Longitudinal alcohol-related brain changes in older adults: The Sydney Memory and Ageing Study.

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.

Prospective Memory Function Predicts Future Cognitive Decline and Incident Dementia.

OBJECTIVES: This study aimed to test whether prospective memory (PM) was an early cognitive marker of future cognitive decline and incident dementia using longitudinal data spanning 8 years from the Sydney Memory and Ageing Study. METHODS: At baseline, 121 participants aged 72-91 years were tested in PM using a validated PM task, Virtual Week, which included time- and event-based tasks presented with varying regularity. Responses were scored "Correct" if completed accurately and "Missed" if the target was not remembered at any time. Measures of cognition were taken at baseline and 2-year intervals over 8 years. Dementia diagnoses were made by expert consensus panels using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Linear mixed models and Cox proportional hazards regression models were used to analyze the data, controlling for potential confounds. RESULTS: Both decreased PM accuracy and missed PM responses were associated with rate of cognitive decline measured by Mini-Mental State Examination over 8 years and global cognitive decline over 4 years. Risk of incident dementia increased with poorer baseline PM ability and missed responses. These effects remained significant after controlling for baseline cognition and were strongest for event-based and regular PM tasks. DISCUSSION: PM is a sensitive early marker of future cognitive decline and risk of incident dementia. PM tasks supported by spontaneous retrieval (event-based) and those with lower retrospective memory demands (regular tasks) function as particularly sensitive predictors. In other words, deficits in performing less effortful PM tasks best predicted cognitive decline. These findings may encourage clinicians to incorporate PM tasks in clinical assessments.

Collaboration and prospective memory: comparing nominal and collaborative group performance in strangers and couples.

To perform prospective memory (PM) tasks in day-to-day life, we often enlist the help of others. Yet the effects of collaboration on PM are largely unknown. Adopting the methodology of the "collaborative recall paradigm", we tested whether stranger dyads (Experiment 1) and intimate couples (Experiment 2) would perform better on a "Virtual Week" task when working together or each working separately. In Experiment 1, we found evidence of collaborative inhibition: collaborating strangers did not perform to their pooled individual potential, although the effect was modulated by PM task difficulty. We also found that the overall collaborative inhibition effect was attributable to both the retrospective and prospective components of PM. In Experiment 2 however, there was no collaborative inhibition: there was no significant difference in performance between couples working together or separately. Our findings suggest potential costs of collaboration to PM. Intimate relationships may reduce the usual costs of collaboration, with implications for intervention training programmes and for populations who most need PM support.

Temporal and mosaic Tsc1 deletion in the developing thalamus disrupts thalamocortical circuitry, neural function, and behavior.

Tuberous sclerosis is a developmental genetic disorder caused by mutations in TSC1, which results in epilepsy, autism, and intellectual disability. The cause of these neurological deficits remains unresolved. Imaging studies suggest that the thalamus may be affected in tuberous sclerosis patients, but this has not been experimentally interrogated. We hypothesized that thalamic deletion of Tsc1 at distinct stages of mouse brain development would produce differential phenotypes. We show that mosaic Tsc1 deletion within thalamic precursors at embryonic day (E) 12.5 disrupts thalamic circuitry and alters neuronal physiology. Tsc1 deletion at this early stage is unique in causing both seizures and compulsive grooming in adult mice. In contrast, only a subset of these phenotypes occurs when thalamic Tsc1 is deleted at a later embryonic stage. Our findings demonstrate that abnormalities in a discrete population of neurons can cause global brain dysfunction and that phenotype severity depends on developmental timing and degree of genetic mosaicism.

Warfarin therapy for livedoid vasculopathy associated with cryofibrinogenemia and hyperhomocysteinemia.

BACKGROUND: Livedoid vasculopathy is an idiopathic, chronic disorder manifested by painful, purpuric macules on the lower extremities that superficially ulcerate, resulting in atrophic, stellate scars with peripheral telangiectasias and hyperpigmentation. OBSERVATIONS: A 50-year-old man presented with recurrent, painful ulcerations on the medial aspect of his malleoli and calves. The clinical presentation, histologic findings, and results of laboratory evaluation confirmed the diagnosis of livedoid vasculopathy in this case. Despite being refractory to treatment with multiple other medications, the lesions responded dramatically to oral warfarin sodium therapy. CONCLUSION: Treatment with warfarin may be a beneficial therapy for patients with livedoid vasculopathy.

Home cage observations following acute and repeated IV cocaine in intact and gonadectomized rats.

The purpose of the present experiment was to examine the effects of acute and repeated intravenous (IV) cocaine on rat behavior in the home cage environment. An observational sampling method was used. Pair-housed, male, female, castrated (CAST), and ovariectomized (OVX) rats were administered daily IV cocaine injections (3.0 mg/kg/injection) in the home cage for 13 consecutive days, and observations occurred after the 1st and 13th injections. The incidence, i.e., occurrence or nonoccurrence of a behavior, was recorded according to a behavioral profile comprised of 11 behaviors. Data were analyzed as locomotor composite and orofacial composite scores. Behaviors not amenable for combination into a composite incidence score were evaluated independently (e.g., still behavior). Females exhibited more locomotor incidence scores than males following acute injection and more still behavior after repeated cocaine administration. Females exhibited more locomotor activity than OVX rats following acute, but not repeated, cocaine injection. There were no differences between the male and CAST rats on days 1 or 13. CAST rats exhibited more still behavior than OVX following only acute cocaine administration. This study indicates that IV cocaine-induced sex differences and the effects of gonadectomy can be measured in the home cage, and furthermore, describes a simple method to screen changes in cocaine-induced locomotor behaviors in the absence of automated equipment.

Acute and repeated intravenous cocaine-induced locomotor activity is altered as a function of sex and gonadectomy.

The present experiment examined the effects of sex and gonadectomy on cocaine-induced locomotor activity via intravenous (IV) cocaine. Male, female, castrated (CAST), and ovariectomized (OVX) rats received daily IV cocaine injections (3.0 mg/kg/injection) for 13 consecutive days. Locomotor activity was measured in automated activity chambers for 60 min following the baseline-saline administration and after the 1st and 13th cocaine injections. Observational time sampling was also performed, and the observational data were grouped into locomotor and orofacial composite incidence scores. Females exhibited more cocaine-induced locomotor activity, rearing, and locomotor incidence compared to males. The orofacial data revealed a sex difference in the expression of behavioral sensitization: females exhibited more orofacial behaviors than males after repeated, but not acute, cocaine injection. Females exhibited more cocaine-induced locomotor activity, rearing, and locomotor incidence compared to OVX rats, but exhibited less orofacial incidence following acute cocaine administration. There were no differences between male and CAST rats. CAST rats showed more locomotor incidence than OVX after repeated, but not acute, cocaine injection. CAST rats exhibited behavioral sensitization, whereas OVX rats' locomotor incidence did not change with repeated cocaine injection. CAST rats showed less orofacial incidence than OVX after acute, but not repeated, cocaine injection. These findings demonstrate sex differences in response to IV cocaine and replicate earlier findings which show that OVX attenuates increased locomotor activity in females. Furthermore, these findings suggest that IV cocaine administration produces behavioral differences between male and female rats in the absence of circulating gonadal hormones.

Thalidomide in the treatment of recalcitrant Sweet's syndrome associated with myelodysplasia.

Sweet's syndrome is a neutrophilic dermatosis characterized by tender, erythematous, pseudovesicular plaques that can be associated with hematologic malignancy. We report a patient with recalcitrant Sweet's syndrome that preceded the development of myelodysplastic syndrome by 30 months. The delay between the onset of Sweet's syndrome and the subsequent diagnosis of myelodysplasia highlights the need for thorough and repeated evaluation for underlying malignancy in patients with such a course. Although corticosteroids are the initial treatment of choice, this patient's eruption was only partially responsive to high-dose prednisone and was refractory to metronidazole, dapsone, and methotrexate. Treatment with thalidomide resulted in complete resolution of the cutaneous lesions within one month of therapy.

Telephone social support for low-income pregnant women.

OBJECTIVE: To assess whether social support can be provided to low-income pregnant women by telephone. DESIGN: A qualitative pilot study. SETTING: Nonurban prenatal clinics. PARTICIPANTS: Convenience sample of 20 pregnant women who were eligible for Medicaid, spoke English, were at least 24 weeks gestation, and had a telephone or access to a telephone. RESULTS: The Baby-Beep pilot program provides strong evidence that a telephone social support intervention is feasible and highly acceptable to a group of low-income pregnant women. Through the use of the telephone, a strong rapport appeared to develop between the health care provider and the women because nonverbal cues were eliminated. The study also found that collaboration between mental health nurses and prenatal care providers could help create safe, cost-effective psychosocial care for pregnant women. CONCLUSION: The Baby-Beep pilot study provides important information about one way to deliver social support to low-income women who may have little or no social support and feel alienated in a clinical setting.