharp, Be Well: The Case for Exercise as a Treatment for Cognitive Impairment in Late-life Depression.

OBJECTIVE: To lay out the argument that exercise impacts neurobiological targets common to both mood and cognitive functioning, and thus more research should be conducted on its use as an alternative or adjunctive treatment for cognitive impairment in late-life depression (LLD). METHOD: This narrative review summarizes the literature on cognitive impairment in LLD, describes the structural and functional brain changes and neurochemical changes that are linked to both cognitive impairment and mood disruption, and explains how exercise targets these same neurobiological changes and can thus provide an alternative or adjunctive treatment for cognitive impairment in LLD. RESULTS: Cognitive impairment is common in LLD and predicts recurrence of depression, poor response to antidepressant treatment, and overall disability. Traditional depression treatment with medication, psychotherapy, or both, is not effective in fully reversing cognitive impairment for most depressed older adults. Physical exercise is an ideal treatment candidate based on evidence that it 1) is an effective treatment for depression, 2) enhances cognitive functioning in normal aging and in other patient populations, and 3) targets many of the neurobiological mechanisms that underlie mood and cognitive functioning. Results of the limited existing clinical trials of exercise for cognitive impairment in depression are mixed but overall support this contention. CONCLUSIONS: Although limited, existing evidence suggests exercise may be a viable alternative or adjunctive treatment to address cognitive impairment in LLD, and thus more research in this area is warranted. Moving forward, additional research is needed in large, diverse samples to translate the growing research findings into clinical practice.

Depression and episodic memory across the adult lifespan: A meta-analytic review.

Episodic memory deficits have increasingly been recognized as a cognitive feature of depression. To quantify these deficits and determine how they are moderated by various tasks (e.g., stimulus valence) and participant (e.g., age, depression diagnosis) variables, we conducted a three-level meta-analysis on 995 effect sizes derived from 205 studies with 236 unique comparisons between depressive and control groups on episodic memory measures. Overall, depression was associated with small to moderate deficits in episodic memory, Hedges' g = -0.36, 95% CI [-0.41 to -0.31]. Effects were larger in older age, in diagnosed compared to subthreshold depression, and in those taking medication for depression; effects did not differ between those with current and remitted symptoms. Stimulus valence moderated the effects, such that depression-related deficits were particularly pronounced for positive and neutral stimuli, but not for negative stimuli. Educational attainment served as a sort of protective factor, in that at higher levels of education, depressed group performance was more similar to that of controls. These findings confirm the episodic memory deficits in depression but highlight the important differences in the size of these deficits across a number of task- and participant-related variables. (PsycInfo Database Record (c) 2022 APA, all rights reserved).