Assessment, prevalence, and correlates of frailty among middle-aged adults with HIV in rural Uganda.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

Adults With Mild-to-Moderate Congenital Heart Disease Demonstrate Measurable Neurocognitive Deficits.

Background Neurocognitive impairment is a common complication of congenital heart disease (CHD) as well as acquired cardiovascular disease. Data are limited on neurocognitive function in adults with CHD (ACHD). Methods and Results A total of 1020 individuals with mild-to-moderate ACHD and 497 987 individuals without ACHD from the volunteer-based UK Biobank study underwent neurocognitive tests for fluid intelligence, reaction time, numeric memory, symbol-digit substitution, and trail making at enrollment and follow-up. Performance scores were compared before and after exclusion of preexisting stroke or coronary artery disease as measures of cerebro- and cardiovascular disease. Individuals with ACHD had significantly poorer performance on alpha-numeric trail making, a measure of visual attention and cognitive flexibility, spending 6.4 seconds longer on alpha-numeric trail making (95% CI, 3.0-9.9 seconds, P=0.002) and 2.5 seconds longer on numeric trail making (95% CI, 0.5-4.6 seconds, P=0.034), a measure of visual attention and processing speed. The ACHD cohort had modestly lower performance on symbol-digit substitution, a measure of processing speed, with 0.9 fewer correct substitutions (95% CI, - 1.5 to - 0.2 substitutions, P=0.021). After excluding preexisting stroke or coronary artery disease, individuals with ACHD continued to show poorer performance in all 6 domains (P=NS). Conclusions Individuals with mild-to-moderate ACHD had poorer neurocognitive performance, most significantly in tests of cognitive flexibility, analogous to deficits in children with CHD. These differences appear to be driven by increased burden of cerebro- and cardiovascular disease among individuals with ACHD.

The sensitivity and specificity of statistical rules for diagnosing delayed neurocognitive recovery with Montreal cognitive assessment in elderly surgical patients: A cohort study.

Delayed neurocognitive recovery (DNR) is common in elderly patients after major noncardiac surgery. This study was designed to investigate the best statistical rule in diagnosing DNR with the Montreal cognitive assessment (MoCA) in elderly surgical patients.This was a cohort study. One hundred seventy-five elderly (60 years or over) patients who were scheduled to undergo major noncardiac surgery were enrolled. A battery of neuropsychological tests and the MoCA were employed to test cognitive function at the day before and on fifth day after surgery. Fifty-three age- and education-matched nonsurgical control subjects completed cognitive assessment with the same instruments at the same time interval. The definition of the international study of postoperative cognitive dysfunction (ISPOCD 1) was adopted as the standard reference for diagnosing DNR. With the MoCA, the following rules were used to diagnose DNR: the cut-off point of ≤26; the 1 standard deviation decline from baseline; the 2 scores decline from baseline; and the Z score of ≥1.96. The sensitivity and specificity as well as the area under receiver operating characteristic curve for the above rules in diagnosis of DNR were calculated.The incidence of DNR was 13.1% (23/175) according to the ISPOCD1 definition. When compared with the standard reference, the 2 scores rule showed the best combination of sensitivity (82.6%, 95% confidence interval [CI] 67.1%-98.1%) and specificity (82.2%, 95% CI 76.2%-88.3%); it also had the largest area under receiver operating characteristic curve (0.824, 95% CI 0.728-0.921, P < .001). The cut-off point rule showed high sensitivity (95.7%) and low specificity (37.5%), whereas the 1 standard deviation and the Z score rules showed low sensitivity (47.8% and 21.7%, respectively) and high specificity (93.4% and 97.3%, respectively).Compared with the ISPOCD1 definition, the 2 scores rule with MoCA had the best combination of sensitivity and specificity to diagnose DNR.

Risk Factors of Caregiver Burden Evolution, for Patients With Subjective Cognitive Decline or Neurocognitive Disorders: A Longitudinal Analysis.

BACKGROUND/OBJECTIVES: The identification of factors used to predict caregiver burden may help preventive care. This study aimed to assess the relationship between evolution of patients with subjective cognitive decline (SCD) or progressive neurocognitive disorder (NCD) and evolution of caregiver burden. DESIGN: Observational, longitudinal study. SETTING: The study was conducted in the Clinical and Research Memory Center of the University Hospital of Lyon (France), between the November 1, 2011 and the June 30, 2014, with a maximum follow-up of 30 months. PARTICIPANTS: The study population included outpatients with SCD or NCD at all stages, and their informal caregiver. MEASUREMENTS: The caregiver burden was assessed during 2 visits of the patients and their caregiver, with the short version of the Zarit Burden Inventory (ZBI). Functional, cognitive performance, and behavioral and psychological symptoms were measured twice, concomitantly with the ZBI, using the Instrumental Activities of Daily Living (IADL) scale, the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory (NPI), respectively. Etiology and stage of the cognitive impairment were collected. RESULTS: The population study included 222 patients (mean age at inclusion: 80 years old, 62.9% females), with an average follow-up 12.6 ± 6 months. Proportion of patients with major NCD at the second visit (62.2%) increased compared with inclusion (50.0%). MMSE and IADL decreased between the 2 visits (P < .001), whereas ZBI increased (mean ZBI: 3.2 ± 2 at baseline, mean ZBI: 3.8 ± 2 at follow-up, P < .001). In unadjusted analyses, ZBI tended to be higher for patients whose MMSE decreased of at least 3 points between the visits. ZBI increased over time when IADL decreased (P value for within-patient effect <.001), while it remained stable when the IADL increased. ZBI increased when NPI increased. After mutual adjustment for change of MMSE, IADL, NPI, and etiologies, increase of ZBI over time remained significant when MMSE decreased at least 3 points between baseline and follow-up, when IADL decreased, and when NPI increased of at least 4 points. CONCLUSIONS: In a study population of patients with SCD or NCD at all stages, concomitant decrease of cognitive performance, increase of functional impairment, and increase neuropsychiatric symptoms over time were independently associated with increased caregiver burden. The identification of risk factors associated with an increased caregiver burden over time may allow a better evaluation of the impact of specific interventions on cognitive, behavioral, and functional dimensions of NCD on caregivers. TRIAL REGISTRATION: ClinicalTrials.govNCT02825732.

Clinical assessment of social cognitive function in neurological disorders.

Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an example disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice.

Withdrawal of penicillamine from zinc sulphate-penicillamine maintenance therapy in Wilson's disease: promising, safe and cheap.

BACKGROUND: Penicillamine, once considered the cornerstone of treatment for Wilson disease (WD), is rather expensive and toxic, and often causes neurological worsening. Zinc sulphate, aiming at the treatment of free-copper toxicosis, has emerged as effective, safe and cheap alternative. AIM: To assess the effect of withdrawal of penicillamine from maintenance treatment with penicillamine and zinc sulphate. PATIENTS AND METHODS: 45 patients of WD (M:F: 28:17; age at diagnosis: 13.5+/-63 years), on both penicillamine (P) and zinc sulphate (Zn), couldn't continue penicillamine due to financial constraints. Their clinical data, disability and impairment scores (Schwab and England (S&E) score, Neurological Symptom Score (NSS), and Chu staging) and follow-up data of patients maintained only on zinc sulphate were recorded. RESULTS: Majority of patients (84.4%) had neuropsychiatric manifestations. The mean duration of treatment with penicillamine (P) and zinc sulphate (P+Zn), before stopping penicillamine, was 107.4+/-67.3 months. 40 patients improved variably, while the rest didn't. They received only zinc sulphate for 27.2+/-8.5 months (range: 12 to 34) and 44 patients (97.7%) remained status quo or improved marginally. Only one patient reported worsening in dysarthria. Their disability and impairment scores during combination (penicillamine and zinc sulphate) and Zn alone were: Chu (1.3+/-0.5 vs. 1.5+/-1.9; p=0.4), NSS (1.8+/-3.1 vs. 1.5+/-2.3; p=0.03) and S&E (96.4+/-5.6 vs. 98.6+/-3.5; p=0.03). There were no adverse effects. CONCLUSIONS: Withdrawal of penicillamine from zinc sulphate/penicillamine maintenance therapy for patients with Wilson's disease was effective, safe and economic, for almost all patients. This retrospective study reiterates that zinc sulphate may be used as a preferred mode of treatment for patients with Wilson's disease.

A taxonomy of neurobehavioral functions applied to neuropsychological assessment after head injury.

Neuropsychological dysfunctions after traumatic brain injury are classified into a taxonomy to plan a comprehensive examination, and organize and report findings for diagnosis and treatment: consciousness, information processing, sensorimotor, neurophysiological, cerebral personality disorders, intelligence, memory, language, stress, psychodynamic, identity and weltanschauung, adaptation, complex adaptive functions, and development of children. Wide-range sampling enhances the detection of acute and late-developing dysfunctions, and diagnosis of complex syndromes. Historical, personality, and injury data are components of the assessment. Issues discussed include underestimation of brain injury, malingering, interaction of symptoms, symptom persistence, and noncerebral lesional contributors to impairment after mild head injury.

Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research.

A large number of investigation techniques are used to establish the relationships between the clinical and biological data which are necessary for physiopathological analysis in the field of developmental disorders. It therefore seemed necessary to develop a quantified grouping system, based on developmental assessments, which could allow closer matching between clinical evaluations and biological numerical data. Two hundred and two subjects presenting developmental disorders (autistic disorder, pervasive developmental disorder not otherwise specified and mental retardation) were examined. For each child, a quantification of autistic behaviour, intellectual impairment, neurological signs and language and communication disorders was performed. A cluster analysis of these quantified data elicited four subgroups according to the scores obtained in these four different areas. We showed the value of this approach by applying it to one of the studies of monoamines routinely examined in childhood autism--dopamine and HVA, its main urinary derivative. Moreover, this method revealed a subgroup within the total population which was independent of nosographic classification and which had a particular clinical and biochemical profile. Other applications could follow, for example in the fields of neurophysiology, cerebral imaging, molecular biology and genetics.

Factors complicating the diagnosis of depression in cerebrovascular disease, Part II--Neurological deficits and various assessment methods.

Neurological deficits associated with cerebrovascular disease such as aphasia, dementia, anosognosia and aprosodia may impair the ability to express or experience depressive symptoms. Identification of depression in the absence of verbal report on subjective mood state is a difficult task. The value of various diagnostic methods including depressive rating scales, standard psychiatric interviews and biological variables in the diagnosis of depression in cerebrovascular disease is considered. This review concludes by focusing on the deficiencies of existing approaches in the diagnostic assessment of depression in patients with severe communication and comprehension deficits and emphasizes the importance of devising a standard diagnostic method with less reliance on verbal responses.

The significance of frontal system disorders for medical practice and health policy.

In major chronic diseases, apathy or impaired executive cognitive function (ECF) can reduce the patient's ability to cope with the disease and its treatment and to maintain personal safety, dignity, and goal-directed activity. Psychometric and imaging studies support a causal role for frontal system dysfunction. The view that frontal system dysfunction mediates or aggravates disability in a wide range of psychiatric and nonpsychiatric disorders 1) motivates further research on how ECF deficits interact with specific physical impairments to produce disability; 2) supports policies that base entitlements to care on ECF impairments; and 3) suggests the need for a vigorous search for drugs that prevent or palliate prefrontal dysfunction, especially the syndromes of apathy and impaired ECF.

Assessment of frontal lobe functions.

The authors describe methods for conducting a thorough assessment of functions subserved by the frontal lobes, employing both bedside and psychometric methods of assessing frontal subsystems. Qualitative or process aspects of frontal behavior observable from formal testing, interview, and social behavior are noted. It is argued that the skilled clinician must be guided by a knowledge of frontal lobe subsystems and their roles in determining specific types of abnormal behavior. The clinician will then be alert to changes in incidental behaviors that indicate frontal impairment, and bedside maneuvers can be designed to discriminate dysfunction. Given the complexity of the behaviors involved and the profound effects of maturation and aging on frontal functions, neuropsychological assessment can provide an invaluable tool for testing these functions.

Neuropsychological assessment in MS: clinical, neurophysiological and neuroradiological relationships.

We assessed cognitive performance and its relationship with clinical and anatomic disease severity in MS with mild to moderate handicap; 34 definite MS and 18 healthy subjects matched for age and education were submitted to a neuropsychological test battery. Both groups were examined for anxiety. MS patients underwent magnetic resonance imaging examination. MS performed worse than controls on all WAIS-P subtests and had learning, short- and long-term verbal memory impairment. Cognitive deficits were not related to abnormal emotional states, but were found to be associated with attentional process and information-processing speed impairment. Cognitive impairment did not correlate with severity of physical disability. The most severe memory deficits were found in patients with extensive periventricular damage.

Alpha reactivity in schizophrenia and in schizophrenic spectrum disorders: demographic, clinical and hemispheric assessment.

Alpha EEG reactivity was assessed in a carefully diagnosed sample of 84 schizophrenic and schizophrenic spectrum disorder patients, both under resting conditions (eyes closed and eyes open) and during two spatial-geometric cognitive tasks. The influence of the subject's demographic (sex and age), clinical (diagnostic subtypes, disease course, CT scan characteristics) and neurophysiological (hemispheric recording and different cognitive tasks) characteristics on alpha peak reactivity was analyzed by means of multivariate analysis of variance. The results indicated a significant effect of type of illness on alpha EEG reactivity, patients with a diagnosis of undifferentiated and disorganized schizophrenia having the lowest alpha reactivity levels. None of the other variables considered had any contributing effect. The results are discussed in terms of orienting responses and hemispheric CNS organization in functional psychoses.