Comprehensive neurocognitive assessment in late-onset depression: A hospital-based cross-sectional comparative study

Study of neuropsychological deficits in late onset depression.

Major depression associated with aging in males may improve with anabolic/androgenic steroid therapy. The efficacy and safety of testosterone therapy in the treatment of depression in elderly hypogonadal males is inconclusive. The following study identifies a subgroup of elderly depressed males who may benefit from testosterone therapy. Participants included 16 elderly eugonadal males with major depressive disorder (DSM-IV criteria) and a Hamilton Rating Scale for Depression (HAM-D) score > 18. Following a single-blind 2-week placebo lead-in, patients were randomly assigned to treatment with either a physiologic dose of testosterone cypionate (TC), 100 mg/week, or supraphysiologic dose of 200 mg/week IM for 6 weeks. Psychometric testing was carried out at entry into the study, at the TC injection baseline, and every 2 weeks thereafter. Tests included an objective measurement, the HAM-D, and the Buss-Durkee Hostility Inventory. One patient meeting inclusion criteria responded during the placebo lead-in; thus, 15 patients were randomly assigned to treatment (100 mg/week, N = 8; 200 mg/week, N = 7). There was a 42% decrease in the mean HAM-D scores from 20.1 to 11.9 (p <.0001). However, the majority of the change was due to improvement in the 10 late-onset (< or = 45 years old) depression patients, whose mean HAM-D score decreased from 19.8 to 9.3 (53%), versus the 5 early-onset depression patients, whose mean HAM-D score decreased from 20.8 to 17.0 (18%) (p =.0110). The TC dose did not affect the response. Similar HAM-D decreases of 43% and 41% occurred for the respective 100- and 200-mg/week doses. The HAM-D responder analysis found that none of 5 early-onset patients had HAM-D response, whereas 6 (60%) of 10 late-onset patients responded (p =.025). Similarly, none of the early-onset patients experienced a remission whereas 5 (50%) of the late-onset patients were categorized as remitters (p =.053). Correlations between the peak and mean total testosterone concentrations and HAM-D change scores suggested that only minimal TC doses were required to produce an antidepressant effect. These data suggest that testosterone therapy would best be limited to men with late-onset depression. The findings suggest that short-term therapy with TC is safe. Long-term treatment safety is unknown. Psychiatrists using testosterone therapy should ascertain that patients have been recently valuated for prostate cancer. If testosterone therapy is initiated, serial serum prostate-specific antigen sampling should be used for monitoring patients' prostate status.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

Neurocognitive Impairment and Dementia in Mood Disorders

Early and late onset depression in old age: different aetiologies, same phenomenology

Background: Major Depressive Disorder (MDD) is a leading contributor to global disability, with variations in its clinical presentation based on age of onset. Early-Onset Depression (EOD) is often associated with genetic vulnerability and affective symptoms, whereas Late-Onset Depression (LOD) is commonly linked to neurocognitive decline and somatic complaints. The objective is to compare the socio-demographic profiles, clinical features, adverse life events, and neurocognitive functions of patients with early-onset and late-onset depression using standardized assessments, including the NIMHANS neuropsychological battery. Material and Methods: This cross-sectional observational study included 120 patients diagnosed with MDD (60 EOD and 60 LOD), attending the psychiatric outpatient department at a tertiary care center in South India. Participants were evaluated for clinical and socio-demographic factors, adverse stressors, and depressive severity (HAM-D). Cognitive assessment was conducted using selected domains of the NIMHANS battery. Statistical analysis was performed using SPSS v21, with a significance level set at p &lt; 0.05. Results: The mean age of EOD participants was 31.96 ± 6.12 years and for LOD was 69.18 ± 4.91 years. Family history of mood disorders was significantly more common in EOD (33.3%) than in LOD (16.7%). Financial loss and chronic disease were major stressors in LOD, while job loss was more frequent in EOD. EOD cases showed greater affective symptoms (e.g., guilt, suicidal ideation), whereas LOD patients presented with more somatic complaints and disturbed sleep. Neurocognitive impairments were significantly higher in LOD across domains of attention, verbal memory, and executive function, with notable differences in Digit Span, RAVLT, Stroop, and Trail Making Tests (p &lt; 0.05). Conclusion: EOD and LOD represent clinically distinct subtypes of MDD. While EOD is associated with familial and emotional symptoms, LOD is marked by cognitive impairment and physical comorbidities. These findings underscore the need for age-specific screening and intervention strategies in depression care. Keywords: Depression, Cognitive Function, Early-Onset Depression, Late-Onset Depression, Neurocognition, NIMHANS Battery.

Risk factors associated with cognitions for late-onset depression based on anterior and posterior default mode sub-networks

Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients

Neuropsychological impairment is a key feature of late-life depression, with deficits observed across multiple domains. However, it is unclear whether deficits in multiple domains represent relatively independent processes with specific neural correlates or whether they can be explained by cognitive deficits in executive function or processing speed. We examined group differences across five domains (episodic memory; executive function; language skills; processing speed; visuospatial skills) in a sample of 36 depressed participants and 25 control participants, all aged ≥ 60 years. The influence of executive function and processing speed deficits on other neuropsychological domains was also investigated. Magnetic resonance imaging correlates of executive function, processing speed and episodic memory were explored in the late-life depression group. Relative to controls, the late-life depression group performed significantly worse in the domains of executive function, processing speed, episodic memory and language skills. Impairments in executive function or processing speed were sufficient to explain differences in episodic memory and language skills. Executive function was correlated with anisotropy of the anterior thalamic radiation and uncinate fasciculus; processing speed was correlated with anisotropy of genu of the corpus callosum. Episodic memory was correlated with anisotropy of the anterior thalamic radiation, the genu and body of the corpus callosum and the fornix. Executive function and processing speed appear to represent important cognitive deficits in late-life depression, which contribute to deficits in other domains, and are related to reductions in anisotropy in frontal tracts.

Association study between plasma GDNF and cognitive function in late-onset depression

Treatment response in late-life depression: the absence of a relationship with white matter hyperintensity volume, executive functioning, and processing speed

Processing speed is a foundational cognitive ability strongly associated with executive functions in children. To precisely interpret children's results in measures of executive functions, it is important to identify variation that is due to differences in executive functions versus processing speed. In this study, we examined the dimensionality of executive functions and processing speed in 3–6 years old preschoolers over six months with two time points. Executive functions and processing speed (i.e., choice reaction time) were assessed using computer-based tests.Confirmatory factor analyses showed that executive functions and processing speed were divided into two dimensions (processing speed+inhibition+switching and updating) at both time points. Regarding executive functions, the findings indicate that in preschoolers, inhibition+switching is inseparable, but updating is separable from processing speed. Findings emphasize the need to critically evaluate the underlying characteristics of different executive function tasks to better understand the development of executive function and its associations with other cognitive and academic skills. Educational relevance statementIn this study, we examined dimensionality of executive functions and processing speed in preschoolers. Executive functions have been identified as important predictors for school readiness and later academic performance. To better understand individual differences in executive functions and their associations with other cognitive and academic skills in early childhood, accurate measures of executive functions are needed. However, there has been concern that other cognitive processes involved in performing various EF tasks might mask variation in executive functions proficiency. Processing speed is one potential source of measurement impurity in measures of executive functions. However, the evidence about the dimensionality of executive functions and processing speed among young children is limited. To precisely interpret the children's results in measures of executive functions, it is important to identify variation that is due to differences in executive functions versus processing speed.

Abnormal Stroop-related event related potentials in patients with late onset depression in remission period

Objective To investigate executive function in late-onset depression (LOD), to assess activation characteristics of prefrontal cortex and to examine the relationship between cognitive deficits and activation in the prefrontal regions. Methods Twenty-nine patients with LOD and 30 normal controls were included in this study. The severity of depression was evaluated by the 17-item Hamilton Depression Scale (HAMD17). Hemoglobin concentration changes in bilateral prefrontal areas were measured during verbal fluency test (VFT) using 44-channel near infrared spectroscopy (NIRS). Results (1) In LOD group, the correct scores of VFT were significantly lower than that of the control group(9.6±2.4 vs. 11.3±2.2, t=-2.89, P<0.01). (2) In VFT, the part of right prefrontal, left inferior frontal gyrus regions in LOD patients were significantly lower than controls (t=- 3.54 to-2.02, all P<0.05). (3) The score of VFT was negatively correlated with retardation factor score (r=-0.52, P<0.01). In LOD group, the spearman correlation analysis showed that the part of prefrontal regions in the VFT was correlated with HAMD17 total score (right, CH4: r=- 0.44, P<0.01), retardation factor score (right, CH7: r=- 0.53, P<0.01; CH12: r=- 0.48, P<0.01; CH17: r=-0.40, P<0.05, CH18: r=-0.48, P<0.01; CH22: r=-0.46, P<0.01; left, CH10: r=-0.41, P<0.05; CH11: r=-0.57, P<0.01; CH15: r=-0.45, P<0.05), anxiety/somatization factor score (left,CH11: r=-0.44, P<0.05; CH15: r=- 0.45, P<0.01) and agitata factor score (right, CH11: r=- 0.38, P<0.05; left, CH19: r=- 0.38, P< 0.05). Conclusion LOD patients may have executive dysfunction and prefrontal dysfunction, which be positively related to severity of depressive symptoms. Key words: Depressive disorder; Frontal lobe; Oxyhemoglobins; Spectroscopy, near-Infrared; Verbal fluency test

Background: While cognitive dysfunction in late-onset depression (LOD) is common, the nature and determinants of this impairment are heterogeneous. It has been suggested that neuropsychological decrements in LOD patients might result from a deficit in processing resources. In order to address this issue, we analyzed processing resources in LOD to see if their decrease explains higher-level cognition (episodic memory and naming capacity) deficits. Methods: Measures of processing speed, working memory, inhibition, episodic memory and naming capacity were administered to 14 LOD inpatients and 14 controls. Results: The LOD patients performed significantly worse than the controls in all domains except for inhibition. Hierarchical regression analyses showed that naming capacity impairment was totally mediated by processing speed and working memory, whereas episodic memory dysfunction was only partially mediated by working memory. Conclusion: The reduction in certain processing resources (working memory, processing speed) in late-onset depressed patients appears to mediate impairments in episodic memory and naming capacity. However, episodic memory impairment cannot only be explained by processing resource decrement in LOD patients, suggesting that a primary episodic memory dysfunction is present in this condition.