Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.

Fatigue in Ankylosing Spondylitis Is Associated With Psychological Factors and Brain Gray Matter.

Background: Ankylosing spondylitis (AS) is a rheumatic inflammatory disease with unknown etiology, and fatigue is one of the main systemic symptoms of AS. The aim of the current study was to explore the mechanism of AS-associated fatigue (ASF) from multiple aspects, including neuropsychological changes. Method: A total of 120 AS patients and 78 age- and sex-matched healthy individuals were recruited into the study. Fatigue was assessed by the fatigue item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Assessment of Fatigue (MAF) scale. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). The cortical thickness and subcortical gray matter volume were assessed using a Philips Achieva 3.0 T TX MRI scanner. Result: Of the 120 AS patients, 103 (85.8%) reported varying degrees of fatigue. Among these fatigue cases, 33 (32.0%) were in the severe fatigue group (BASDAI-Fatigue ≥ 5), and 70 patients (68.0%) were considered to be in the mild fatigue group (BASDAI-Fatigue > 0 but <5). The BASDAI, ASDAS-CRP, HAD-A, and HAD-D scores of AS patients in the severe fatigue group were all significantly higher than those of patients in the mild fatigue and non-fatigue groups (all, P < 0.05). The structural equation model suggested that AS activity triggered the occurrence of fatigue by inducing psychological change. Finally, head MRI imaging found that the left thalamus volume in AS patients with severe fatigue was significantly larger than that in non-fatigue AS patients and healthy controls (both, P < 0.05). Conclusion: The study revealed neuropsychological factors involved in fatigue in AS.

Predictors of damage accrual in systemic lupus erythematosus: a longitudinal observational study with focus on neuropsychological factors and anti-neuronal antibodies.

OBJECTIVE: Central nervous system disease occurs in over 20% of patients with systemic lupus erythematosus (SLE) resulting in major morbidity and damage. Cognitive dysfunction is common in SLE, but the cause remains uncertain and treatment options are limited. This study explores the influence of clinical, neuropsychological factors and anti-neuronal antibodies on lupus damage accrual. METHOD: A prospective cohort with 99 SLE patients recruited between 2008 and 2013 and followed up in 2016 was established. Baseline evaluations were depression (MINI-Plus), cognitive function evaluating attention, visuospatial memory and executive functions, and anti-neuronal antibodies. Activity index (SLEDAI-2K) and SLICC/ACR Damage Index (SDI) were assessed at baseline and last follow-up. RESULTS: At baseline, median (interquartile range) age was 36.0 years (27.0-45.0), disease duration 3.7 years (0.4-12.4), SLEDAI-2K 6.0 (3.0-12.0), and SDI score 1.0 (0-1.0). Major depression was present in 23%, cognitive deficit in 18%, and received immunomodulators in 36%. Anti-dsDNA/N-methyl-D-aspartate receptor antibodies were present in 19%, anti-ribosomal P in 12%, and anti-neuronal surface P antigen (NSPA) in 5%. After a median follow-up of 55 months (interquartile range 39-78), 11% had damage accrual. In a multivariate analysis, baseline SDI, SLEDAI-2K, and immunomodulators use were associated with final damage, whereas SLEDAI-2K and immunomodulator use were also associated with accrual damage. Models including anti-NSPA showed impact on final and accrual damage. Cognitive deficit, depression, and other autoantibodies were not predictors. CONCLUSIONS: Disease activity and immunomodulator use associate with lupus damage. Of the anti-neuronal antibodies examined, anti-NSPA emerged as a potential poor prognostic factor, probably related to severe SLE onset requiring elevated corticosteroid doses. Key Points • Anti-NSPA may be a worse prognostic factor in SLE. • Other neuropsychological factors do not influence damage.

The characteristics of neuropsychological factors in patients with persistent postural-perceptual dizziness / 中华行为医学与脑科学杂志

Objective To investigate the characteristics of neuropsychological factors in patients with persistent postural-perceptual dizziness(PPPD) and provide the basis for the psychosomatic comprehen-sive treatment. Methods Cartel Personality Test (16PF),Symptom Checklist 90 ( SCL-90),HAMA,HD-MD,SAS and SDS were used to evaluate personality and mental state in patients with PPPD(PPPD group,n=65) and control group(n=63). Dizziness handicap inventory(DHI) was used to evaluate the degree of ver-tigo. The correlation analysis was carried out between the DHI scores and 16-PF,SCL-90 factor scores. Re-sults (1)16PF factor scores:the factor scores of assertiveness(8. 50±1. 84),excitability (6. 59±1. 73), boldness (7. 46±1. 78),sensitivity (7. 25±1. 79),doubtfulness (6. 55±1. 74),fantasy(6. 20±1. 60),anxie-ty(7. 67±1. 61) and tension(6. 81±1. 67) in PPPD group were higher than those in the control group,and the differences were statistically significant ( all P<0. 05). The gregariousness (4. 38± 1. 65), intelligence (4. 51±1. 67),stability (3. 51±1. 75),independence (4. 39±1. 56) and self-discipline (4. 70±1. 82) fac-tor scores in PPPD group were lower than those in the control group,and the differences were statistically sig-nificant (all P<0. 05). ( 2) SCL-90 factor scores:the factor scores of somatization ( 1. 62 ± 0. 40),anxiety (1. 64±0. 56),interpersonal sensitivity ( 1. 79 ± 0. 42),terrifying ( 1. 71 ± 0. 53),total points ( 150. 77 ± 21. 60),total average score (1. 62±0. 51) in PPPD group were higher than those in control group (all P< 0. 05). There were no differences in obsessive-compulsive (1. 50±0. 55),depression (1. 45±0. 44),hostility (1. 69±0. 60),paranoia (1. 76±0. 53),somatization (1. 42±0. 49) and psychotic ( 1. 29±0. 35) between PPPD group and the control group (all P>0. 05). ( 3) The factor scores of HAMA( 9. 08±1. 77) and SAS (37. 88±2. 96)in patients with PPPD were higher than that in the control group,and the differences were statistically significant (all P<0. 05). There was no significant difference in HAMD (6. 19±2. 82) and SDS (36. 36±4. 71) scores between PPPD group and control group (all P>0. 05). (4)The DHI scores were posi-tively correlated with assertiveness,sensitivity,tension and doubtfulness factors of 16PF. The DHI scores were positively correlated with somatization,interpersonal sensitivity,anxiety and terrifying factors of SCL-90. Con-clusion Patients with persistent postural-perceptual dizziness suffer from personality changes,mental disor-ders and anxiety disorder.

The characteristics of neuropsychological factors in patients with persistent postural-perceptual dizziness / 中华行为医学与脑科学杂志

Objective@#To investigate the characteristics of neuropsychological factors in patients with persistent postural-perceptual dizziness(PPPD) and provide the basis for the psychosomatic comprehensive treatment.@*Methods@#Cartel Personality Test (16PF), Symptom Checklist 90 (SCL-90), HAMA, HDMD, SAS and SDS were used to evaluate personality and mental state in patients with PPPD(PPPD group, n=65) and control group(n=63). Dizziness handicap inventory(DHI) was used to evaluate the degree of vertigo.The correlation analysis was carried out between the DHI scores and 16-PF, SCL-90 factor scores.@*Results@#(1)16PF factor scores: the factor scores of assertiveness(8.50±1.84), excitability (6.59±1.73), boldness (7.46±1.78), sensitivity (7.25±1.79), doubtfulness (6.55±1.74), fantasy(6.20±1.60), anxiety(7.67±1.61) and tension(6.81±1.67)in PPPD group were higher than those in the control group, and the differences were statistically significant (all P<0.05). The gregariousness (4.38±1.65), intelligence (4.51±1.67), stability (3.51±1.75), independence (4.39±1.56) and self-discipline (4.70±1.82) factor scores in PPPD group were lower than those in the control group, and the differences were statistically significant (all P<0.05). (2)SCL-90 factor scores: the factor scores of somatization(1.62±0.40), anxiety (1.64±0.56), interpersonal sensitivity (1.79±0.42), terrifying(1.71±0.53), total points(150.77±21.60), total average score (1.62±0.51) in PPPD group were higher than those in control group (all P<0.05). There were no differences in obsessive-compulsive (1.50±0.55), depression (1.45±0.44), hostility (1.69±0.60), paranoia (1.76±0.53), somatization (1.42±0.49) and psychotic (1.29±0.35) between PPPD group and the control group (all P>0.05). (3)The factor scores of HAMA(9.08±1.77) and SAS(37.88±2.96)in patients with PPPD were higher than that in the control group, and the differences were statistically significant (all P<0.05). There was no significant difference in HAMD (6.19±2.82) and SDS (36.36±4.71) scores between PPPD group and control group (all P>0.05). (4)The DHI scores were positively correlated with assertiveness, sensitivity, tension and doubtfulness factors of 16PF.The DHI scores were positively correlated with somatization, interpersonal sensitivity, anxiety and terrifying factors of SCL-90.@*Conclusion@#Patients with persistent postural-perceptual dizziness suffer from personality changes, mental disorders and anxiety disorder.

Neuropsychological Risk Factors to Consider When Assessing for Sexually Abusive Youth.

Present literature exploring neuropsychological characteristics of sexually abusive youth is lacking, especially with regard to females and youth with low intellectual functioning. Moreover, although areas of neuropsychological functioning have been researched in this population, findings are vastly inconsistent and contradictory. Such gaps in the literature create obvious barriers in the ability to adequately assess risk, particularly pertaining to neuropsychological factors that could inform effective treatment, case management, and supervision options. The purpose of this article is to explore neuropsychological and cognitive deficits that may manifest in youth who have and who have not experienced instances of abuse, for those who have and who have not been convicted of a sex offense, and to provide information for treatment providers, case managers, and supervisors regarding when to consider referring for additional testing.

Neuropsychological mechanisms of falls in older adults.

Falls, a common cause of injury among older adults, have become increasingly prevalent. As the world's population ages, the increase in-and the prevalence of-falls among older people makes this a serious and compelling societal and healthcare issue. Physical weakness is a critical predictor in falling. While considerable research has examined this relationship, comprehensive reviews of neuropsychological predictors of falls have been lacking. In this paper, we examine and discuss current studies of the neuropsychological predictors of falls in older adults, as related to sporting and non-sporting contexts. By integrating the existing evidence, we propose that brain aging is an important precursor of the increased risk of falls in older adults. Brain aging disrupts the neural integrity of motor outputs and reduces neuropsychological abilities. Older adults may shift from unconscious movement control to more conscious or attentive motor control. Increased understanding of the causes of falls will afford opportunities to reduce their incidence, reduce consequent injuries, improve overall well-being and quality of life, and possibly to prolong life.

Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

OBJECTIVE: To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). METHODS: From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. RESULTS: Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p <0.0001), and higher/worse affective factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). CONCLUSION: These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI.

Comparison of brain structural variables, neuropsychological factors, and treatment outcome in early-onset versus late-onset late-life depression.

OBJECTIVE: To compare differences in gray matter volumes, white matter and subcortical gray matter hyperintensities, neuropsychological factors, and treatment outcome between early- and late-onset late-life depressed (LLD) subjects. METHODS: We conducted a prospective, nonrandomized, controlled trial at the outpatient clinics at Washington University and Duke University on 126 subjects, aged 60 years or older, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, scored 20 or more on the Montgomery-Asberg Depression Rating Scale (MADRS), and received neuropsychological testing and magnetic resonance imaging. Subjects were excluded for cognitive impairment or severe medical disorders. After 12 weeks of sertraline treatment, subjects' MADRS scores over time and neuropsychological factors were studied. RESULTS: Left anterior cingulate thickness was significantly smaller in the late-onset depressed group than in the early-onset LLD subjects. The late-onset group also had more hyperintensities than the early-onset LLD subjects. No differences were found in neuropsychological factor scores or treatment outcome between early-onset and late-onset LLD subjects. CONCLUSION: Age at onset of depressive symptoms in LLD subjects are associated with differences in cortical thickness and white matter and subcortical gray matter hyperintensities, but age at onset did not affect neuropsychological factors or treatment outcome.