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.

Improvements in Functional Disability After Psychotherapy for Depression Are Associated With Reduced Suicide Ideation Among Older Adults.

OBJECTIVE: To evaluate the association between changes in functional disability and suicide ideation among older adults following psychotherapy for depression. METHODS: Sixty-five participants (65-91 years old, 72% White, and 66% female) with depression completed 12 sessions of problem solving therapy (PST) and completed measures of disability (WHO Disability Assessment Schedule 2.0) and suicide ideation (Geriatric Suicide Ideation Scale [GSIS]) at baseline and post-treatment. RESULTS: Hierarchical linear regressions found that reductions in functional disability were associated with overall reductions in suicide ideation on the GSIS (F[4,60] = 4.06, p < 0.01), particularly with the Loss of Worth GSIS subscale (F[4,60] = 7.86, p < 0.001, ΔR2 = 0.140). CONCLUSIONS: Results suggest decreased functional disability following depression treatment is associated with decreased suicide ideation, especially thoughts regarding loss of worth. These results highlight the potential for treatments that reduce functional disability (e.g., PST) to reduce risk of suicide among older adults.

Using the 2020 global pandemic as a springboard to highlight the need for amphibian conservation in eastern Asia.

Emerging infectious diseases are on the rise in many different taxa, including, among others, the amphibian batrachochytrids, the snake fungal disease and the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) virus, responsible for Coronavirus disease 2019 (COVID-19) in mammals. Following the onset of the pandemic linked to COVID-19, eastern Asia has shown strong leadership, taking actions to regulate the trade of potential vector species in several regions. These actions were taken in response to an increase in public awareness, and the need for a quick reaction to mitigate against further pandemics. However, trade restrictions rarely affect amphibians, despite the risk of pathogen transmission, directly, or indirectly through habitat destruction and the loss of vector consumption. Thus, species that help alleviate the risk of zoonoses or provide biological control are not protected. Hence, in view of the global amphibian decline and the risk of zoonoses, we support the current wildlife trade regulations and support measures to safeguard wildlife from overexploitation. The current period of regulation overhaul should be used as a springboard for amphibian conservation. To mitigate risks, we suggest the following stipulations specifically for amphibians. I) Restrictions to amphibian farming in eastern Asia, in relation to pathogen transmission and the establishment of invasive species. II) Regulation of the amphibian pet trade, with a focus on potential vector species. III) Expansion of the wildlife trade ban, to limit the wildlife-human-pet interface. The resulting actions will benefit both human and wildlife populations, as they will lead to a decrease in the risk of zoonoses and better protection of the environment. SIGNIFICANCE STATEMENT: There is an increasing number of emerging infectious diseases impacting all species, including amphibians, reptiles and mammals. The latest threat to humans is the virus responsible for COVID-19, and the resulting pandemic. Countries in eastern Asia have taken steps to regulate wildlife trade and prevent further zoonoses thereby decreasing the risk of pathogens arising from wild species. However, as amphibians are generally excluded from regulations we support specific trade restrictions: I) Restrictions to amphibian farming; II) regulation of the amphibian pet trade; III) expansion of the wildlife trade ban. These restrictions will benefit both human and wildlife populations by decreasing the risks of zoonoses and better protecting the environment.

The relationship of frailty and disability with suicidal ideation in late life depression.

OBJECTIVES: Frailty and disability are commonly found in Late Life Depression (LLD) and have been associated with increased depression severity, health comorbidities and mortality. Additionally, physical frailty has been associated with suicide in later life, independent of presence of a mood disorder. The objective of our study was to assess the associations of physical frailty and functional disability with suicidal ideation, controlling for depression severity and demographic factors, in an older depressed sample. METHODS: This study used data from community-dwelling older adults with major depression. Eligible participants were ≥ 65 years old, completed measures of depression symptom severity (Hamilton Depression Rating Scale-24 item; HDRS-24), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and physical frailty/functional capacity measures. RESULTS: Participants were 88 older adults with a mean age of 71.5 (SD = 6.0) and 66% of the sample was female. Poorer performance on frailty measures of gait speed (B = .239, p = .003) and muscle weakness (B = -.218, p = .01) were significantly associated with higher levels of suicidal ideation, independent of depression severity and demographic factors. Functional disability was also significantly related to suicide ideation, specifically impairment in financial capacity (B = -.290, p = .008), social interaction (B = .408, p < .001), and communication skills (B = .373, p = .001). CONCLUSION: Our findings show that, in LLD, frailty and functional disability are significantly associated with higher levels of suicide ideation, independent of depression symptom severity.

Somatic and anxiety symptoms of depression are associated with disability in late life depression.

Objectives: To assess the relationships of somatic and anxiety symptoms of depression with functional disability in a sample of older adults with late life depression.Method: Data were analyzed from 78 older adults aged 65-88 with current major depression. Somatic and anxiety symptoms from the 24-item Hamilton Depression Rating Scale (HDRS) were summed to create variables measuring severity of these symptoms. Other symptoms of depression were also assessed using the remaining items of the HDRS. Current physical health burden was assessed using the Functional Comorbidity Index (FCI). Disability was measured with the Late Life Function and Disability Instrument (LLFDI) total limitation score. A linear regression analysis was performed to assess the association of somatic and anxiety symptoms with disability independent of other factors.Results: The model accounted for 26.6% of variance in disability, (F(6,51) = 3.1, p = .01). Somatic (B = -1.9, p = .004) and anxiety (B = -3.7, p = .04) symptoms of depression were significantly associated with disability. Other depressive symptoms and physical illness burden were not associated with disability.Discussion: In older adults with major depression, somatic and anxiety symptoms of depression are associated with disability. Identification and treatment to remission of these symptoms may improve functional outcomes among older depressed adults.

Depression Severity, but Not Cognitive Impairment or Frailty, is Associated with Disability in Late-Life Depression.

OBJECTIVES: Assess the relationship of cognitive impairment to disability, accounting for depression severity and frailty, among older adults with late-life depression (LLD). METHODS: Data were analyzed from 78 community-dwelling older adults with LLD and without dementia (age M = 71.9; SD = 6.1). Cognitive functioning was assessed using a comprehensive neuropsychological battery. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HDRS; cutoff ≥15). Frailty was assessed using several motor tests. The World Health Organization Disability Assessment Schedule (WHO-DAS) measured disability status. A linear regression analysis was performed to identify relationships of cognition, frailty and depression severity with disability. RESULTS: The average number of impaired cognitive tests was 2.0 (SD = 1.9), with 28.2% of participants showing no impaired scores. On average participants reported depression severity of 17.3 (SD = 3.6), and disability total score of 15.1 (SD = 6.9). The regression model accounted for 25.1% of the variance in disability, with only depression severity significantly predicting disability status. Burden of cognitive impairment and frailty were not predictive of disability in this sample. CONCLUSIONS: In this sample, only depression severity was associated with increased disability. CLINICAL IMPLICATIONS: These findings have implications for intervention in LLD, as depression severity may represent a more modifiable risk factor for disability.

Determinants of Suicide-related Ideation in Late Life Depression: Associations with Perceived Stress.

Objectives: Perceived stress is emerging as a potential contributing factor in suicide-related ideation in older adults. We hypothesized higher levels of perceived stress would be associated with increased self-reported suicidal ideation independent of depressive symptom severity.Methods: This study used data from community-dwelling older adults aged ≥65 with a current diagnosis of major depression. Eligible participants completed measures of depression symptom severity (Hamilton Depression Rating Scale-17 item), current suicidal ideation (Geriatric Suicide Ideation Scale), and perceived stress (Perceived Stress Scale).Results: Participants were 225 older adults with a mean age of 71.4 (SD = 5.6). Sixty-five percent of the sample was female. Fifteen percent of the variance in suicidal ideation was accounted for by lower education (p = .03), male sex (p = .03) and higher current perceived stress (p < .001). Specifically, stress accounted for 12% of the variance.Conclusions: Perceived stress is an important avenue to increase identification of individuals with a higher risk of suicide-related ideation among older adults with a current diagnosis of major depression.Clinical Implications: Screening for perceived stress may allow for improved screening and prevention of suicidal activity in depressed older adults.

Impaired Financial Capacity in Late-Life Depression: Revisiting Associations with Cognitive Functioning.

OBJECTIVES: Impairment in financial capacity is an early sign of cognitive decline and functional impairment in late life. Cognitive impairments such as executive dysfunction are well documented in late-life major depression; however, little progress has been made in assessing associations of these impairments with financial incapacity. METHODS: Participants included 95 clinically depressed and 41 nondepressed older adults without dementia. Financial capacity (assessed with the Managing Money scale of the Independent Living Scale), cognitive functioning (comprehensive neuropsychological evaluation), and depression severity (Hamilton Depression Rating Scale - 24) were assessed. T tests were used to assess group differences. Linear regression was used to analyze data. RESULTS: Depressed participants performed significantly lower on financial capacity (t = 2.98, p < .01). Among depressed participants, executive functioning (B = .24, p < .05) was associated with reduced financial capacity, controlling for age, gender, education, depression severity, and other cognitive domains. CONCLUSIONS: Our results underscore the importance of assessing financial capacity in older depressed adults as they are likely vulnerable to financial abuse even in the absence of dementia. It will be valuable to assess whether treatment for depression is an effective intervention to improve outcomes.

Latent Classes of Cognitive Functioning Among Depressed Older Adults Without Dementia.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Screening for Executive Dysfunction in Late-Life Depression: Utility of Trail Making Test and Self-Report Measures.

OBJECTIVE: Prior work suggests executive dysfunction (ED) on the Stroop Color and Word Test (SCWT) and the Mattis Dementia Rating Scale-2 Initiation/Perseveration subscale (DRS IP) predicts poor antidepressant response in late-life depression. This study examined if either patient perception of ED or the Trail Making Test Part B (TMT-B) could identify patients with impairment on the SCWT or DRS IP. METHODS: Patients were 65 or older and had a diagnosis of major depression without dementia. Cognition was assessed with the TMT-B, the SCWT, and the DRS IP. A self-reported Perceived Deficits Questionnaire (PDQ) subscale assessed patients' perceptions of ED. RESULTS: In 247 participants (mean age 71.3 years), the PDQ subscale was not associated with test performance. The sensitivity of the TMT-B in identifying impairment on the SCWT or DRS IP was low (35% and 23%, respectively). CONCLUSION: Neither the TMT-B nor self-reports are useful screening tools for ED on the SCWT or DRS IP.

Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment.

OBJECTIVES: To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI). METHODS: Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aß1-42 ), total tau (t-tau), and phosphorylated tau (p-tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group. RESULTS: As compared to the non-SSD group, the SSD group displayed lower CSF Aß1-42 levels (ß = -24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497) or p-tau levels (P = 0.392). Lower CSF Aß1-42 levels were associated with poorer performance on learning (ß = 0.041, S.E. = 0.018, P = 0.021) and memory (ß = -0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau levels were associated with poorer performance on measures of global cognition (ß = 0.022, S.E = 0.008, P = 0.007) and language (ß = -0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05). CONCLUSIONS: MCI participants with SSD displayed diminished CSF Aß1-42 levels but did not differ from non-SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.

Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression.

OBJECTIVES: To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. DESIGN: Prospective cohort study. SETTING: Multicenter, clinic-based. PARTICIPANTS: Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points. MEASUREMENTS: Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype. RESULTS: The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = -2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = -2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = -2.648, p = 0.008) and anterior cingulate (df = 341, t = -3.786, p < 0.001) atrophy. No group differences were observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory. CONCLUSIONS: Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy.

Conservation genomics of the endangered Burmese roofed turtle.

The Burmese roofed turtle (Batagur trivittata) is one of the world's most endangered turtles. Only one wild population remains in Myanmar. There are thought to be 12 breeding turtles in the wild. Conservation efforts for the species have raised >700 captive turtles since 2002, predominantly from eggs collected in the wild. We collected tissue samples from 445 individuals (approximately 40% of the turtles' remaining global population), applied double-digest restriction-site associated DNA sequencing (ddRAD-Seq), and obtained approximately 1500 unlinked genome-wide single nucleotide polymorphisms. Individuals fell into 5 distinct genetic clusters, 4 of which represented full-sib families. We inferred a low effective population size (≤10 individuals) but did not detect signs of severe inbreeding, possibly because the population bottleneck occurred recently. Two groups of 30 individuals from the captive pool that were the most genetically diverse were reintroduced to the wild, leading to an increase in the number of fertile eggs (n = 27) in the wild. Another 25 individuals, selected based on the same criteria, were transferred to the Singapore Zoo as an assurance colony. Our study demonstrates that the research-to-application gap in conservation can be bridged through application of cutting-edge genomic methods.

PATTERNS OF CLINICALLY SIGNIFICANT COGNITIVE IMPAIRMENT IN HOARDING DISORDER.

OBJECTIVES: The cognitive characteristics of individuals with hoarding disorder (HD) are not well understood. Existing studies are relatively few and somewhat inconsistent but suggest that individuals with HD may have specific dysfunction in the cognitive domains of categorization, speed of information processing, and decision making. However, there have been no studies evaluating the degree to which cognitive dysfunction in these domains reflects clinically significant cognitive impairment (CI). METHODS: Participants included 78 individuals who met DSM-V criteria for HD and 70 age- and education-matched controls. Cognitive performance on measures of memory, attention, information processing speed, abstract reasoning, visuospatial processing, decision making, and categorization ability was evaluated for each participant. Rates of clinical impairment for each measure were compared, as were age- and education-corrected raw scores for each cognitive test. RESULTS: HD participants showed greater incidence of CI on measures of visual memory, visual detection, and visual categorization relative to controls. Raw-score comparisons between groups showed similar results with HD participants showing lower raw-score performance on each of these measures. In addition, in raw-score comparisons HD participants also demonstrated relative strengths compared to control participants on measures of verbal and visual abstract reasoning. CONCLUSIONS: These results suggest that HD is associated with a pattern of clinically significant CI in some visually mediated neurocognitive processes including visual memory, visual detection, and visual categorization. Additionally, these results suggest HD individuals may also exhibit relative strengths, perhaps compensatory, in abstract reasoning in both verbal and visual domains.

Introducing One Health to the Ethical Debate About Zoonotic Diseases in Southeast Asia.

Pandemic plans recommend phases of response to an emergent infectious disease (EID) outbreak, and are primarily aimed at preventing and mitigating human-to-human transmission. These plans carry presumptive weight and are increasingly being operationalized at the national, regional and international level with the support of the World Health Organization (WHO). The conventional focus of pandemic preparedness for EIDs of zoonotic origin has been on public health and human welfare. However, this focus on human populations has resulted in strategically important disciplinary silos. As the risks of zoonotic diseases have implications that reach across many domains outside traditional public health, including anthropological, environmental, and veterinary fora, a more inclusive ecological perspective is paramount for an effective response to future outbreaks.

Cervical Syphilitic Lymphadenitis in a 29-Year-Old Female: A Case Report.

Cervical lymphadenopathy is a common condition characterized by the enlargement of lymph nodes. It can have various causes, including infections, inflammatory conditions, and neoplastic processes. Syphilis, a sexually transmitted disease that progresses through multiple stages, can also be a rare cause of cervical lymphadenopathy, particularly in HIV-positive individuals. In this case report, we describe a patient presenting with throat pain, systemic symptoms, and cervical lymphadenopathy, initially clinically suggestive of lymphoma but ultimately determined to be caused by syphilis of unknown duration. This case highlights the importance of considering syphilis in the differential diagnosis of cervical lymphadenitis, particularly in patients with risk factors, such as intravenous drug use and HIV infection, and the need for a thorough evaluation of the patient's social and medical histories to diagnose and treat the condition accurately.

Relapsing Polychondritis in a Patient With Auricular Chondritis and Inflammatory Bowel Disease: A Case Report With Literature Review.

Relapsing polychondritis (RP) most commonly presents as inflammation and degeneration of cartilaginous tissue in the auricles, nasal septum, and lungs (in severe instances). RP is a rare autoimmune condition associated with other autoimmune diseases in 30% of cases. The prevalence of gastrointestinal involvement with RP is tenuous; however, there is a growing collection of case studies associating auricular chondritis with concomitant inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease. We report the case of a 35-year-old patient presenting with autoimmune pancreatitis, with a past medical history of Crohn's disease, primary sclerosing cholangitis (PSC), and suspected RP. Although RP is rare, the disease's multiple clinical presentations and recurrent episodic nature can cause significant diagnostic delays and are often overlooked by physicians. Thus, low disease prevalence may be due to under-recognition and under-reporting of disease symptoms. As RP is a clinical diagnosis, increased awareness of the disease presentation and clinical characteristics may increase disease recognition and improve treatment outcomes.

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.