Alcohol use disorder in elderly suicide attempters: a comparison study.

OBJECTIVES: To compare lifetime prevalence of alcohol use disorder (AUD) in older adults who were hospitalized in connection with a suicide attempt and in a population comparison group, as well as to compare previous suicidal behavior in attempters with and without AUD. DESIGN: Case-comparison. SETTING: Five hospitals in Western Sweden. PARTICIPANTS: Persons 70 years or older, who were treated in a hospital because of a suicide attempt during 2003-2006 were recruited. Of 133 eligible participants, 103 participants were enrolled (47 men, 56 women, mean age 80 years, response rate 77%). Four comparison subjects per case were randomly selected among participants in our late-life population studies. MEASUREMENTS: Lifetime history of AUD in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was discerned on the basis of interview data, case record review, and the hospital discharge register. Depression symptoms were rated using the Montgomery-Åsberg Rating Scale. RESULTS: AUD was observed in 26% of the cases and in 4% of the comparison group (odds ratio [OR]: 10.5; 95% confidence interval [CI]: 4.9-22.5). Associations were noted in men (OR: 9.5; 95% CI: 4.0-22.8) and women (OR: 12.0; 95% CI: 2.4-59.5). More than half of the cases with AUD and a third of those without AUD had made at least one prior suicide attempt. In these, AUD was associated with a longer interval between the first attempt and the index attempt. CONCLUSIONS: A strong association between AUD and hospital-treated suicide attempts was noted in both sexes in this northern European setting. Given the high rates of suicide worldwide in this fast-growing and vulnerable group, comparison studies in other settings are needed.

Midlife psychological distress associated with late-life brain atrophy and white matter lesions: a 32-year population study of women.

OBJECTIVE: Long-standing psychological distress increases the risk of dementia, especially Alzheimer's disease. The present study examines the relationship between midlife psychological distress and late-life brain atrophy and white matter lesions (WMLs), which are common findings on neuroimaging in elderly subjects. METHODS: A population-based sample of 1462 women, aged 38 to 60 years, was examined in 1968, with subsequent examinations in 1974, 1980, 1992, and 2000. Computed tomography (CT) of the brain was done in 379 survivors in 2000, and of those, 344 had responded to a standardized question about psychological distress in 1968, 1974, and 1980. WMLs, cortical atrophy, and central atrophy (ventricular sizes) were measured at CT scans. RESULTS: Compared with women reporting no distress, those reporting frequent or constant distress at one examination or more (in 1968, 1974, and 1980) more often had moderate-to-severe WMLs (multiadjusted odds ratio = 2.39, 95% confidence interval = 1.16-4.92) and moderate-to-severe temporal lobe atrophy (multiadjusted odds ratio = 2.51, 95% confidence interval = 1.04-6.05) on brain CT in 2000. Frequent/constant distress was also associated with central brain atrophy, that is, higher bicaudate ratio, higher cella media ratio, and larger third-ventricle width. CONCLUSIONS: Long-standing psychological distress in midlife increases risks of cerebral atrophy and WMLs on CT in late life. More studies are needed to confirm these findings and to determine potential neurobiological mechanisms of these associations.

Head size may modify the impact of white matter lesions on dementia.

We aimed to examine whether total intracranial volume (TICV), a marker of premorbid brain size, modified the impact of the apolipoprotein E (apoE) e4 phenotype and ischemic white matter lesions (WMLs) on odds for dementia. The study comprised a population-based sample of 104 demented and 135 nondemented 85-year-olds, and included physical and neuropsychiatric examinations, and head computerized tomography (CT). Dementia disorders were defined according to standard criteria. TICV and WMLs were rated on computerized tomography. Using the highest group as reference, the risk for dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was increased in those with the smallest half, tertile, and quartile of TICV. Smaller TICV increased the odds of dementia, Alzheimer's disease, and vascular dementia in participants with WMLs. WMLs were not associated with increased odds of dementia in those with the largest TICV. The interaction term WMLs*TICV was also significant. TICV did not modify the odds of dementia in those with the apolipoprotein e4 phenotype. Our results suggest that the impact of brain pathology on the risk of dementia is modified by premorbid brain size.

Temporal lobe atrophy and white matter lesions are related to major depression over 5 years in the elderly.

The influence of organic brain changes on the development of depression in the elderly is uncertain. Cross-sectional studies, most often from clinical samples, report associations with brain atrophy and cerebrovascular disease, while longitudinal population studies have given mixed results. Our aim was to investigate whether cortical atrophy and white matter lesions (WMLs) on computed tomography (CT) predict occurrence of depression in the elderly. This is a prospective population-based study with 5-year follow-up. The baseline sample included 525 elderly subjects, aged 70-86 years, without dementia or major depression, with a score on the Mini-Mental State Examination above 25, and without dementia at follow-up. Cortical atrophy and WMLs were evaluated at baseline using CT. The main outcome measure was development of major or minor depression at follow-up according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, as evaluated using neuropsychiatric examinations and hospital discharge registers. Logistic regression was used to estimate risk. Over the period of 5 years, 20 individuals developed major and 63 minor depression. Presence of temporal lobe atrophy (odds ratio (OR)=2.81, 95% confidence interval (CI) 1.04-7.62) and moderate-to-severe WMLs (OR=3.21, 95% CI 1.00-10.26) independently predicted major, but not minor, depression after controlling for various confounders. Other brain changes did not predict occurrence of depression. Our findings suggest that temporal lobe atrophy and WMLs represent relatively independent and complementary pathways to major depression in the elderly. This may have implications for prevention, as both neurodegeneration and cerebrovascular disease have been related to preventable factors.

High education may offer protection against tauopathy in patients with mild cognitive impairment.

The concepts of brain and cognitive reserve stem from the observation that premorbid factors (e.g., education) result in variation in the response to brain pathology. Potential early influence of reserve on pathology, as assessed using the cerebrospinal fluid biomarkers total tau (t-tau) and amyloid-beta42, and cognition was explored in mild cognitive impairment (MCI) patients who remained stable over a two-year period. A total of 102 patients with stable MCI grouped on the basis of educational level were compared with regard to biomarker concentrations and cognitive performance. Stable MCI patients with higher education had lower concentrations of t-tau as compared to those with lower education. Also, educational level predicted a significant proportion of the total variance in t-tau concentrations. Our results suggest that higher education may offer protection against tauopathy.

HIV infection affects parietal-dependent spatial cognition: evidence from mental rotation and hierarchical pattern perception.

Human immunodeficiency virus (HIV) in the asymptomatic phase of the infection impairs some aspects of cognition, but little is known about how visuospatial functions are affected. In the present study, performance on tasks of mental rotation and hierarchical pattern perception was investigated in 14 HIV-positive men and 12 age- and education-matched HIV-negative men. Processes related to mental rotation of objects and hands were impaired in HIV-positive participants as compared to the HIV-negative group. The HIV-positive group was also impaired on hierarchical pattern perception of local targets under global biasing conditions. Consistent with these results, the HIV-positive participants showed impaired performance on standard clinical neuropsychological tests of visuospatial function. These findings indicate that the detrimental effects of HIV on cognition appear even in asymptomatic individuals and affect diverse visuospatial functions that depend upon the integrity of parietal brain regions.

Brain activity related to working memory and distraction in children and adults.

In order to retain information in working memory (WM) during a delay, distracting stimuli must be ignored. This important ability improves during childhood, but the neural basis for this development is not known. We measured brain activity with functional magnetic resonance imaging in adults and 13-year-old children. Data were analyzed with an event-related design to isolate activity during cue, delay, distraction, and response selection. Adults were more accurate and less distractible than children. Activity in the middle frontal gyrus and intraparietal cortex was stronger in adults than in children during the delay, when information was maintained in WM. Distraction during the delay evoked activation in parietal and occipital cortices in both adults and children. However, distraction activated frontal cortex only in children. The larger frontal activation in response to distracters presented during the delay may explain why children are more susceptible to interfering stimuli.

Computerized training of working memory in children with ADHD--a randomized, controlled trial.

OBJECTIVE: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic practice of WM tasks. METHOD: Included in the trial were 53 children with ADHD (9 girls; 15 of 53 inattentive subtype), aged 7 to 12 years, without stimulant medication. The compliance criterion (>20 days of training) was met by 44 subjects, 42 of whom were also evaluated at follow-up 3 months later. Participants were randomly assigned to use either the treatment computer program for training WM or a comparison program. The main outcome measure was the span-board task, a visuospatial WM task that was not part of the training program. RESULTS: For the span-board task, there was a significant treatment effect both post-intervention and at follow-up. In addition, there were significant effects for secondary outcome tasks measuring verbal WM, response inhibition, and complex reasoning. Parent ratings showed significant reduction in symptoms of inattention and hyperactivity/impulsivity, both post-intervention and at follow-up. CONCLUSIONS: This study shows that WM can be improved by training in children with ADHD. This training also improved response inhibition and reasoning and resulted in a reduction of the parent-rated inattentive symptoms of ADHD.

Increased prefrontal and parietal activity after training of working memory.

Working memory capacity has traditionally been thought to be constant. Recent studies, however, suggest that working memory can be improved by training. In this study, we have investigated the changes in brain activity that are induced by working memory training. Two experiments were carried out in which healthy, adult human subjects practiced working memory tasks for 5 weeks. Brain activity was measured with functional magnetic resonance imaging (fMRI) before, during and after training. After training, brain activity that was related to working memory increased in the middle frontal gyrus and superior and inferior parietal cortices. The changes in cortical activity could be evidence of training-induced plasticity in the neural systems that underlie working memory.

Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network.

The aim of this study was to explore whether there are networks of regions where maturation of white matter and changes in brain activity show similar developmental trends during childhood. In a previous study, we showed that during childhood, grey matter activity increases in frontal and parietal regions. We hypothesized that this would be mediated by maturation of white matter. Twenty-three healthy children aged 8-18 years were investigated. Brain activity was measured using the blood oxygen level-dependent (BOLD) contrast with functional magnetic resonance imaging (fMRI) during performance of a working memory (WM) task. White matter microstructure was investigated using diffusion tensor imaging (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an indicator of myelination and axon thickness. Prior to scanning, WM score was evaluated. WM score correlated independently with FA values and BOLD response in several regions. FA values and BOLD response were extracted for each subject from the peak voxels of these regions. The FA values were used as covariates in an additional BOLD analysis to find brain regions where FA values and BOLD response correlated. Conversely, the BOLD response values were used as covariates in an additional FA analysis. In several cortical and sub-cortical regions, there were positive correlations between maturation of white matter and increased brain activity. Specifically, and consistent with our hypothesis, we found that FA values in fronto-parietal white matter correlated with BOLD response in closely located grey matter in the superior frontal sulcus and inferior parietal lobe, areas that could form a functional network underlying working memory function.