Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.

Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.

A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.

Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.

Older adults with major depressive disorder (N = 228, ages 65–91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning.

Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity.

Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.

Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD.

Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity.

Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p = .031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety.

Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.

Mild decline in independent functioning is a core diagnostic criterion for Mild Cognitive Impairment. Performance-based assessments have been considered the gold standard to identify subtle deficits in functioning. Existing assessments were largely designed using demographically homogenous samples (white, highly educated, middle class) and often assume tasks are performed similarly across populations. The current study aimed to validate the utility of the Performance Assessment of Self-Care Skills (PASS) in determining cognitive status in a sample of predominantly African American, low-income older adults.

Cognition and functional capacity were measured in n=245 older participants (aged 50+ years) who were recruited from a larger community study located in Pittsburgh, PA. Cognitive status was defined by a mean split on the Modified Mini Mental Status Examination (3MS) score (84/100). Participants above the cutoff were classified as unlikely cognitive impairment (UCI) and those below classified as potential cognitive impairment (PCI). Functional capacity was assessed using the number of cues provided on three PASS subtasks: shopping, medication management, and critical information retrieval (higher score = worse functioning). Self-reported cognitive and functional decline was assessed via the Everyday Cognition (ECog) questionnaire (higher score = greater decline). Generalized linear models compared performance scores between groups adjusting for literacy (WRAT3), age, and education. Receiver operating characteristic curve (ROC) analyses were run for select functional performance scores to assess their predictive ability in discriminating between PCI and UCI.

Compared to the UCI group (N = 179), the PCI group (N = 66) was older (68 vs. 65 years, p = 0.05), less educated (11 years vs. 12 years, p < 0.01), had lower WRAT3 z-scores (0.19 vs. -0.55, p < .01), and required more cues on the shopping (4.33 vs. 8.54, p < 0.01) and medication management PASS subtasks (2.74 vs. 6.56, p < .01). Both groups reported elevated levels of subjective cognitive complaints on the ECog (1.46 vs. 1.56, p = .09) and performed similarly on the critical information retrieval PASS subtask (0.25 vs 0.54, p = .06). When discerning between UCI and PCI groups, the PASS Shopping subtask had an optimal cut-off score of 4, sensitivity of 0.86, specificity of 0.47, positive predictive value (PPV) of 0.37, and area under the curve (AUC) of 0.71. PASS Medication Management had an optimal cut-off score of 3, sensitivity of 0.77, specificity of 0.56, PPV of 0.39, and AUC of 0.74.

Subjective functional decline and performance on the critical information retrieval subtask were not associated with cognitive groups. PASS shopping and medication management had moderately high AUCs, suggesting they can reliably distinguish between groups. However, both tasks also exhibited low PPVs, low levels of specificity, and high levels of sensitivity, making them strong “rule-out” tests but poor “rule-in” tests in this sample. Because accurate assessment of functioning is useful for MCI and critical to dementia diagnosis, it is imperative we understand how these tasks function across different populations. Future work should 1) validate measures of functional ability across different populations and 2) develop population-appropriate assessments for use in clinical and research settings.

Previous findings suggest that time setting errors (TSEs) in the Clock Drawing Test (CDT) may be related mainly to impairments in semantic and executive function. Recent attempts to dissociate the classic stimulus-bound error (setting the time to “10 to 11” instead of “10 past 11”) from other TSEs, did not support hypotheses regarding this error being primarily executive in nature or different from other time setting errors in terms of neurocognitive correlates. This study aimed to further investigate the cognitive correlates of stimulus-bound errors and other TSEs, in order to trace possible underlying cognitive deficits.

We examined cognitive test performance of participants with preliminary diagnoses associated with mild cognitive impairment. Among 490 participants, we identified clocks with stimulus-bound errors (n = 78), other TSEs (n = 41), other errors not related to time settings (n = 176), or errorless clocks (n = 195).

No differences were found on any dependent measure between the stimulus-bound and the other TSErs groups. Group comparisons suggested TSEs in general, to be associated with lower performance on various cognitive measures, especially on semantic and working memory measures. Regression analysis further highlighted semantic and verbal working memory difficulties as being the most prominent deficits associated with these errors.

TSEs in the CDT may indicate underlying deficits in semantic function and working memory. In addition, results support previous findings related to the diagnostic value of TSEs in detecting cognitive impairment.

Neuroprogressive models of the trajectory of cognitive dysfunction in patients with bipolar disorder (BD) have been proposed. However, few studies have explored the relationships among clinical characteristics of BD, cognitive dysfunction, and aging.

We conducted a cross-sectional analysis in euthymic participants with the MATRICS Cognitive Consensus Battery, the Trail Making Test B, the Stroop Test, and the Wechsler Test of Adult Reading. Age- and gender-equated control participants without a mental disorder [‘Healthy Controls’ – HC)] were assessed similarly. We compared cognitive performance both globally and in seven domains in four groups: younger BD (age ⩽49 years; n = 70), older BD (age ⩾50 years; n = 48), younger HC (n = 153), and older HC (n = 44). We also compared the BD and HC groups using age as a continuous measure. We controlled for relevant covariates and applied a Bonferroni correction.

Our results support both an early impairment (‘early hit’) model and an accelerated aging model: impairment in attention/vigilance, processing speed, and executive function/working memory were congruent with the accelerated aging hypothesis whereas impairment in verbal memory was congruent with an early impairment model. BD and HC participants exhibited similar age-related decline in reasoning/problem solving and visuospatial memory. There were no age- or diagnosis-related differences in social cognition.

Our findings support that different cognitive domains are affected differently by BD and aging. Longitudinal studies are needed to explore trajectories of cognitive performance in BD across the lifespan.

The purpose of this exploratory study was to describe associations between NIH Toolbox-Cognition Battery subtests and legacy measures of neurocognitive function in two samples with neurological conditions (stroke and sickle cell disease (SCD)).

This exploratory secondary analysis uses data from two studies that assessed cognition at one time point using the NIH Toolbox-Cognition Battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and subtests from the Delis-Kaplan Executive Functions System (DKEFS). People with stroke (n = 26) and SCD (n = 64) were included. Associations between the NIH Toolbox-Cognition Battery subtests and corresponding legacy measures were examined using linear correlations, Bland–Altman analysis, and Lin’s Concordance Correlation Coefficient.

Linear correlations and Lin’s Concordance Correlation Coefficient were poor to strong in both samples on NIH Toolbox-CB subtests: Flanker Inhibitory Control and Attention (r = .35 to .48, Lin CCC = .27 to .37), Pattern Comparison Processing Speed (r = .40 to .65, Lin CCC = .37 to .62), Picture Sequence Memory (r = .19 to .55, Lin CCC = .18 to .48), Dimensional Change Card Sort (r = .39 to .77, Lin CCC = .38 to .63), Fluid Cognition Composite (r = .88 to .90, Lin CCC = .60 to .79), and Total Cognition Composite (r = .64 to .83, Lin CCC = .60 to .78). Bland–Altman analyses demonstrated wide limits of agreement across all subtests (–3.17 to 3.78).

The NIH Toolbox-Cognition Battery subtests may behave similarly to legacy measures as an overall assessment of cognition across samples at risk for neurological impairment. Findings should be replicated across additional clinical samples.

To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.

Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed.

Community-based multi-centered study based in Toronto across 5 academic sites.

Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls.

We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores.

A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD.

This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.

Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.

Neuropsychological assessment data from 121 participants in the Alzheimer’s Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.

A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.

LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.

Late-life depression may increase the risk of incident dementia, in particular of Alzheimer's disease and vascular dementia.

To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer's disease and vascular dementia in individuals with late-life depression in population-based prospective studies.

A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer's disease and vascular dementia in older adults with late-life depression.

Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P< 0.001), Alzheimer's disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer's disease (P=0.03).

Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer's disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer's disease.

Generalised anxiety disorder (GAD) in older adults is associated with neuropsychological impairment.

We examined neuropsychological functioning in older adults with GAD in comparison with psychiatrically healthy older adults at baseline, and we examined changes following a 12-week placebo-controlled trial of escitalopram.

A total of 160 participants without dementia aged ⩾60 with current GAD and 37 individuals in a comparison group without psychiatric history underwent neuropsychological assessment. Of these, 129 participants with GAD were reassessed post-treatment (trial registration: NCT00105586).

The participants with GAD performed worse than the comparison group in information processing speed, working memory, inhibition, problem-solving (including concept formation and mental flexibility) and immediate and delayed memory. Neuropsychological functioning was correlated with everyday functioning. After treatment, those with low cognitive scores experienced working memory, delayed memory and visuospatial ability improvement and those who reported clinical improvement in anxiety exhibited improvement in the ability to engage inhibition and episodic recall. These improvements were modest and of similar magnitude in both treatment conditions.

Generalised anxiety disorder in older adults is associated with neuropsychological impairments, which are associated with functional impairment. Those with GAD who either have a low cognitive performance or report clinical improvement in anxiety post-treatment, show improvement in multiple cognitive domains. These findings underscore the importance of treatments that aid cognition as well as anxiety symptoms.