Summary Background Alcoholism exacts a toll on brain white matter microstructure, which has the potential of repair with sobriety. Diffusion tensor imaging (DTI) enables in vivo quantification of tissue constituents and localization of tracts potentially affected in alcoholism and its recovery. Extended longitudinal study of alcoholism's trajectory of effect on selective fiber bundles with sustained sobriety or decline with relapse, heretofore, has not been conducted. Methods Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcoholics and 56 controls examined 2-5 times over 1-8 year intervals. Regions showing group differences were identified with a white matter atlas. For macrostructural comparison, corpus callosum and centrum semiovale volumes were measured on MRI. Findings TBSS identified a large cluster (threshold p<.001), where controls showed significant fractional anisotropy (FA) decline with aging and alcoholics had significantly lower FA than controls regardless of age. Over the examination interval, 27 alcoholics abstained, 10 relapsed into light drinking, and 10 relapsed into heavy drinking (>5kg/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcoholic group; however, the abstainers’ slopes paralleled those of controls, whereas the heavy-drinking relapsers’ slopes showed accelerated aging. Callosal genu and body microstructure but not macrostructure exhibited untoward alcoholism effects. Affected projection and association tracts had an anterior and superior distribution. Interpretation Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcoholics maintaining sobriety over extended periods showed improvement in brain fiber tract integrity reflective of fiber reorganization and myelin restoration, indicative of a neural mechanism explaining recovery.

Advances in treatment have transformed HIV infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 MRIs and a battery of neuropsychological tests collected two or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; CSF-filled spaces showed increase in volume for both groups. Although HIV infected individuals were in good general health, and free of clinically-detectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacological treatment and control of further infection, has the potential of abating decline in associated, higher-order functions, notably, explicit memory, executive functions, self-regulation, and visuospatial abilities.

Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life.

The purpose of this study was to determine whether meeting historical criteria for unsuspected Wernicke's encephalopathy (WE), largely under-diagnosed in vivo, explains why some alcoholics have severe neuropsychological deficits, whereas others, with a similar drinking history, exhibit preserved performance. Demographic, clinical, alcohol related, and neuropsychological measures were collected in 56 abstinent alcoholics and 38 non-alcohol-dependent volunteers. Alcoholics were classified using the clinical criteria established by Caine et al (1997) and validated in their neuropathological study of alcoholic cases. Our alcoholics who met a single criterion were considered 'at risk for WE' and those with two or more criteria with 'signs of WE'. Whole blood thiamine was also measured in 22 of the comparison group and 28 alcoholics. Of the alcoholics examined, 27% met no criteria, 57% were at risk for WE, and 16% had signs of WE. Neuropsychological performance of the alcoholic subgroups was graded, with those meeting zero criteria not differing from controls, those meeting one criterion presenting mild-to-moderate deficits on some of the functional domains, and those meeting two or more criteria having the most severe deficits on each of the domains examined. Thiamine levels were selectively related to memory performance in the alcoholics. Preclinical signs of WE can be diagnosed in vivo, enabling the identification of ostensibly 'uncomplicated' alcoholics who are at risk for neuropsychological complications. The graded effects in neuropsychological performance suggest that the presence of signs of WE explains, at least partially, the heterogeneity of alcoholism-related cognitive and motor deficits.

HIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.

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Summary Women with severe premenstrual syndrome report sleep‐related complaints in the late‐luteal phase, but few studies have characterized sleep disturbances prospectively. This study evaluated sleep quality subjectively and objectively using polysomnographic and quantitative electroencephalographic measures in women with severe premenstrual syndrome. Eighteen women with severe premenstrual syndrome (30.5 ± 7.6 years) and 18 women with minimal symptoms (controls, 29.2 ± 7.3 years) had polysomnographic recordings on one night in each of the follicular and late‐luteal phases of the menstrual cycle. Women with premenstrual syndrome reported poorer subjective sleep quality when symptomatic in the late‐luteal phase compared with the follicular phase (P < 0.05). However, there were no corresponding changes in objective sleep quality. Women with premenstrual syndrome had more slow‐wave sleep and slow‐wave activity than controls at both menstrual phases (P < 0.05). They also had higher trait‐anxiety, depression, fatigue and perceived stress levels than controls at both phases (P < 0.05) and mood worsened in the late‐luteal phase. Both groups showed similar menstrual‐phase effects on sleep, with increased spindle frequency activity and shorter rapid eye movement sleep episodes in the late‐luteal phase. In women with premenstrual syndrome, a poorer subjective sleep quality correlated with higher anxiety (r = −0.64, P = 0.005) and more perceived nighttime awakenings (r = −0.50, P = 0.03). Our findings show that women with premenstrual syndrome perceive their sleep quality to be poorer in the absence of polysomnographically defined poor sleep. Anxiety has a strong impact on sleep quality ratings, suggesting that better control of mood symptoms in women with severe premenstrual syndrome may lead to better subjective sleep quality.

We investigated whether changes in memory or static balance in chronic alcoholics, occurring with abstinence or relapse, are associated with changes in lateral and fourth ventricular volume. Alcoholics meeting DSM-IV criteria for Alcohol Dependence (n = 15) and non-alcoholic controls (n = 26) were examined twice at a mean interval of two years with standard Wechsler Abbreviated Scale of Intelligence (WASI), Wechsler Memory Scale-Revised (WMS-R) tests, an ataxia battery, and structural MRI. At study entry, alcoholics had been abstinent on average for over 4 months and achieved lower scores than controls on WASI General IQ Index, WMS-R General Memory Index, and the ataxia battery. The ten alcoholics who maintained sobriety at retest did not differ at study entry in socio-demographic measures, alcohol use, or WASI and WMS-R summary scores from the five relapsers. At follow-up, abstainers improved more than controls on the WMS-R General Memory Index. Ataxia tended to improve in abstainers relative to controls. Associations were observed between memory and lateral ventricular volume change and between ataxia and fourth ventricular volume change in alcoholics but not in the controls. Both memory and ataxia can improve with sustained sobriety, and brain-behavior associations suggest selective brain structural substrates for the changes observed.