Methamphetamine users show greater than normal age-related cortical gray matter loss.

BACKGROUND: Methamphetamine (Meth) abuse continues to be a major illicit drug of abuse. Neuroimaging findings suggest that Meth is neurotoxic and may alter various brain structures, but the effect of Meth on the aging brain has not been studied. AIM: The aim was to determine regional volumes of cortical gray matter in the brains of adult Meth users versus healthy control subjects, and their interaction with age and Meth-usage variables. DESIGN: Cross-sectional study SETTING: Magnetic resonance imaging (MRI) Research Center located in a university-affiliated hospital. PARTICIPANTS: Thirty-four Meth-dependent subjects (21 men and 13 women; ages 33.1 ± 8.9 years), diagnosed according to DSM-IV criteria, and 31 healthy non-Meth user comparison subjects (23 men and 8 women ages 35.7 ± 8.4 years). MEASUREMENT: Regional gray matter volumes were segmented automatically in all subjects and evaluated in relation to age, using high-resolution MRIs at 3.0 Tesla. FINDINGS: After adjustment for the effects of cranium size, the Meth users showed enhanced cortical gray matter volume loss with age in the frontal (analysis of covariance interaction P = 0.02), occipital (interaction P = 0.01), temporal (interaction P < 0.001) and the insular lobes (interaction P = 0.01) compared to controls, independently of Meth-usage patterns. Additionally, Meth users showed smaller gray matter volumes than control subjects in several subregions (dorsolateral prefrontal: P = 0.02; orbitofrontal: P = 0.03; prefrontal: P = 0.047; superior temporal: P = 0.04). CONCLUSIONS: Methamphetamine users appear to show increased cortical gray matter loss with age which raises the possibility of accelerated decline in mental functioning.

Age-related gray matter shrinkage in a treatment naïve actively drinking alcohol-dependent sample.

BACKGROUND: We previously demonstrated, in a small sample, steeper age-related gray matter shrinkage in treatment naïve alcohol-dependent (TxN) men compared to nonalcoholic controls, but could not separate out the contributions of age and lifetime duration of alcohol use (which were highly correlated) to this effect. In the current study, we have quadrupled the sample size and expanded it to include both men and women to try to replicate and extend the previous findings and to separate the contributions of age and alcohol use to the phenomenon. METHODS: In the current study, we examine cortical gray matter volumes in 18- to 50-year-old TxN (n = 84) versus age and gender comparable controls (n = 67). We used a new Region of Interest Analysis method which accounts for differences in sulcal and gyral enfolding between individuals (Fein et al., 2009a). RESULTS: We found greater age-related gray matter shrinkage in TxN than in controls. Partial correlation analysis showed that the effect was a function of age and not lifetime alcohol burden. CONCLUSIONS: Implications of the findings are discussed in terms of their contribution toward our knowledge of differences between different subpopulations of alcoholics and in terms of their implications for the morbidity of alcohol dependence in an aging national population.

Parietal gray matter volume loss is related to spatial processing deficits in long-term abstinent alcoholic men.

BACKGROUND: We previously demonstrated relatively intact cognitive function (with the exception of suggestive evidence for persistent deficits in spatial information processing) in middle-aged long-term abstinent alcoholics (LTAA, abstinent for 6 months or more) compared to age and gender comparable nonalcoholic controls (NAC) (Fein et al., 2006). METHODS: In the current study, we examine cortical gray matter volumes in the same samples to determine whether gray matter volumes in LTAA are consistent with the cognitive results--i.e., exhibiting gray matter volumes comparable to NAC in most brain regions, except for possible indications of persistent shrinkage in the parietal lobe subserving spatial information processing. RESULTS: We found gray matter shrinkage in LTAA in the parietal lobe consistent with the spatial processing deficits in this same sample. More compelling, in LTAA, the magnitude of parietal gray matter shrinkage was negatively associated with spatial processing domain performance and positively associated with alcohol dose. Gray matter volume deficits were present in the occipital and other cortical tissue, but poorer visuospatial test performance correlated significantly with smaller volumes in the parietal cortex only. CONCLUSIONS: Taken together, the cognitive and structural imaging data provide compelling evidence that chronic alcohol abuse results in shrinkage of the parietal cortex with associated deficits in spatial information processing.

Increased white matter signal hyperintensities in long-term abstinent alcoholics compared with nonalcoholic controls.

BACKGROUND: The harmful effects of alcohol dependence on brain structure and function have been well documented, with many resolving with sufficient abstinence. White matter signal hyperintensities (WMSH) are thought to most likely be consequences secondary to the vascular (i.e., hypertension and atherosclerosis) effects of AD. We hypothesized that such effects would persist into long-term abstinence, and evaluated them in middle-aged long-term abstinent alcoholics (LTAA) compared with age and gender comparable nonalcoholic controls (NAC). METHODS: Ninety-seven participants (51 LTAA and 46 NAC) underwent cognitive, psychiatric, and structural brain magnetic resonance image evaluations. WMSH were identified and labeled as deep or periventricular by an automated algorithm developed in-house. WMSH volumes were compared between groups, and the associations of WMSH measures with demographic, alcohol use, psychiatric, and cognitive measures were examined within group. RESULTS: Long-term abstinent alcoholics had more WMSH than NAC. There was a significant group by age interaction, with WMSH increasing with age in LTAA, but not in NAC. Within LTAA, WMSH load was independently positively associated with alcohol burden and with age. No associations were evident between WMSH volumes and abstinence duration, family drinking history, years of education, or psychiatric or cognitive variables. CONCLUSION: The magnitude of alcohol abuse was related to increased WMSH volume. The presence of an age effect in the LTAA but not the controls indicates a synergistic effect wherein alcohol advances the onset of aging-related WMSH formation. The increased WMSH load did not appear to have any significant clinical correlates, indicating that the white matter lesions in our sample may not have been severe enough to manifest as cognitive deficits. A limitation of the study is that we did not have data on the presence or severity of lifetime or current indices of vascular risk factors such as hypertension, smoking, or diabetes.