White Noise-Is Anxiety in Late-Life Associated With White Matter Hyperintensity Burden?

OBJECTIVE: We investigated the relationship between anxiety phenotypes (global anxiety, worry, and rumination) and white matter hyperintensities (WMH), with special consideration for the roles of age and executive function (EF). Our hypotheses were 1) anxiety phenotypes would be associated with WMH and 2) EF would moderate this relationship. DESIGN: Cross-sectional. SETTING: Participants were recruited from the local community (Pittsburgh, PA). PARTICIPANTS: We recruited 110 older adults (age ≥ 50) with varying worry severity and clinical comorbidity. INTERVENTIONS: Not applicable. MEASUREMENTS: Demographics (age, sex, race, education), clinical measures (cumulative illness burden, global anxiety, worry, and rumination), EF, and WMH quantified with magnetic resonance imaging. RESULTS: Lower global anxiety and worry severity were significantly correlated with higher WMH volume, though the global anxiety relationship was not significant after controlling for age. Rumination as not associated with WMH burden. EF was not correlated with either global anxiety, worry, rumination, or WMH. However, in those with advanced age and/or greater WMH burden, there was an association between worry and EF as well as EF and WMH. CONCLUSION: Longitudinal studies are needed in order to clarify the complex interactions between anxiety phenotypes, WMH, and EF.

"And Does That Necessarily Mean Absolutely Alzheimer's?" An Analysis of Questions Raised Following Amyloid PET Results Disclosure.

INTRODUCTION: Amyloid PET scans provide individuals with mild cognitive impairment (MCI) information about their risk of progressing to Alzheimer's dementia (AD). Given the wide-ranging implications of this information, best practice guidelines are needed to support researchers and clinicians disclosing these high-stakes test results. To inform the development of such guidelines, this analysis aims to describe questions and concerns raised during the disclosure of amyloid PET results in the context of MCI. METHODS: Qualitative description was performed to analyze (n = 34) transcripts of audio-recorded amyloid PET results disclosure sessions involving MCI care dyads. The analysis focused on characterizing the frequency and nature of questions raised during an open question-and-answer (Q&A) period following the return of scan results using a standardized protocol. RESULTS: Nearly all (n = 32/34) dyads posed questions during Q&A. Questions fell within six main categories with the most common being requests for clarification regarding AD/MCI, and next steps given the result. Questions were interspersed with comments reflecting the need for emotional support. Independently administered assessments of comprehension of results showed that, following the disclosure and Q&A, 31/32 participants with MCI and 31/31 care partners scored ≥4 on a 5-point scale. The number of questions asked by care partners during Q&A positively correlated with their level of comprehension (n = 31, Spearman's r = 0.370, p = 0.040). DISCUSSION: This analysis highlights the value of providing opportunities for patients and their family members to ask questions upon learning patients' brain amyloid status. Disclosing clinicians should be prepared to provide clarification, resources, and support to patients and families during the return of amyloid PET results.

Heterogeneity of Cognition in Older Adults with Remitted Major Depressive Disorder: A Latent Profile Analysis.

OBJECTIVES: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. DESIGN: Secondary cross-sectional analysis using latent profile analysis. SETTING: Multisite clinical trial in Toronto, Canada. PARTICIPANTS: One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). MEASUREMENTS: Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. RESULTS: We identified three latent profiles: Profile 1 (poor cognition; n = 75, 42.1%), Profile 2 (intermediate cognition; n = 75, 42.1%), and Profile 3 (normal cognition; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. CONCLUSION: Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups.

Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability.

OBJECTIVES: 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 (Aß) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. PARTICIPANTS AND MEASUREMENTS: 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 Aß 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. RESULTS: Greater anxiety severity was associated with lower OFC volume (ß = -68.25, t = -2.18, p = .031) and greater cognitive dysfunction (ß = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aß SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (ß = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety. CONCLUSIONS: 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.

A cross-sectional study of cognitive performance in bipolar disorder across the lifespan: the cog-BD project.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

OBJECTIVE: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. METHODS: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. RESULTS: Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase. CONCLUSION: This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine.

OBJECTIVE: In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance. DESIGN: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals. RESULTS: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression. CONCLUSION: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.

Validation of the NIH Toolbox-Cognition Battery against legacy neurocognitive measures in adults with cognitive impairments: An exploratory analysis.

OBJECTIVE: 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)). METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

About time: neurocognitive correlates of stimulus-bound and other time setting errors in the Clock Drawing Test.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Change in patient-centered outcomes of psychological well-being, sleep, and suicidality following treatment with intravenous ketamine for late-life treatment-resistant depression.

OBJECTIVE: To examine whether psychological well-being, sleep, and suicidality improved with treatment with intravenous (IV) ketamine for late-life treatment-resistant depression (TRD). METHODS: This is an analysis of secondary outcomes in an open-label late-life TRD study examining the safety, tolerability, and feasibility of IV ketamine infusions. In the acute phase, participants (N = 25) aged 60 years or older received twice-a-week IV ketamine for 4 weeks. Then, participants with Montgomery-Asberg Depression Rating Scale (MADRS) total score <10 or ≥ 30% reduction from baseline proceeded to the continuation phase, an additional four weeks of once-a-week IV ketamine. The secondary outcomes analyzed here are based on the National Institute of Health Toolbox Psychological Well-Being subscales for Positive Affect and General Life Satisfaction, the Pittsburgh Sleep Quality Index, and the Scale for Suicidal Ideation. RESULTS: Psychological well-being, sleep, and suicidality improved during the acute phase and those improvements were sustained during the continuation phase. Greater improvements in measures of psychological well-being and sleep were seen in participants who had greater improvements in MADRS scores and moved onto the continuation phase. All but one of the few participants with high suicidality at baseline improved; there were no cases of treatment-emergent suicidality. CONCLUSIONS: Psychological well-being, sleep, and suicidality improved in participants with late-life TRD who received IV ketamine for 8 weeks. A future larger and longer controlled trial is needed to confirm and extend these findings. REGISTRATION: ClinicalTrials.gov identifier: NCT04504175.

Postoperative delirium in older patients after undergoing pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: To determine the 7-day incidence and risk factors of postoperative delirium (POD) occurring after prolapse surgery in women aged ≥60 years. METHODS: A prospective study of women ≥60 years undergoing prolapse surgery at a large academic center. The primary outcome is positive Confusion Assessment Method delirium screen administered in person or by telephone at the time of hospital discharge and postoperative days 1, 3, 5, and 7. RESULTS: This analysis included 165 patients, mean ± SD age of 72.5 ± 6.1 years, with median (IQR) years of education of 13 (12-16), and baseline Modified Mini-Mental Status (3MS) Exam score of 95 (92-98). Prolapse repair type was vaginal for 70% (n=115) and laparoscopic for 30% (n=50) of patients; most under general anesthesia, 151 (92.1%). The incidence of positive delirium screen during the first week after surgery was 12.1% (n=20). Most of these participants screened positive on postoperative day 0, 8.4% (n=14). In univariate analyses, a positive screen was associated with older age and fewer education years, lower 3MS exam score, greater baseline geriatric depression scale score, and greater frailty score. Lower 3MS score was the only variable that remained significant in the final model (adjusted odds ratio 0.84, 95% CI 0.75-0.95). CONCLUSIONS: One in 12 women ≥60 years deemed eligible for discharge on the day of prolapse surgery screens positive for delirium. The 7-day POD incidence is comparable to other elective non-cardiac surgery cohorts. Given the increasing trend toward same day discharge after major prolapse surgery, more research is needed to determine the impact of universal delirium screening as part of discharge assessments.

Design of the think PHRESH longitudinal cohort study: Neighborhood disadvantage, cognitive aging, and alzheimer's disease risk in disinvested, black neighborhoods.

BACKGROUND: Black Americans have disproportionately higher rates and earlier onset of Alzheimer's disease and related dementias (ADRD) relative to White Americans. We currently lack a comprehensive understanding of how the lived experience and broader societal factors, including cumulative exposure to structural racism and the mechanisms underlying the risks, may contribute to elevated ADRD risk in Black Americans. METHODS: The Think PHRESH study builds on existing, community-based research infrastructure, from the ongoing Pittsburgh Hill/Homewood Research on Neighborhood Change and Health (PHRESH) studies, to examine the contributions of dynamic neighborhood socioeconomic conditions across the lifecourse to cognitive outcomes in mid- and late-life adults living in two historically disinvested, predominantly Black communities (anticipated n = 1133). This longitudinal, mixed-methods study rests on the premise that neighborhood racial segregation and subsequent disinvestment contributes to poor cognitive outcomes via factors including (a) low access to educational opportunities and (b) high exposure to race- and socioeconomically-relevant stressors, such as discrimination, trauma, and adverse childhood events. In turn, these cumulative exposures foster psychological vigilance in residents, leading to cardiometabolic dysregulation and sleep disruption, which may mediate associations between neighborhood disadvantage and ADRD risk. This premise recognizes the importance of potential protective factors that may promote cognitive health, including neighborhood social cohesion, safety, and satisfaction. The proposed study will leverage our existing longitudinal data on risk/protective factors and biobehavioral mediators and will include: (1) up to three waves of cognitive assessments in participants ages 50 years + and one assessment in participants ages 35-49 years; clinical adjudication of ADRD will be completed in participants who are 50+, (2) extensive surveys of risk and protective factors, (3) two assessments of blood pressure and objectively measured sleep, (4) a comprehensive assessment of life and residential history; and (5) two rounds of in-depth qualitative interviews to reveal lifecourse opportunities and barriers experienced by Black Americans in achieving optimal cognitive health in late life. DISCUSSION: Understanding how structural racism has influenced the lived experience of Black Americans, including dynamic changes in neighborhood conditions over time, is critical to inform multi-level intervention and policy efforts to reduce pervasive racial and socioeconomic disparities in ADRD.

Diagnostic Precision in the Detection of Mild Cognitive Impairment: A Comparison of Two Approaches.

OBJECTIVE: This study compared diagnostic rates and clinical predictors of discrepancies between diagnoses conferred via: 1) a comprehensive neuropsychological evaluation and National Institute on Aging-Alzheimer's Association (NIA-AA) criteria versus 2) a cognitive screener and Diagnostic Statistical Manual of Mental Disorders (DSM-5) criteria. DESIGN: Cross-sectional examination of baseline data from the Prevention of Alzheimer's dementia (AD) using Cognitive remediation and transcranial direct current stimulation in Mild Cognitive Impairment (MCI) and Depression (PACt-MD; ClinicalTrials.gov Identifier: NCT02386670) trial. SETTING: Five geriatric psychiatry and memory clinics located at academic hospitals affiliated with the Department of Psychiatry, University of Toronto. PARTICIPANTS: Older adults (N = 431) with a history of major depressive disorder (MDD) in remission, MCI, or both. MEASUREMENTS: Main outcome was a comparison of NIA-AA diagnostic rates of MCI or dementia versus DSM-5 rates of mild or major neurocognitive disorder. Secondary analyses examined demographic, race, gender, premorbid intellectual ability, psychosocial, health-related, and genetic predictors of discrepancy between DSM-5 and NIA-AA diagnoses. RESULTS: There were 103 (23.8%) discrepant cases, with most (91; 88.3%) of these discrepant cases reflecting more impairment with the detailed neuropsychological testing and NIA-AA criteria. Discrepancies were more likely in individuals with a history of MDD or who had at least one ApoE4 allele. CONCLUSION: The NIA-AA criteria, in conjunction with comprehensive neuropsychological testing, identified a greater prevalence of cognitive impairment than DSM-5 criteria, in conjunction with the Montreal Cognitive Assessment. Detailed neuropsychological evaluations are recommended for older adults who have a history of MDD or a genetic vulnerability to dementia.

Comparing cardiovascular risk factors in older persons with mild cognitive impairment and lifetime history of major depressive disorder.

OBJECTIVES: 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. DESIGN: 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. SETTING: Community-based multi-centered study based in Toronto across 5 academic sites. PARTICIPANTS: Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls. MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Late-Onset Suicide: A Dementia Prodrome?

OBJECTIVES: This study examined whether late-onset (versus early-onset) suicidal behavior is associated with worse cognition. METHODS: Participants included 278 adults aged 50+ years (56 nonpsychiatric comparison group; 67 nonsuicidal depressed older adults; 63 depressed suicide ideators; and 44 late-onset (55+ years) and 48 early-onset suicide attempters (<55 years). Using a case-control design, this study examined group differences in global cognition, episodic memory, information processing speed, and executive functioning, assessed using the Repeatable Battery of Neuropsychological Status and the Trail Making Test from the Delis-Kaplan Executive Function System. Linear regression was used for data analyses. RESULTS: Both attempter groups displayed worse executive functioning than nonsuicidal depressed older adults. Late-onset attempters additionally displayed poorer global cognition and processing speed than nonsuicidal depressed older adults and poorer memory than early-onset attempters. CONCLUSIONS: Late-onset suicidal behavior is associated with worse performance in a broad range of cognitive domains, possibly reflective of a dementia prodrome.

Incidence of postoperative cognitive dysfunction in older women undergoing pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: Postoperative cognitive dysfunction (POCD), a transient impairment of memory, concentration, and information processing, has been reported after 7-26% of non-cardiac surgeries with associated increase in morbidity and death. Our primary aim was to determine the incidence of POCD 2 weeks after prolapse surgery in women ≥ 60 years old. Our secondary aim was to identify risk factors for POCD. METHODS: Prospective cohort study of women ≥ 60 years old scheduled for pelvic organ prolapse surgery. Exclusion criteria included cognitive impairment history, major neurologic disorder, and abnormal cognition screen. A comprehensive neuropsychologic (NP) battery (eight tests), administered 2 weeks pre- and post-surgery, assessed premorbid IQ and domains of attention, memory, and executive function. The primary outcome was defined as decline of ≥ 1 SD on ≥ 2 NP tests or decline of ≥ 2 SD on ≥ 1 test. Raw scores were transformed to Z-scores. RESULTS: NP testing was completed by 72 women, median age 72 (IQR 69-77) years. Procedures included 16 (22.9%) laparoscopic sacrocolpopexies, 23 (32.9%) transvaginal reconstructions, and 29 (41.4%) obliterative surgeries, performed under general (63, 90%), regional (5, 7.1%), or sedation (2, 2.9%) anesthesia with a median hospital stay of 0.6 (IQR 0.6-0.75) days. POCD incidence was 33.3% (n = 24). POCD was associated with greater frailty (p = 0.006) and higher baseline depression (p = 0.05) but not with older age (p = 0.77) or inhalational gas use (p = 1.0). CONCLUSION: In this cohort, one in three women manifested POCD 2 weeks after prolapse surgery. Preoperative counseling should include discussions on POCD given its detrimental impact on postoperative recovery and independence.

A randomized controlled trial of amyloid positron emission tomography results disclosure in mild cognitive impairment.

INTRODUCTION: Recent studies suggest that Alzheimer's disease (AD) biomarker disclosure has no discernable psychological impact on cognitively healthy persons. Far less is known about how such results affect symptomatic individuals and their caregivers. METHODS: Randomized controlled trial of 82 mild cognitive impairment (MCI) patient and caregiver dyads (total n = 164) to determine the effect of receiving amyloid positron emission tomography results on understanding of, and perceived efficacy to cope with, MCI over 52 weeks of follow-up. RESULTS: Gains in the primary outcomes were not consistently observed. Amyloid negative patients reported greater perceived ambiguity regarding MCI at follow-up, while moderate and sustained emotional distress was observed in patients, and to a lesser extent, caregivers, of those who were amyloid positive. There was no corresponding increase in depressive symptoms. DISCUSSION: These findings point to the possibility that both MCI patients and caregivers may need emotional support after the disclosure of amyloid scan results.

Molecular Senescence Is Associated With White Matter Microstructural Damage in Late-Life Depression.

OBJECTIVES: The authors aim to investigate the association between white matter integrity and accelerated brain aging in late-life depression. METHODS: The authors measured senescence-associated secretory phenotype (SASP) index proteins, cognitive performance, and MRI diffusion tensor imaging (DTI) measures of fractional anisotropy and mean diffusivity-based indices of white matter microstructure measures in 56 older adults with remitted late-life depression. RESULTS: Higher SASP index was significantly correlated with older age (r = 0.42, p = 0.001) and worse executive function performance (r = -0.27, p = 0.04). After controlling for the effect of age, overall cognitive performance, and white matter hyperintensities, the association between SASP and left and right cingulate bundle mean diffusivity remained statistically significant. CONCLUSIONS: Our data suggest that, in the context of late-life depression, SASP proteins are associated with microstructural abnormalities in white matter tracts in brain and worse executive function performance.

Exercise for Depression: A Feasibility Trial Exploring Neural Mechanisms.

OBJECTIVE: The aim of this study was to test the feasibility of an exercise augmentation to pharmacotherapy in depressed younger and older adults while exploring neural mechanisms. METHODS: A randomized, double-blind, controlled clinical trial was conducted in 15 inactive younger (20-39 years) and older (60-79 years) adults meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a major depressive episode (https://clinicaltrials.gov/ct2/show/NCT02407704). Participants were randomized to receive a 12-week regimen of venlafaxine XR or venlafaxine XR plus supervised exercise. Cardiorespiratory fitness was assessed using a submaximal Vo2 test, and neuroimaging assessments were conducted using a Siemans MAGNETOM 7-Tesla magnetic resonance scanner at the University of Pittsburgh. RESULTS: Attrition was 38% and 14% for the medication and exercise groups, respectively. Attendance was 91% for the exercise intervention. Exploratory analyses revealed an association between improvement in fitness and increased cortical thickness in the anterior cingulate cortex. CONCLUSION: Exercise augmentation to pharmacotherapy is feasible for depressed younger and older adults and may have neural benefits in a core brain region implicated in depression.

Disruption of Neural Homeostasis as a Model of Relapse and Recurrence in Late-Life Depression.

The significant public health burden associated with late-life depression (LLD) is magnified by the high rates of recurrence. In this manuscript, we review what is known about recurrence risk factors, conceptualize recurrence within a model of homeostatic disequilibrium, and discuss the potential significance and challenges of new research into LLD recurrence. The proposed model is anchored in the allostatic load theory of stress. We review the allostatic response characterized by neural changes in network function and connectivity and physiologic changes in the hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system, and circadian rhythm. We discuss the role of neural networks' instability following treatment response as a source of downstream disequilibrium, triggering and/or amplifying abnormal stress response, cognitive dysfunction and behavioral changes, ultimately precipitating a full-blown recurrent episode of depression. We propose strategies to identify and capture early change points that signal recurrence risk through mobile technology to collect ecologically measured symptoms, accompanied by automated algorithms that monitor for state shifts (persistent worsening) and variance shifts (increased variability) relative to a patient's baseline. Identifying such change points in relevant sensor data could potentially provide an automated tool that could alert clinicians to at-risk individuals or relevant symptom changes even in a large practice.