Late-onset epilepsy and 25-year cognitive change: The Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVE: To define the association between late-onset epilepsy (LOE) and 25-year change in cognitive performance. METHODS: The Atherosclerosis Risk in Communities (ARIC) study is a multicenter longitudinal cohort study with participants from four U.S. communities. From linked Medicare claims, we identified cases of LOE, defined as ≥2 seizure-related diagnostic codes starting at age ≥67. The ARIC cohort underwent evaluation with in-person visits at intervals of 3-15 years. Cognition was evaluated 4 times over >25 years (including before the onset of seizures) using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT); a global z-score was also calculated. We compared the longitudinal cognitive changes of participants with and without LOE, adjusting for demographics and LOE risk factors. RESULTS: From 8033 ARIC participants with midlife cognitive testing and Medicare claims data available (4523 [56%] female, 1392 [17%] Black), we identified 585 cases of LOE. The rate of cognitive decline was increased on all measures in the participants who developed LOE compared to those without LOE. On the measure of global cognition, participants with LOE declined by -0.43 z-score points more over 25 years than did participants without epilepsy (95% confidence interval [CI] -0.59 to -0.27). Prior to the onset of seizures, cognitive decline was more rapid on the DWRT, DSST, and global z-scores in those who would later develop LOE than it was in non-LOE participants. Results were similar after excluding data from participants with dementia. SIGNIFICANCE: Global cognition, verbal memory, executive function, and word fluency declined faster over time in persons developing LOE than without LOE. Declines in cognition preceding LOE suggest these are linked; it will be important to investigate causes for midlife cognitive declines associated with LOE.

Late-onset laryngeal paralysis: Owner perception of quality of life and cause of death.

BACKGROUND: Late-onset laryngeal paralysis (LoLP) is an idiopathic disease of older dogs, and is common in the Labrador Retriever. Owner perspective of how LoLP affects their pet's quality of life (QOL), the degree to which LoLP is perceived to be a life-limiting disease, and how a glottic opening procedure affects these perceptions is not known. OBJECTIVES: (a) To determine owner's perception of late-onset laryngeal paralysis (LoLP) with respect to their dog's QOL; (b) To determine whether LoLP is considered by owners to be a life-limiting disease; (c) To evaluate whether a glottic opening procedure altered QOL and perceived cause of death in affected dogs. METHODS: Owners of Labrador Retrievers with LoLP completed a questionnaire. Questions were asked pertaining to a dog's LoLP, including clinical progression and perception of cause of death, and whether a glottic opening procedure was undertaken. Owners also completed a pet-owner administered QOL survey. RESULTS: Seventy-six owners participated. Overall, 94% of owners felt their dog's LoLP affected QOL, and 47% of owners felt LoLP was a large contributing factor in their dog's death. Dogs that underwent a glottic opening procedure were reported to have a better QOL, and the contribution of LoLP towards their death was less than dogs that did not have surgery. CONCLUSION: Owners of Labrador Retrievers with LoLP perceive LoLP to be a life-limiting disease that negatively impacts their dog's QOL. Arytenoid lateralization surgery had a positive impact on QOL in affected dogs.

Are changes in ADHD course reflected in differences in IQ and executive functioning from childhood to young adulthood?

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with poorer cognitive functioning. We used a developmental, genetically-sensitive approach to examine intelligence quotient (IQ) from early childhood to young adulthood among those with different ADHD courses to investigate whether changes in ADHD were reflected in differences in IQ. We also examined executive functioning in childhood and young adulthood among different ADHD courses. METHODS: Study participants were part of the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2232 twins. We assessed ADHD in childhood (ages 5, 7, 10 and 12) and young adulthood (age 18). We examined ADHD course as reflected by remission, persistence and late-onset. IQ was evaluated at ages 5, 12 and 18, and executive functioning at ages 5 and 18. RESULTS: ADHD groups showed deficits in IQ across development compared to controls; those with persistent ADHD showed the greatest deficit, followed by remitted and late-onset. ADHD groups did not differ from controls in developmental trajectory of IQ, suggesting changes in ADHD were not reflected in IQ. All ADHD groups performed more poorly on executive functioning tasks at ages 5 and 18; persisters and remitters differed only on an inhibitory control task at age 18. CONCLUSIONS: Differences in ADHD course - persistence, remission and late-onset - were not directly reflected in changes in IQ. Instead, having ADHD at any point across development was associated with lower average IQ and poorer executive functioning. Our finding that individuals with persistent ADHD have poorer response inhibition than those who remitted requires replication.

Five Personality Traits in Late-onset Depression in Hong Kong.

OBJECTIVE: This study aimed to examine the association between five personality traits and late-onset depression in Hong Kong older people. METHODS: This cross-sectional study included a convenience sample of 40 older people with late-onset depression (LOD) and 54 non-depressed elderly controls. The patients were assessed using the NEO Five Factor Inventory (for personality), the Hamilton Depression Rating Scale (for depression severity), the Mini-Mental State Examination (for cognitive function), the Lawton Instrumental Activities of Daily Living (for functioning), and the Cumulative Illness Rating Scale (for number of physical illnesses). RESULT: The LOD group had a higher Hamilton Depression Rating Scale score (18.9 vs 3.7, p < 0.001), lower Mini Mental State Examination score (24.9 vs 26.4, p = 0.004), and lower Instrumental Activities of Daily Living scale score (21.9 vs 23.7, p = 0.013). On the NEO Five Factor Inventory, the LOD group had a higher neuroticism score (30.7 vs 17.5, p < 0.001) and lower scores on extraversion (19.0 vs 26.4, p < 0.001), openness (18.9 vs 21.5, p = 0.026), and conscientiousness (29.1 vs 33.8, p < 0.001). Neuroticism was the only significant predictor of LOD (odds ratio = 2.325, p = 0.001) and the only significant factor associated with depression severity (ß = 0.581, p = 0.003). CONCLUSIONS: The personality trait of neuroticism is associated with LOD and its severity. Assessment of personality traits should be included in the assessment of people with depression.

Numeracy Skills and Self-Reported Mental Health in People Aging Well.

This study investigated the relationship between numerical accuracy (i.e, number comprehension and mental calculation) and self-reported depression in late adulthood. Whether social context (i.e., marital status) and very early cognitive decline symptoms impacted numerical performance was also examined. Ninety-four community-dwelling elderly participants were recruited in Sardinia, an Italian island characterized by increased longevity. All participants were presented a battery of tests and questionnaires assessing general cognitive efficiency, lifestyle, perceived physical health, numeracy, metacognitive and depressive responses. Number comprehension skills, time spent for gardening, metacognitive performance, and physical health predicted 26% of variance in CES-D index. Furthermore, married participants outperformed single/widowed ones in both number comprehension and mental calculation tasks. The same pattern of results was replicated when cognitively healthy controls were contrasted with participants with some signs of cognitive decline. The assessment of numeracy skills can be very informative in order to promote mental health and life quality in late adult span.

Lasting personality pathology following exposure to severe trauma in adulthood: retrospective cohort study.

BACKGROUND: Early exposure to trauma is a known risk factor for personality disorder (PD), but evidence for late-onset personality pathology following trauma in adults is much less clear. We set out to investigate whether exposure to war trauma can lead to lasting personality pathology in adults and to compare the mental health and social functioning of people with late-onset personality problems with those with PD. METHODS: We recruited patients who scored positively on the International Personality Disorder Examination (IPDE) in southern Croatia 15 years after the Croatian war of independence and used a semi-structured interview to establish when the person's personality-related problems arose. All participants also completed Harvard Trauma Questionnaire, and measures of mental health and social functioning. RESULTS: Among 182 participants with probable personality disorder, 65 (35.7%) reported that these problems started after exposure to war-trauma as adults. The most prevalent personality problems among those with late-onset pathology were borderline, avoidant, schizotypal, schizoid and paranoid. Participants with late-onset personality pathology were more likely to have schizotypal (75.4% vs. 47.3%) and schizoid traits (73.8% vs. 41.1%) compared to those with PD. Participants with late-onset personality pathology were three times more likely to have complex personality pathology across all three DSM-IV clusters compared to those with PD (OR = 2.96, 95% CI 1.54 to 5.67) after adjusted for gender and marital status. The prevalence of depression and social dysfunction were as high among those with late-onset personality pathology as among those with personality disorder. CONCLUSION: Retrospective accounts of people with significant personality pathology indicate that some develop these problems following exposure to severe trauma in adulthood. Personality-related problems which start in adulthood may be as severe as those that have an earlier onset. These findings highlight the long term impact of war trauma on the mental health and have implications for the way that personality pathology is classified and treated.

Value-Based Choice, Contingency Learning, and Suicidal Behavior in Mid- and Late-Life Depression.

BACKGROUND: Suicidal behavior is associated with impaired decision making in contexts of uncertainty. Existing studies, however, do not definitively address whether suidice attempers have 1) impairment in learning from experience or 2) impairment in choice based on comparison of estimated option values. Our reinforcement learning model-based behavioral study tested these hypotheses directly in middle-aged and older suicide attempters representative of those who die by suicide. METHODS: Two samples (sample 1, n = 135; sample 2, n = 125) of suicide attempters with depression (nattempters = 54 and 39, respectively), suicide ideators, nonsuicidal patients with depression, and healthy control participants completed a probabilistic three-choice decision-making task. A second experiment in sample 2 experimentally dissociated long-term learned value from reward magnitude. Analyses combined computational reinforcement learning and mixed-effects models of decision times and choices. RESULTS: With regard to learning, suicide attempters (vs. all comparison groups) were less sensitive to one-back reinforcement, as indicated by a reduced effect on both choices and decision times. Learning deficits scaled with attempt lethality and were partially explained by poor cognitive control. With regard to value-based choice, suicide attempters (vs. all comparison groups) displayed abnormally long decision times when choosing between similarly valued options and were less able to distinguish between the best and second-best options. Group differences in value-based choice were robust to controlling for cognitive performance, comorbidities, impulsivity, psychotropic exposure, and possible brain damage from attempts. CONCLUSIONS: Serious suicidal behavior is associated with impaired reward learning, likely undermining the search for alternative solutions. Attempted suicide is associated with impaired value comparison during the choice process, potentially interfering with the consideration of deterrents and alternatives in a crisis.

Young adult mental health and functional outcomes among individuals with remitted, persistent and late-onset ADHD.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with mental health problems and functional impairment across many domains. However, how the longitudinal course of ADHD affects later functioning remains unclear.AimsWe aimed to disentangle how ADHD developmental patterns are associated with young adult functioning. METHOD: The Environmental Risk (E-Risk) Longitudinal Twin Study is a population-based cohort of 2232 twins born in England and Wales in 1994-1995. We assessed ADHD in childhood at ages 5, 7, 10 and 12 years and in young adulthood at age 18 years. We examined three developmental patterns of ADHD from childhood to young adulthood - remitted, persistent and late-onset ADHD - and compared these groups with one another and with non-ADHD controls on functioning at age 18 years. We additionally tested whether group differences were attributable to childhood IQ, childhood conduct disorder or familial factors shared between twins. RESULTS: Compared with individuals without ADHD, those with remitted ADHD showed poorer physical health and socioeconomic outcomes in young adulthood. Individuals with persistent or late-onset ADHD showed poorer functioning across all domains, including mental health, substance misuse, psychosocial, physical health and socioeconomic outcomes. Overall, these associations were not explained by childhood IQ, childhood conduct disorder or shared familial factors. CONCLUSIONS: Long-term associations of childhood ADHD with adverse physical health and socioeconomic outcomes underscore the need for early intervention. Young adult ADHD showed stronger associations with poorer mental health, substance misuse and psychosocial outcomes, emphasising the importance of identifying and treating adults with ADHD.Declaration of interestNone.

Home-Based Physical Activity Program Improves Depression and Anxiety in Older Adults.

BACKGROUND: Late-life depression and anxiety among older adults is an important public health concern. This study examined the effect of a DVD-delivered exercise intervention on the secondary outcomes of depression and anxiety in older adults and the extent to which physical self-worth mediated the relationship between leisure-time physical activity and depression and anxiety. METHODS: Older adults (N = 307) were randomized to a 6-month flexibility, toning, and balance DVD (FlexToBa™, FTB) or healthy aging DVD control. Self-reported physical activity and questionnaires were administered at baseline and postintervention. Statistical analyses were conducted in the total sample and in a subsample of participants with elevated levels of depression or anxiety. RESULTS: FTB participants with elevated depression and anxiety symptoms at baseline had significantly greater reductions in depression and anxiety (d = 1.66 and 2.90) than the control condition (d = 0.77 and 0.73). The effect of physical activity on depression and anxiety was partially mediated by increases in physical self-worth in the total sample but not in those with elevated depression or anxiety. CONCLUSION: A home-based physical activity intervention may be a viable treatment for reducing depression and anxiety in older adults with elevated baseline scores.

A Machine Learning Approach to Identifying Placebo Responders in Late-Life Depression Trials.

OBJECTIVE: Despite efforts to identify characteristics associated with medication-placebo differences in antidepressant trials, few consistent findings have emerged to guide participant selection in drug development settings and differential therapeutics in clinical practice. Limitations in the methodologies used, particularly searching for a single moderator while treating all other variables as noise, may partially explain the failure to generate consistent results. The present study tested whether interactions between pretreatment patient characteristics, rather than a single-variable solution, may better predict who is most likely to benefit from placebo versus medication. METHODS: Data were analyzed from 174 patients aged 75 years and older with unipolar depression who were randomly assigned to citalopram or placebo. Model-based recursive partitioning analysis was conducted to identify the most robust significant moderators of placebo versus citalopram response. RESULTS: The greatest signal detection between medication and placebo in favor of medication was among patients with fewer years of education (≤12) who suffered from a longer duration of depression since their first episode (>3.47 years) (B = 2.53, t(32) = 3.01, p = 0.004). Compared with medication, placebo had the greatest response for those who were more educated (>12 years), to the point where placebo almost outperformed medication (B = -0.57, t(96) = -1.90, p = 0.06). CONCLUSION: Machine learning approaches capable of evaluating the contributions of multiple predictor variables may be a promising methodology for identifying placebo versus medication responders. Duration of depression and education should be considered in the efforts to modulate placebo magnitude in drug development settings and in clinical practice.

Symptomatic and Functional Recovery From Major Depressive Disorder in the Ibadan Study of Ageing.

OBJECTIVES: Very little is known about the association between symptomatic and functional recovery from late-life major depressive disorder (MDD) in sub-Saharan Africa. We investigated factors associated with sustained symptomatic remission (SR) from MDD and the 5-year trajectory of post-MDD physical functioning. DESIGN: 5-year prospective study with three follow-up waves in 2007, 2008, and 2009. SETTING/PARTICIPANTS: Household multistage probability sample of 2,149 Nigerians who were aged 65 years or older. MEASUREMENTS: Activities of Daily Living (ADL) and MDD were assessed using the Kadz index and Composite International Diagnostic Interview, respectively. We studied those with current MDD (prevalent in 2003-2004 or incident in 2007), and who achieved SR in subsequent waves compared with a chronic/recurrent course (CR). RESULTS: Baseline demographic characteristics, health, and lifestyle factors were not associated with SR in logistic regression analyses. In mixed-effect linear regression models adjusting for age, sex, and socioeconomic status, ADL worsened in SR (ß = 1.0, 95% CI: 0.2, 1.8), but more so in CR (ß = 2.3, 95% CI: 1.6, 3.0). Poorer ADL at follow-up was predicted by age (ß = 2.9, 95% CI: 1.8, 4.0) and economic status (ß = 1.4, 95% CI: 0.3, 2.4). CONCLUSIONS: There was a deteriorating course of disability despite symptomatic recovery from late-life MDD in this sample. This finding has implications for policy and guidelines for the management of late-life depression and disability.

Delirium as presentation of late-onset and relapsing Susac syndrome.

A 67-year-old patient, only known for bilateral presbycusis, presented with subacute onset of delirium. Clinical examination showed multifocal neurological deficits, all together suggesting subcortical frontal dysfunction together with cerebellar and corpus callosum involvement.Cerebral MRI demonstrated supratentorial and infratentorial subcortical and periventricular T2-hyperintense lesions with cerebellar gadolinium enhancement and multiple central lesions of the corpus callosum (snowball lesions). The diagnosis of Susac syndrome was made and the patient treated with intravenous methylprednisolone, followed by a prednisone maintenance dose over 8 weeks. After a clinical improvement, a relapse was noticed during corticosteroid tapering. The patient was again treated with intravenous methylprednisolone followed by a prednisone maintenance therapy with simultaneous introduction of mycophenolate mofetil acid and one cycle of intravenous rituximab. The patient recovered rapidly. At 11-month follow-up, only mild executive dysfunction and persistent right postural tremor was noted, MRI showed partial regression of subcortical and juxtacortical lesions.

Subjects at Risk for Genetic Late-Onset Neurological Diseases: Objective Knowledge.

BACKGROUND/AIMS: This study addresses the objective knowledge about the disease of subjects at risk for 3 genetic late-onset neurological diseases (LOND): familial amyloid polyneuropathy (FAP) TTR V30M, Huntington disease (HD), and Machado-Joseph disease (MJD). METHODS: Subjects at risk for FAP, HD, and MJD submitted to genetic counseling to know their status (carrier or non-carrier) and subjects at risk for hereditary hemochromatosis (HH), the control group, completed a sociodemographic questionnaire and answered the open-ended question: "What do you know about this disease?." RESULTS: From 10 categories of answers, references to the disease, quantitative answers, references to the family, and metaphors stood out. References to the disease, references to the family, and metaphors were mentioned more often by subjects at risk for LOND than by subjects at risk for HH (control group). CONCLUSION: The disease itself and its meaning as well as sick relatives play a key role in the objective knowledge about LOND. Thus, genetic counseling protocols of subjects at risk for LOND should include questions concerning family knowledge and disease experience.

Training social work students to recognize later-life depression: Is standardized patient simulation effective?

Professional social workers are the largest provider of mental health services in the nation, yet they receive little coursework or clinical training in late-life depression unless they are in a gerontology specialization. Simulation training offers academic experiences that evoke conditions of the real world in a practical way. One hundred and four graduate social work students consented and completed the Standardized Patient Simulation course consisting of a human simulator interview, pre- and postdebriefing on late life depression, and self and faculty ratings of outcome measures. Results from pre-post testing of measures and the debriefing evaluation demonstrated that students gained in knowledge and achieved clinical skill competency. Students reported that the patient simulator was convincing, the environment was realistic, and they were satisfied with the training. The educational methodology tests students in challenging situations and offers immediate educational feedback to integrate and improve practice behaviors towards achieving clinical competency.

Childhood Abuse and the Two-Year Course of Late-Life Depression.

OBJECTIVES: Late-life depression often has a chronic course, with debilitating effects on functioning and quality of life; there is still no consensus on important risk factors explaining this chronicity. Cross-sectional studies have shown that childhood abuse is associated with late-life depression, and in longitudinal studies with chronicity of depression in younger adults. We aim to investigate the impact of childhood abuse on the course of late-life depression. DESIGN: Two-year longitudinal cohort study. SETTING: Data were derived from the Netherlands Study of Depression in Older Persons (NESDO). PARTICIPANTS: 282 participants with a depression diagnosis in the previous 6 months (mean age: 70.6 years), of whom 152 (53.9%) experienced childhood abuse. MEASUREMENTS: Presence of childhood abuse (yes/no) and a frequency-based childhood abuse index (CAI) were calculated. Dependent variable was depression diagnosis after 2 years. RESULTS: Multivariable mediation analysis showed an association between childhood abuse and depression diagnosis at follow-up. Depression severity, age at onset, neuroticism, and number of chronic diseases were important mediating variables of this association, which then lost statistical significance. For childhood abuse (yes/no), loneliness was an additional, significant mediator. Depression severity was the main mediating variable, reducing the direct effect by 26.5% to 33.3% depending on the definition of abuse (respectively, 'yes/no" abuse and CAI). CONCLUSIONS: More depressive symptoms at baseline, lower age at depression onset, higher levels of neuroticism and loneliness, and more chronic diseases explain a poor course of depression in older adults who reported childhood abuse. When treating late-life depression it is important to detect childhood abuse and consider these mediating variables.

Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: a meta-analysis of randomized controlled trials.

Although testosterone replacement therapy can restore serum testosterone concentrations to normal level in late-onset hypogonadism patients, whether it can improve patients' quality of life remains uncertain. Therefore, we perform a meta-analysis of randomized controlled trials on this issue. Five randomized controlled trials total 1,212 patients were included. Fixed-effect model was used to calculate the weighted mean difference of score of Aging Males' Symptom rating scale. Our result reveals that testosterone replacement therapy improves patients' health-related quality of life in terms of the decrease in the AMS total score [WMD = -2.96 (-4.21, -1.71), p < .00001] and the psychological [WMD = -0.89 (-1.41, -0.37), p = .0008], somatic [WMD = -0.89 (-1.41, -0.37), p = .0008] and sexual [WMD = -1.29 (-1.75, -0.83), p < .00001] subscale score.

Racial Variation in Depression Risk Factors and Symptom Trajectories among Older Women.

OBJECTIVE: To assess racial variation in depression risk factors and symptom trajectories among older women. METHODS: Using Nurses' Health Study data, participants (29,483 non-Hispanic white and 288 black women) aged 60 years or older, free of depression in 2000, were followed until 2012. Data on race and risk factors, selected a priori, were obtained from biennial questionnaires. Incident depression was defined as depression diagnosis, antidepressant use, or presence of severe depressive symptoms. Group-based trajectories of depressive symptoms were determined using latent variable modeling approaches. RESULTS: Black participants had lower risk (hazard ratio: 0.76; 95% confidence interval: 0.57-0.99) of incident late-life depression compared with whites. Although blacks had higher prevalence than whites of some risk factors at study baseline, distributions of major contributors to late-life depression risk (low exercise, sleep difficulty, physical/functional limitation, pain) were comparable. There was evidence of effect modification by race for relations of region of birth (Southern birthplace), smoking, and medical comorbidity to depression risk; however, wide confidence intervals occurred among blacks because of smaller sample size. Four trajectories were identified: minimal symptoms-stable (58.3%), mild symptoms-worsening (31.4%), subthreshold symptoms-worsening (4.8%), and subthreshold symptoms-improving (5.5%). Probabilities of trajectory types were similar for blacks and whites. CONCLUSION: Although overall trajectories of late-life depressive symptoms were comparable by race, there was racial variation in depression risk estimates associated with less-studied factors, such as U.S. region of birth. Future work may address unmeasured health and resilience determinants that may underlie observed findings and that could inform clinical assessment of late-life depression risk factors.