Effects of HIV and Early Life Stress on Amygdala Morphometry and Neurocognitive Function

Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals. (JINS, 2012, 19, 1-12).     

Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV? and higher in HIV subtype B compared with C. Individuals with HIV (n?=?39) as well as seronegative controls (n?=?22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV? group: current MDD, 15 (38.5 %) vs. 0 (0 %), p?=?0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p?=?0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV? (13 (8–27.5) vs. 2.5 (1–5.5); p?<?0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p?=?0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV?. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.     

Effects of HIV and childhood trauma on brain morphometry and neurocognitive function

A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n?=?32), HIV-positive without ELS (n?=?30), HIV-negative with ELS (n?=?31) and HIV-negative without ELS (n?=?31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.     

White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV?; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV? groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV? group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.     

Quality of Life,Integrative Community Therapy,Family Support,and Satisfaction with Health Services Among Elderly Adults with and without Symptoms of Depression

The aim of this cross-sectional study was to analyse quality of life, socio-demographic characteristics, family support, satisfaction with health services, and effect of integrative community therapy among non-institutionalised elderly adults with and without symptoms of depression in the state of Rio Grande do Norte, Brazil. Data from elderly adults with (n = 59) and without (n = 61) depressive symptoms were compared. The instruments used were the Mini-Mental State Examination, the short version of the Geriatric Depression Scale, a clinical socio-demographic questionnaire, the abbreviated version of the World Health Organisation Quality of Life questionnaire, the Family Assessment Device, and the Patient Satisfaction with Mental Health Services Rating Scale. Elderly adults with depressive symptoms had lower quality of life in the social relations domain than did those without depressive symptoms (p = 0.003). In addition, compared with those without depression, fewer elderly adults with depressive symptoms attended integrative community therapy (p = 0.04); they also reported a low degree of family involvement in problem solving (p = 0.04) and showed apathy regarding their satisfaction with health services (p = 0.007). These results have important implications in the decision-making process with regard to strategies for improving the health status of elderly adults with depressive symptoms.     

Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task

Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 %?±?19 vs. 92 %?±?9, p?=?0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p?<?0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p?<?0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p?<?0.001), with a trend towards precuneus activation (p?=?0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.     

Sleep-Wake Patterns of Adolescents with Borderline Personality Disorder and Bipolar Disorder

Sleep-wake patterns are rarely examined in adolescents with borderline personality disorder (BPD) or bipolar disorder (BD). Within a developmental perspective, this study explores the sleep-wake cycle of adolescents aged 12–17 years with BPD or BD and healthy controls (HC) during periods with and without entrainment by school/work schedules. Eighteen euthymic BPD, six euthymic BD, and 20 HC adolescents wore wrist actigraphy during nine consecutive days to assess sleep-wake patterns. During school/work days, BPD adolescents spent more time awake when they were in bed compared to HC and BD adolescents (p = 0.039). On schedule-free days, BPD and BD youths spent more time in bed compared to HC adolescents (p = 0.015). BPD adolescents woke up over 1 h later compared to HC (p = 0.003). Total sleep time was more variable between nights in BPD adolescents compared to the HC group (p = 0.031). Future research should explore if sleep-wake pattern disruptions are a cause or a consequence of BPD symptomatology in adolescents. Addressing sleep-wake pattern during clinical assessment and treatment of BPD adolescents may potentially reduce their symptoms; this therapeutic effect still needs to be evaluated.     

Anxiety and Depressive Symptoms Among Two Seriously Medically Ill Populations and Their Family Caregivers: A Comparison and Clinical Implications

Background

Anxiety and depression are common among patients with acute illness and their families. In oncology, psychosocial services addressing these symptoms are increasingly part of regular practice. Less is known about psychiatric distress among patients with acute neurological injury (ANI) and their family caregivers. To highlight this inequity in psychosocial intervention across medical services, we compared anxiety and depressive symptomatology shortly following diagnosis among patients facing incurable cancer or ANI and their family caregivers.

Methods

Recruited from the same hospital, participants were patients within 8 weeks of receiving a diagnosis of incurable cancer (N = 350) and their family caregivers (N = 275; total patient/caregiver dyads = 275) and patients hospitalized in the Neuroscience ICU in the past 2 weeks (N = 81) and their family caregivers (N = 95; total dyads = 75). Participants reported anxiety and depressive symptoms using the Hospital Anxiety and Depression Scale. Symptomatology was compared across illnesses using independent samples t-tests and multiple regressions controlling for differences in sample demographics.

Results

Patients with ANI (M = 6.90) reported greater anxiety symptoms than those with cancer (M = 5.31, p < .001), while caregivers for patients with ANI (M = 5.45) reported greater depressive symptoms than caregivers for patients with cancer (M = 3.81, p < .001). Results remained when controlling for demographic differences between samples.

Conclusion

This is the first cross-comparison of psychiatric distress in patients and family caregivers affected by two distinct, life-threatening illnesses early in the illness trajectory. Findings support the priority of addressing psychiatric distress among patients with ANI and their family caregivers, as has been emphasized in the psychosocial oncology field.

     

Non-motor and Extracerebellar Features in Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. Pathological studies have demonstrated not only cerebellar and brainstem atrophy, but substantia nigra, motoneurons, basal ganglia, thalamus, and peripheral nerves involvement. These findings may explain non-motor and extra-cerebellar features in SCA2. We accessed the non-motor symptoms and extra-cerebellar signs in SCA2 patients in order to provide a better understanding on pathophysiological mechanisms and natural history of brain degeneration in the disease. Thirty-three SCA2 patients were evaluated and compared with 26 healthy subjects. We investigated the following variables: sleep disorders, cognitive deficit, olfactory impairment, urinary dysfunction, psychiatric symptoms, cramps, pain, movement disorders, and weight loss. SCA2 had a high frequency of REM sleep behavior disorder (48.48 %, N?=?16) as well as excessive daytime sleepiness (42.42 %, N?=?14). Chorea was present in 15.15 % (N?=?5), dystonia in 27.27 % (N?=?9), and parkinsonism in 27.27 % (N?=?9). Slow saccadic pursuit was present in 87.87 % (N?=?29) and ophtalmoparesis in 78.78 % (N?=?26) of patients. Regarding sleep disorders, 18.18 % (N?=?6) of patients had restless leg syndrome. Dysphagia was present in 39.39 % (N?=?13), weight loss 24.24 % (N?=?8), and urinary dysfunction 27.27 % (N?=?9). Cramps was present in only 6 % of patients (N?=?2). This study highlighted the high frequency of non-motor symptoms and extra-cerebellar signs in SCA2. Our findings demonstrate the widespread of nervous system involvement in SCA2 patients and contribute to better understand the natural history of brain degeneration in this genetic condition.     

Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind,placebo-controlled trial

Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and efficacy of both paroxetine and fluconazole for the treatment of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double-blind, placebo-controlled 2 × 2 factorial design study was used. HIV+ individuals with cognitive impairment were enrolled in the 24-week trial. Participants were randomly assigned to one of four groups: (1) paroxetine 20 mg/day, (2) fluconazole 100 mg every 12 h, (3) paroxetine and fluconazole, or (4) placebo. Safety, tolerability, and efficacy were evaluated. Forty-five HIV+ individuals were enrolled. Medications were well tolerated. Compared to no paroxetine arms, HIV+ individuals receiving paroxetine showed improved NPZ8 summary scores, (mean change = 0.25 vs ??0.19, p = 0.049), CalCAP sequential test reaction time (mean change = 0.34 vs ?0.23, p = 0.014), Trail Making Part B test performance (mean change = 0.49 vs ??0.33, p = 0.041), and FAS verbal fluency (mean change = 0.25 vs 0.02, p = 0.020) but a decline in the Letter number sequencing test (mean change = ??0.40 vs 0.26, p = 0.023). Biomarkers of cellular stress, inflammation, and neuronal damage were not affected by paroxetine. HIV+ individuals receiving fluconazole did not show a benefit in cognition and showed an increase in multiple markers of cellular stress compared to the no fluconazole arms. In conclusion, paroxetine was associated with improvement in a summary neuropsychological test measure and in several neuropsychological tests but worse performance in one neuropsychological test. Further studies of paroxetine for the treatment of HAND and to define its precise neuroprotective properties are warranted.     

Vocal emotion processing deficits in HIV-infected individuals

We aimed to explore the brain imaging correlates of vocal emotion processing in a group of HIV+ individuals and to compare the vocal emotion processing of HIV+ individuals with a group of healthy adults. We conducted multiple linear regressions to determine the cerebral correlates of a newly designed vocal emotion processing test in a sub-group of HIV+ individuals who completed the cerebral magnetic resonance scan (n = 36). Separately, we test whether the association between our test scores and each cerebral measure persisted regardless of the presence of neurocognitive impairment. We also calculated differences in average test scores between the total HIV+ group (n = 100) and a healthy adult group (n = 46). We found a positive association between the test scores and several brain area volumes: right frontal, temporal and parietal lobes, bilateral thalamus, and left hippocampus. We found a negative association between inflammatory markers in frontal white matter and the test scores. After controlling by neurocognitive impairment, several brain area volumes remained positively associated to the prosody test scores. Moreover, the whole HIV+ sample had significantly poorer test scores than healthy adults, but only in the subset of HIV+ individuals with neurocognitive impairment. For the first time, our results suggest that cerebral dysfunctions in particular brain areas involved in the processing of emotional auditory stimuli may occur in HIV+ individuals. These results highlight the need for broad characterization of the neuropsychological consequence of HIV brain damages.     

A meta-analysis of HIV and heart rate variability in the era of antiretroviral therapy

Background

Heart rate variability (HRV) has been used to assess autonomic dysfunction since the beginning of the HIV epidemic. Although autonomic failure was commonly detected in HIV and AIDS patients prior to the advent of antiretroviral therapy (ART), the effect of HIV on HRV in the current era of widespread ART availability is more ambiguous.

Methods

A systematic search and review was conducted on cross-sectional observational and case–control studies published in the era of ART (1996–2015) that compared HRV between HIV + individuals treated with ART and HIV ? controls. Eight out of the 20 studies identified, enrolling a total of 292 HIV + adults (mean age 38.7 years) and 201 HIV seronegative controls (mean age 35.1 years), were included in a meta-analysis based on stringent methodological criteria.

Results

At rest, individuals with HIV showed lower HRV in the time (g) = ?0.72, 95 % CI (?1.03 to ?0.42) and low-frequency (LF) domain (g) = ?0.51, (?0.81 to ?0.21); markers of lower parasympathetic tone in the time (g) = ?0.55, (?0.85 to ?0.25) and high-frequency (HF) domain (g) = ?0.42, (?0.71 to ?0.12); and higher LF:HF ratio (g) = 0.46, (0.12–0.86) in the frequency domain, suggestive of parasympathetic withdrawal.

Conclusion

This meta-analysis confirmed, within a relatively young cohort of HIV + adults on ART, a general reduction in autonomic function with a shift toward sympathetic dominance. This shift may predispose HIV patients to early and elevated risk of arrhythmias, cardiac events, and accelerated HIV disease progression.

     

Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals

Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neurocognitive functioning in the context of long-term suppressive antiretroviral therapy (ART). We quantified the levels of cell-free mtDNA in the CSF from 41 HIV-infected individuals with completely suppressed HIV RNA levels in blood plasma (<50 copies/mL) by droplet digital PCR. We measured soluble CD14, soluble CD163, interferon γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), neopterin, and neurofilament light chain (NFL) by immunoassays in CSF supernatant or blood plasma. Higher levels of mtDNA in CSF were associated with higher levels of MCP-1 (r = 0.56, p < 0.01) in CSF and TNF-α (r = 0.43, p < 0.01) and IL-8 (r = 0.44, p < 0.01) in blood plasma. Subjects with a previous diagnosis of AIDS showed significantly higher levels of mtDNA (p < 0.01) than subjects without AIDS. The associations between mtDNA and MCP-1 in CSF and TNF-α in blood remained significant after adjusting for previous diagnosis of AIDS (p < 0.01). Additionally, higher levels of mtDNA were associated with a lower CD4 nadir (r = ?0.41, p < 0.01) and lower current CD4% (r = ?0.34, p = 0.03). Paradoxically, higher levels of mtDNA in CSF were significantly associated with better neurocognitive performance (r = 0.43, p = 0.02) and with less neuronal damage (i.e. lower NFL). Higher cell-free mtDNA is associated with inflammation during treated HIV infection, but the impact on neurocognitive functioning and neuronal damage remains unclear and may differ in the setting of suppressive ART.     

The complement system,neuronal injury,and cognitive function in horizontally-acquired HIV-infected youth

The complement system (C1q/C3) is a key mediator of synaptic pruning during normal development. HIV inappropriately induces C1q and C3 production in the brain, and reduces neuronal complement inhibition. HIV may thus alter neural connectivity in the developing brain by excessively targeting synapses for elimination. The resultant pattern of neuronal injury may fundamentally alter neurodevelopmental and cognitive processes differentially across ages. This study aimed to (1) measure the association between the cerebrospinal fluid (CSF) complement factors (C1q/C3) and a marker of neuronal injury (NFL) in HIV+ subjects; (2) quantify the differences in CSF C1q/C3 between HIV+ youth and older adults; and (3) define the relationship between CSF C1q/C3 and cognitive impairment in each age group. We performed a retrospective cross-sectional study of 20 HIV+ 18–24-year-old youth and 20 HIV+ 40–46-year-old adults with varying levels of cognitive impairment enrolled in the CNS Antiretroviral Therapy Effects Research study. We quantified C3, C1q, and NFL by ELISA in paired CSF/plasma specimens. We found that CSF C1q correlates with NFL in all subjects not receiving antiretroviral therapy (n = 16, rho = 0.53, p = 0.035) when extreme NFL outliers were eliminated (n = 1). There was no difference in plasma/CSF C1q or C3 between older adults and youth. In 18–24-year-old youth, a nearly significant (p = 0.052) elevation of CSF C1q expression was observed in cognitively impaired subjects compared to cognitively normal subjects. Further investigation into the role of the CNS complement system in the neuropathogenesis of HIV is warranted and should be considered in a developmentally specific context.     

Facebook for Supporting a Lifestyle Intervention for People with Major Depressive Disorder,Bipolar Disorder,and Schizophrenia: an Exploratory Study

To examine whether Facebook could support a community-based group lifestyle intervention for adults with serious mental illness. Participants with serious mental illness and obesity enrolled in a 6-month group lifestyle program were invited to join a secret Facebook group to support their weight loss and physical activity goals. Two peer co-facilitators moderated the Facebook group. The proportion of participants who achieved ≥5% weight loss or improved fitness was measured at follow-up. The relationship between this outcome and participants’ interactions in the Facebook group was examined. Interactions were defined as active contributions including posts, comments, or likes. Content of participants’ Facebook posts was also explored. Participants (n = 25) had major depression (44%), bipolar disorder (36%), and schizophrenia (20%). Nineteen (76%) participants joined the Facebook group, and contributed 208 interactions (70 posts; 81 comments; 57 likes). Participants who achieved ≥5% weight loss or improved fitness contributed more interactions in the Facebook group (mean = 19.1; SD = 20.5) compared to participants who did not (mean = 3.9; SD = 6.7), though this relationship approached statistical significance (t = ?2.1; Welch’s df = 13.1; p = 0.06). Participants’ posts containing personal sharing of successes or challenges to adopting healthy behaviors generated more interaction compared to posts containing program reminders (p < 0.01), motivational messages (p < 0.01), and healthy eating content (p < 0.01). Facebook appears promising for supporting health behavior change among people with serious mental illness. These findings can inform social media initiatives to scale up health promotion efforts targeting this at-risk group.     

Depression with Mixed Features in Adolescent Psychiatric Patients

Depression with mixed features is poorly understood, especially in pediatric samples. This study compares symptoms and correlates of depressed adolescent inpatients with mixed features to inpatients with bipolar disorder and major depression. 407 adolescents were administered diagnostic interviews and self-reports, and 262 were categorized as Depression with Mixed Features (MXD; n = 38), Consensus Bipolar (CB; n = 79), or Depression Only (DO; n = 145). Demographic and morbidity information were collected via chart reviews. MXD adolescents evidenced elevated mania-related symptoms compared to DO adolescents. MXD adolescents had elevated Unusually Energetic symptoms and increases for six additional category B mania-related symptoms compared to CB adolescents. MXD adolescents met criteria for more comorbid disorders and reported elevated suicidality, anger, and trauma symptoms compared to CB and DO adolescents. Overall, MXD adolescents evidenced elevated symptomatology compared to other groups, suggesting mixed depression may represent a unique constellation of symptoms meriting further investigation.     

A comparison of the sensitivity,stability, and reliability of three diagnostic schemes for HIV-associated neurocognitive disorders

HIV-associated neurocognitive disorders (HAND) occur in approximately 50% of HIV-infected individuals, yet available diagnostic criteria yield varying prevalence rates. This study examined the frequency, reliability, and sensitivity to everyday functioning problems of three HAND diagnostic criteria (DSM-5, Frascati, Gisslén). Participants included 361 adults with HIV disease and 199 seronegative adults. Neurocognitive status as defined by each of the three diagnostic systems was determined via a comprehensive neuropsychological battery. Everyday functioning was evaluated through self-report and clinician ratings. Results of logistic regressions revealed an association of HIV serostatus with Frascati-defined neurocognitive impairment (p = .027, OR = 1.7[1.1, 2.7]), but not DSM-5 or Gisslén-defined criteria (ps > .05). Frascati and DSM-5 criteria demonstrated agreement on 71% of observations, Frascati and Gisslén showed agreement on 80%, and DSM-5 and Gisslén criteria showed agreement on 46%, though reliability across the three criteria was poor. Only Frascati-defined neurocognitive impairment significantly predicted everyday functioning problems (p = .002, OR = 2.3[1.4, 3.8]). However, when both neurocognitive and complaint criteria were considered, the DSM-5 guidelines demonstrated significant relationships to everyday functioning, serostatus, and also increased reliability overtime compared to neurocognitive criteria alone (all ps < .05). A subset (n = 118) of the HIV+ group was assessed again after 14.0 (2.2) months. DSM-5 criteria evidenced significantly higher rates of incident neurocognitive disorder compared to both Frascati (p = .003) and Gisslén (p = .021) guidelines, while there were fewer remitting neurocognitive disorder diagnoses when Gisslén criteria were applied to the study sample compared to Frascati (p = .04). Future studies should aim to identify gold standard biological markers (e.g., neuropathology) and clinical outcomes associated with specific diagnostic criteria.     

Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age,gender, and the sequence in which drugs were introduced onto the market

The first objective was to determine the long-term retention rate of eight antiepileptic drugs (AEDs) commonly used as adjunctive therapy in adults with focal refractory epilepsy. Second, we assessed the effects of age and gender on retention rates. Third, we examined if the retention rate could be influenced by the sequence in which the AEDs had entered the market. Patients with focal refractory epilepsy treated with any of the eight AEDs in Tampere University Hospital were identified retrospectively (N = 507). Retention rates were evaluated with the Kaplan–Meier method. Follow-up started at the first date of treatment and each individual was followed a maximum of 36 months. We calculated the following 3-year retention rates: lacosamide 77.1% (N = 137), lamotrigine 68.3% (N = 177), levetiracetam 66.7% (N = 319), clobazam 65.6% (N = 130), topiramate 61.6% (N = 178), zonisamide 60.4% (N = 103), pregabalin 54.6% (N = 127), and gabapentin 40.2% (N = 66). Lacosamide, levetiracetam, and clobazam were the most effective AEDs in the elderly. The retention rate for pregabalin was higher in males (65%) than females (51%) whereas females had higher retention rates for both topiramate (72 vs. 58%) and zonisamide (67 vs. 57%). The retention rate was influenced by the sequence in which these AEDs entered the market. We provide important information about practical aspects of these eight AEDs, revealing that there are differences in their effectiveness as adjunctive treatment for focal refractory epilepsy. Most importantly, the retention rate appears to be influenced by the sequence in which these AEDs were introduced onto the market.     

Assessing the Effects of Interpersonal and Intrapersonal Behavior Change Strategies on Physical Activity in Older Adults: a Factorial Experiment

Background

Little is known about which behavior change strategies motivate older adults to increase their physical activity.

Purpose

The purpose of this study was to assess the relative effects of two sets of behavior change strategies to motivate increased physical activity among older adults: interpersonal and intrapersonal.

Methods

Community-dwelling older adults (N = 102, mean age = 79) were randomized in a 2 × 2 factorial experiment to receive interpersonal (e.g., social support, friendly social comparison; no, yes) and /or intrapersonal (e.g., goal setting, barriers management; no, yes) behavior change strategies, combined with an evidence-based, physical activity protocol (Otago exercise program) and a physical activity monitor (Fitbit One?).

Results

Based on monitor data, participants who received interpersonal strategies, compared to those who did not, increased their average minutes of total physical activity (light, moderate, vigorous) per week, immediately (p = .006) and 6 months (p = .048) post-intervention. Similar, increases were observed on measures of functional strength and balance, immediately (p = .012) and 6 months (p = .003) post-intervention. The intrapersonal strategies did not elicit a significant increase in physical activity or functional strength and balance.

Conclusions

Findings suggest a set of interpersonally oriented behavior change strategies combined with an evidence-based physical activity protocol can elicit modest, but statistically and clinically significant, increases in older adults’ physical activity and functional strength and balance.Future research should replicate these findings and investigate the sustained quantity of physical activity elicited by these strategies and their impact on older adults’ quality of life and falls. Trial Registration The ClinicalTrials.gov registration identifier is NCT02433249.