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ObjectivesGeriatric depression is difficult to treat and frequently accompanied by treatment resistance, suicidal ideations and polypharmacy. New adjunctive mind-body treatment strategies can improve clinical outcomes in geriatric depression and reduce risk for side-effects of pharmacological treatments.MethodsWe conducted a 3-month randomized controlled trial to assess the efficacy and tolerability of combining Tai Chi Chih (TCC) or Health Education and Wellness training (HEW) with the stable standard antidepressant treatment on mood and cognitive functioning in depressed older adults (NCT02460666). Primary outcome was change in depression as assessed by the Hamilton Rating Scale for Depression (HAM-D) post-treatment. Remission was defined as HAM-D ≤ 6; naturalistic follow-up continued for 6 months. We also assessed psychological resilience, health-related quality of life and cognition.ResultsOf the 178 randomized participants, 125 completed the 3-month assessment and 117 completed the 6-month assessment. Dropout and tolerability did not differ between groups. Remission rate within TCC was 35.5% and 33.3%, compared to 27.0% and 45.8% in HEW, at 3 and 6 months respectively (χ2(1) = 1.0, p = 0.3; χ2(1) = 1.9, p =0.2). Both groups improved significantly on the HAM-D at 3 and 6 months. TCC demonstrated a greater improvement in general health compared to HEW.ConclusionsBoth TCC and HEW combined with a standard antidepressant treatment improved symptoms of depression in older adults. While TCC was superior to HEW in improving general health, we did not find group differences in improvement in mood and cognition.

ObjectiveGeriatric depression is difficult to treat and frequently accompanied by cognitive complaints that increase risk for dementia. New treatment strategies targeting both depression and cognition are urgently needed.MethodsWe conducted a 6-month double-blind placebo-controlled trial to assess the efficacy and tolerability of escitalopram + memantine (ESC/MEM) compared to escitalopram + placebo (ESC/PBO) for improving mood and cognitive functioning in depressed older adults with subjective memory complaints (NCT01902004). Primary outcome was change in depression as assessed by the HAM-D post-treatment (at 6 months). Remission was defined as HAM-D ≤6; naturalistic follow-up continued until 12 months.ResultsOf the 95 randomized participants, 62 completed the 6-month assessment. Dropout and tolerability did not differ between groups. Mean daily escitalopram dose was 11.1 mg (SD = 3.7; range: 5-20 mg). Mean daily memantine dose was 19.3 mg (SD = 2.6; range 10-20 mg). Remission rate within ESC/MEM was 45.8% and 47.9%, compared to 38.3% and 31.9% in ESC/PBO, at 3 and 6 months, respectively (χ2(1) = 2.0, p = 0.15). Both groups improved significantly on the HAM-D at 3, 6, and 12 months, with no observed between-group differences. ESC/MEM demonstrated greater improvement in delayed recall (F(2,82) = 4.3, p = 0.02) and executive functioning (F(2,82) = 5.1, p = 0.01) at 12 months compared to ESC/PBO.ConclusionsThe combination of memantine with escitalopram was well tolerated and as effective as escitalopram and placebo in improving depression using HAM-D. Combination memantine and escitalopram was significantly more effective than escitalopram and placebo in improving cognitive outcomes at 12 months. Future reports will address the role of biomarkers of aging in treatment response.

Background Anxiety symptoms and disorders are common in older adults and often go undetected. A systematic review was completed to identify tools that can be used to detect anxiety symptoms and disorders in community-dwelling older adults. Methods MEDLINE, Embase and PsycINFO were searched using the search concepts anxiety, older adults and diagnostic accuracy in March 2023. Included articles assessed anxiety in community-dwelling older adults using an index anxiety tool and a gold standard form of anxiety assessment and reported resulting diagnostic accuracy outcomes. Estimates of pooled diagnostic accuracy outcomes were completed. Results Twenty-three anxiety tools were identified from the 32 included articles. Pooled diagnostic accuracy outcomes were estimated for the Geriatric Anxiety Inventory (GAI)-20 [ n  = 3, sensitivity = 0.89, 95% confidence interval (CI) = 0.70–0.97, specificity = 0.80, 95% CI = 0.67–0.89] to detect generalized anxiety disorder (GAD) and for the GAI-20 (n  = 3, cut off ≥ 9, sensitivity = 0.74, 95% CI = 0.62–0.83, specificity = 0.96, 95% CI = 0.74–1.00), Beck Anxiety Inventory (n  = 3, sensitivity = 0.70, 95% CI = 0.58–0.79, specificity = 0.60, 95% CI = 0.51–0.68) and Hospital Anxiety and Depression Scale (HADS-A) (n  = 3, sensitivity = 0.78, 95% CI = 0.60–0.89, specificity = 0.76, 95% CI = 0.60–0.87) to detect anxiety disorders in clinical samples. Conclusion The GAI-20 was the most studied tool and had adequate sensitivity while maintaining acceptable specificity when identifying GAD and anxiety disorders. The GAI-20, GAI-Short Form and HADS-A tools are supported for use in detecting anxiety in community-dwelling older adults. Brief, self-rated and easy-to-use tools may be the best options for anxiety detection in community-dwelling older adults given resource limitations. Clinicians may consider factors including patient comorbidities and anxiety prevalence when selecting a tool and cut off. [ABSTRACT FROM AUTHOR]

BackgroundSeveral modifiable lifestyle factors have been shown to have potential beneficial effects in slowing cognitive decline. Two such factors that may affect cognitive performance and slow the progression of memory loss into dementia in older adults are cognitive training and physical activity. There are currently no effective treatments for dementia; therefore, preventative strategies to delay or prevent the onset of dementia are of critical importance.ObjectiveThe aim of this study was to determine the relative effectiveness of simultaneous performance of memory training and aerobic exercise to a sequential performance intervention on memory functioning in older adults.Methods55 older adults (aged 60- 75) with subjective memory impairments (non-demented and non-MCI) completed the intervention that consisted of 90-minute small group classes held twice weekly. Participants were randomized to either 4-weeks of supervised strategy-based memory training done simultaneously while stationary cycling (SIM) or sequentially after the stationary cycling (SEQ). Standardized neurocognitive measures of memory, executive functioning, speed of processing, attention, and cognitive flexibility were assessed at baseline and post-intervention.ResultsThe SIM group, but not the SEQ group, had a significant improvement on composite memory following the intervention (t(51) = 2.7, p = 0.01, effect size (ES) = 0.42) and transfer to non-trained reasoning abilities (t(51) = 6.0, ES = 0.49) and complex attention (t(51) = 3.1, p = 0.003, ES = 0.70). Conversely, the SEQ group, but not the SIM, showed significant improvement in executive functioning (t(51) = 5.0, p = 0.0001, ES = 0.96).ConclusionThese findings indicate that a 4-week simultaneous memory training and aerobic exercise program is sufficient to improve memory, attention, and reasoning abilities in older adults.

Screening for social determinants of health, including maternal depression, is a recommended pediatric practice. However, the magnitude of association between maternal and child screening tools remains to be determined. The current study evaluated the association between maternal postnatal depressive symptoms and child developmental milestones, as well as moderators of these associations. A comprehensive search strategy was carried out in four databases (MEDLINE, EMBASE, APA PsycINFO, and Cochrane Central Register of Controlled Trials) from database inception to September 2022. Studies that examine postnatal depressive symptoms and associations with infant and early child (<6 years) achievement of developmental milestones were included. Data were extracted by two independent coders and a random‐effects meta‐analysis was used to estimate pooled effect sizes and test for moderators. A total of 38 non‐overlapping studies (95,897 participants), all focused on maternal postnatal depression, met inclusion criteria. The pooled effect size for the association between postnatal depressive symptoms and early achievement of infant and child developmental milestones (N = 38; r = −.12; 95% CI = −.18, −.06) was small in magnitude. Child age at maternal depression measurement was a moderator, whereby effect sizes became greater for older children. Despite small effects, maternal postnatal depressive symptoms should be included in screening during routine well‐child visits to enhance child development outcomes. [ABSTRACT FROM AUTHOR]

Background: Older adults experience symptoms of depression, leading to suffering and increased morbidity and mortality. Although we have effective depression therapies, physical distancing and other public health measures have severely limited access to in-person interventions. Objective: To describe the efficacy of virtual interventions for reducing symptoms of depression in community-dwelling older adults. Design: Systematic review. Setting: We searched MEDLINE, EMBASE, Cochrane Libraries, PsycINFO, and gray literature from inception to July 5, 2021. Participants and interventions: We included randomized trials (RCTs) comparing the efficacy of virtual interventions to any other virtual intervention or usual care in community-dwelling adults ≥60 years old experiencing symptoms of depression or depression as an outcome. Measurements: The primary outcome was change in symptoms of depression measured by any depression scale. Results: We screened 12,290 abstracts and 830 full text papers. We included 15 RCTs (3100 participants). Five RCTs examined persons with depression symptoms at baseline and ten examined depression as an outcome only. Included studies demonstrated feasibility of interventions such as internet or telephone cognitive behavioral therapy with some papers showing statistically significant improvement in depressive symptoms. Conclusions: There is a paucity of studies examining virtual interventions in older adults with depression. Given difficulty in accessing in-person therapies in a pandemic and poor access for people living in rural and remote regions, there is an urgent need to explore efficacy, effectiveness, and implementation of virtual therapies. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with neuronal cell death that is thought to involve aberrant immune responses. Here we investigated the role of innate immunity in a mouse model of ALS. We found that inflammatory monocytes were activated and that their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We also found a decrease in resident microglia in the spinal cord with disease progression. Prior to disease onset, splenic Ly6Chi monocytes expressed a polarized macrophage phenotype (M1 signature), which included increased levels of chemokine receptor CCR2. As disease onset neared, microglia expressed increased CCL2 and other chemotaxis-associated molecules, which led to the recruitment of monocytes to the CNS by spinal cordderived microglia. Treatment with anti-Ly6C mAb modulated the Ly6Chi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss, and extended survival. In humans with ALS, the analogous monocytes (CD14+CD16-) exhibited an ALS-specific microRNA inflammatory signature similar to that observed in the ALS mouse model, linking the animal model and the human disease. Thus, the profile of monocytes in ALS patients may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach., Introduction ALS causes progressive weakness associated with degeneration of motor neurons. Mutations in more than 50 human genes cause diverse types of motor neuron pathology (1). Although ALS is not [...]

Objective To investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS). Methods NanoString microRNA, microglia and immune gene profiles, protein mass spectrometry, and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes, and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice. Results In SOD1 mice, we found loss of the molecular signature that characterizes homeostatic microglia and increased expression of miR-155. There was loss of the microglial molecules P2ry12, Tmem119, Olfml3, transcription factors Egr1, Atf3, Jun, Fos, and Mafb, and the upstream regulators Csf1r, Tgfb1, and Tgfbr1, which are essential for microglial survival. Microglia biological functions were suppressed including phagocytosis. Genetic ablation of miR-155 increased survival in SOD1 mice by 51 days in females and 27 days in males and restored the abnormal microglia and monocyte molecular signatures. Disease severity in SOD1 males was associated with early upregulation of inflammatory genes, including Apoe in microglia. Treatment of adult microglia with apolipoprotein E suppressed the M0-homeostatic unique microglia signature and induced an M1-like phenotype. miR-155 expression was increased in the spinal cord of both familial and sporadic ALS. Dysregulated proteins that we identified in human ALS spinal cord were restored in SOD1G93A/miR-155−/− mice. Intraventricular anti-miR-155 treatment derepressed microglial miR-155 targeted genes, and peripheral anti-miR-155 treatment prolonged survival. Interpretation We found overexpression of miR-155 in the SOD1 mouse and in both sporadic and familial human ALS. Targeting miR-155 in SOD1 mice restores dysfunctional microglia and ameliorates disease. These findings identify miR-155 as a therapeutic target for the treatment of ALS. ANN NEUROL 2015;77:75-99 [ABSTRACT FROM AUTHOR]

A correction to the article "Identification of a unique TGF-beta-dependent molecular and functional signature in microglia," by Oleg Butovsky et al. that was published in a previous issue of the journal is presented.