Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy.

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV + ) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV- controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P<.05) greater rates of white matter volume loss than HIV- control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites.

BACKGROUND: The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern. METHODS: Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short-echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing. RESULTS: Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non-binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes. CONCLUSIONS: Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.

Perseverations during paired-associate learning in Huntington's disease.

Verbal (word) and nonverbal (design) paired-associate tasks were administered to Huntington's disease (HD) patients and healthy control subjects. An AB-AC paradigm, in which the cue stimuli were paired with different responses on the learning (e.g., BED-REST) and test trials (e.g., BED-SHEET), was used. It was hypothesized that HD patients would continue to respond with AB associations on the AC trials. The results were contrary to expectations: Patients showed impaired learning of both verbal and nonverbal associations but did not display a perseverative response style, even when the associative strength between word pairs was manipulated to elicit perseverations. Patients made more nonperseverative than perseverative errors in all conditions, an error pattern similar to that of control subjects. HD patients did not demonstrate increased susceptibility to proactive interference on these associative learning tasks.

Impaired source memory in Huntington's disease and its relation to basal ganglia atrophy.

Memory for contrived facts and the source of those facts was assessed in a group of early-stage HD patients and an age- and education-equated group of healthy control subjects. Fact recall did not differ significantly between the groups, but erroneous source attributions were more common among the HD patients. Like individuals with frontal lobe damage, HD patients have impaired memory for the source of learned information. Volume of the left caudate nucleus on MRI scans correlated with fact recall and source memory measures. These results suggest that this nucleus, or its neocortical projections, play an important role in the coding of context.

Unimpaired verbal memory and oculomotor control in asymptomatic adults with the genetic marker for Huntington's disease.

OBJECTIVE: To determine whether asymptomatic individuals at very high genetic risk for Huntington's disease (HD) have demonstrable cognitive or oculomotor abnormalities. DESIGN: A case-control study was employed. Presence of the chromosome-4 DNA marker linked to the HD phenotype was the criterion for HD risk. SETTING: The Baltimore Huntington's Disease Project Presymptomatic Testing Program at The Johns Hopkins University School of Medicine, Baltimore, Md. PARTICIPANTS: Seventy-six asymptomatic adults at risk for HD, voluntarily enrolled for genetic testing, and determined by clinical examination to be free of major psychiatric disorder or evidence of HD. Twenty were determined to be at greater than or equal to 95% risk for HD; 56 were at less than or equal to 5% risk [corrected]. MEASURES: The Hopkins Verbal Learning Test was used to assess verbal learning and memory. Oculomotor functioning was assessed using Novel-Stimulus, Mirror-Stimulus, and Predictive-Saccade paradigms. Outcome measures included number of correctly recalled words, recognition accuracy, and response bias, as well as saccade latency and number of errors on the Mirror-Stimulus Test. RESULTS: With one exception, all participants performed within the normal range on the Hopkins Verbal Learning Test. In a blind follow-up examination of the individual who performed aberrantly on the Hopkins Verbal Learning Test, she exhibited neurologic and psychiatric changes sufficient for a clinical diagnosis of HD. There were no group differences on the tests of oculomotor functioning. CONCLUSIONS: Young, asymptomatic adults at very high genetic risk for HD are unimpaired in tests of verbal learning and memory and oculomotor functioning.

Assessment of adaptive functioning in Huntington's disease.

The Huntington's Disease Activities of Daily Living (HD-ADL) scale is a 17-item informant-completed instrument for rating adaptive functioning in Huntington's disease (HD) patients. To assess the reliability and clinical correlates of the HD-ADL, it was administered along with the Mini-Mental State Exam (MMSE) and Quantified Neurological Exam (QNE) to 93 HD patients. The HD-ADL has high internal consistency (coefficient alpha = 0.91). Principal components factor analysis of the HD-ADL revealed four factors (General Functioning, Domestic Activities, Home Upkeep, and Family Relationships) accounting for 72% of the total variance. MMSE score, motor impairment score, and duration of disease were the best predictors of HD-ADL score. Similar results were obtained in an independent replication sample of patients. The HD-ADL scores correlate with Shoulson and Fahn's total functional capacity (TFC) index (r = -0.89). The HD-ADL scale is a reliable and valid instrument for assessing adaptive function in HD patients.

Cognitive and motor correlates of everyday functioning in early Huntington's disease.

The present study documents the prevalence of deficits in the ability to carry out a variety of activities of daily living in early Huntington's disease (HD), along with the associated neuropsychological and motor deficits. Eighty patients with HD were assessed with the Huntington's Disease-Activities of Daily Living Questionnaire (HD-ADL). Sixty-seven patients also completed a comprehensive assessment of cognitive and voluntary motor functioning and chorea. The latter measures were correlated with HD-ADL total score and with most HD-ADL items, but not with those items dealing with marital and family relationship adjustment. Findings suggest that psychomotor speed and the ability to regulate attention may be particularly important determinants of everyday functioning in mild HD. Consistent with previously reported observations, this appears to be true even after accounting for individual differences in the severity of chorea and voluntary motor impairment.

A brief assessment of frontal and subcortical functions in dementia.

A brief assessment of cognitive and motor functions associated with the frontal/subcortical system was evaluated for discriminant validity. Patients with dementia of Huntington's disease and Parkinson's disease performed as well as normal control subjects on the Mini-Mental State Exam (MMSE) but significantly worse on the Frontal/Subcortical Assessment Battery (FSAB). Discriminant function analyses yielded significantly higher rates of accurate classification with FSAB and MMSE combined than with MMSE alone. Patients with Alzheimer's disease scored significantly lower than other groups on both measures. The authors recommend the FSAB as an adjunct to the MMSE for brief assessments of patients with suspected frontal or subcortical pathology.

Lateralized control of eye movements in attention deficit hyperactivity disorder.

How does a complex syndrome that involves abnormalities in impulse control and sustained attention influence simple oculomotor responses to visual stimuli? We found that normal children, like adults, were faster in moving their eyes in directions controlled by the right cerebral hemisphere under conditions where there was no warning of the impending target. ADHD children did not show this asymmetry. We speculate that this result reflects a deficit in the vigilance network that serves to maintain the alert state.

Impact of distressed and aggressive behavior.

Two studies examined the hypothesis that distressed behavior induces negative emotions in others but also prompts solicitousness and deters aggression. In Study 1, 48 marital dyads rated various behaviors in terms of their feelings and reactions toward a spouse engaging in each behavior. Distressed behavior prompted both negative and solicitous emotions, but deterred hostile reactions. Aggressive behavior prompted negative feelings and hostile and argumentative reactions. In Study 2, 41 couples rated videotaped examples of a woman engaging in distressed, aggressive, or neutral behavior, with variations in verbal content and nonverbal affect. Examples of distressed behavior prompted more negative feelings and more solicitous feelings than neutral behavior. Aggressive examples prompted more negative feelings and hostile reactions. The studies indicate the importance of distinguishing between distressed and aggressive behavior.