Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease.

AIM: To investigate the relationship between bone marrow fat content and hepatic fat content in children with known or suspected non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant, cross-sectional, prospective analysis of data collected between October 2010 to March 2013 in 125 children with known or suspected NAFLD. Written informed consent was obtained for same-day research magnetic resonance imaging (MRI) of the lumbar spine, liver, and abdominal adiposity. Lumbar spine bone marrow proton density fat fraction (PDFF) and hepatic PDFF were estimated using complex-based MRI (C-MRI) techniques and magnitude-based MRI (M-MRI), respectively. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) were quantified using high-resolution MRI. All images were acquired by two MRI technologists. Hepatic M-MRI images were analysed by an image analyst; all other images were analysed by a single investigator. The relationship between lumbar spine bone marrow PDFF and hepatic PDFF was assessed with and without adjusting for the presence of covariates using correlation and regression analysis. RESULTS: Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD prior to adjusting for covariates (r=0.33, p=0.0002). Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD (r=0.24, p=0.0079) after adjusting for age, sex, body mass index z-score, VAT, and SCAT in a multivariable regression analysis. CONCLUSION: Bone marrow fat content is positively associated with hepatic fat content in children with known or suspected NAFLD. Further research is needed to confirm these results and understand their clinical and biological implications.

Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders.

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.

The relative efficiency of time-to-threshold and rate of change in longitudinal data.

Randomized, placebo-controlled trials often use time-to-event as the primary endpoint, even when a continuous measure of disease severity is available. We compare the power to detect a treatment effect using either rate of change, as estimated by linear models of longitudinal continuous data, or time-to-event estimated by Cox proportional hazards models. We propose an analytic inflation factor for comparing the two types of analyses assuming that the time-to-event can be expressed as a time-to-threshold of the continuous measure. We conduct simulations based on a publicly available Alzheimer's disease data set in which the time-to-event is algorithmically defined based on a battery of assessments. A Cox proportional hazards model of the time-to-event endpoint is compared to a linear model of a single assessment from the battery. The simulations also explore the impact of baseline covariates in either analysis.

HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study.

OBJECTIVES: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). METHODS: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). RESULTS: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups). CONCLUSIONS: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization.

BACKGROUND: Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally. OBJECTIVE: To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures. METHODS: A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials. RESULTS: The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Abeta-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures. CONCLUSION: The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.

Quitting cigarettes completely or switching to smokeless tobacco: do US data replicate the Swedish results?

BACKGROUND: Swedish male smokers are more likely than female smokers to switch to smokeless tobacco (snus) and males' smoking cessation rate is higher than that of females. These results have fuelled international debate over promoting smokeless tobacco for harm reduction. This study examines whether similar results emerge in the United States, one of few other western countries where smokeless tobacco has long been widely available. METHODS: US DATA SOURCE: national sample in Tobacco Use Supplement to Current Population Survey, 2002, with 1-year follow-up in 2003. Analyses included adult self-respondents in this longitudinal sample (n = 15,056). Population-weighted rates of quitting smoking and switching to smokeless tobacco were computed for the 1-year period. RESULTS: Among US men, few current smokers switched to smokeless tobacco (0.3% in 12 months). Few former smokers turned to smokeless tobacco (1.7%). Switching between cigarettes and smokeless tobacco, infrequent among current tobacco users (<4%), was more often from smokeless to smoking. Men quit smokeless tobacco at three times the rate of quitting cigarettes (38.8% vs 11.6%, p<0.001). Overall, US men have no advantage over women in quitting smoking (11.7% vs 12.4%, p = 0.65), even though men are far likelier to use smokeless tobacco. CONCLUSION: The Swedish results are not replicated in the United States. Both male and female US smokers appear to have higher quit rates for smoking than have their Swedish counterparts, despite greater use of smokeless tobacco in Sweden. Promoting smokeless tobacco for harm reduction in countries with ongoing tobacco control programmes may not result in any positive population effect on smoking cessation.

Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study.

OBJECTIVE: This study examines the sex-specific associations of plasma concentrations of iron, copper, and zinc with cognitive function in older community-dwelling adults. DESIGN: Cross-sectional study. SETTING: 1988-92 follow-up clinic visit. PARTICIPANTS: 602 men and 849 women (average age=75 +/- 8 years) who were community-dwelling and not clinically demented. MEASUREMENTS: Blood samples were assayed for trace elements and 12 cognitive function tests were administered. Sex-specific analyses were adjusted for age, education, alcohol consumption, smoking, exercise, and estrogen use in women. RESULTS: Men and women differed significantly in education and alcohol intake (p's < 0.001), concentrations of plasma iron, copper and zinc (p's < 0.001) and scores on 11 of 12 cognitive function tests (p=0.04 to < 0.001). Regression analyses showed significant inverted U-shaped associations in men; both low and high iron levels were associated with poor performance on total and long-term recall and Serial 7's (p's=0.018, 0.042 and 0.004, respectively) compared to intermediate concentrations. In women, iron and copper concentrations had inverse linear associations with Buschke total, long and short-term recall and Blessed scores (p's < 0.05). Zinc was positively associated with performance on Blessed Items (p=0.008). Analyses comparing cognitive function using categorically defined mineral concentrations yielded similar sex specific results. CONCLUSION: Optimal trace element concentrations may exist for optimal cognitive function in older adults, and these levels may differ by sex and cognitive function domain.

Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment.

OBJECTIVE: To compare volumetric MRI of whole brain and medial temporal lobe structures to clinical measures for predicting progression from amnestic mild cognitive impairment (MCI) to Alzheimer disease (AD). METHODS: Baseline MRI scans from 129 subjects with amnestic MCI were obtained from participants in the Alzheimer's Disease Cooperative Study group's randomized, placebo-controlled clinical drug trial of donepezil, vitamin E, or placebo. Measures of whole brain, ventricular, hippocampal, and entorhinal cortex volumes were acquired. Participants were followed with clinical and cognitive evaluations until formal criteria for AD were met, or completion of 36 months of follow-up. Logistic regression modeling was done to assess the predictive value of all MRI measures, risk factors such as APOE genotype, age, family history of AD, education, sex, and cognitive test scores for progression to AD. Least angle regression modeling was used to determine which variables would produce an optimal predictive model, and whether adding MRI measures to a model with only clinical measures would improve predictive accuracy. RESULTS: Of the four MRI measures evaluated, only ventricular volumes and hippocampal volumes were predictive of progression to AD. Maximal predictive accuracy using only MRI measures was obtained by hippocampal volumes by themselves (60.4%). When clinical variables were added to the model, the predictive accuracy increased to 78.8%. Use of MRI measures did not improve predictive accuracy beyond that obtained by cognitive measures alone. APOE status, MRI, or demographic variables were not necessary for the optimal predictive model. This optimal model included the Delayed 10-word list recall, New York University Delayed Paragraph Recall, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. CONCLUSION: In moderate stages of amnestic mild cognitive impairment, common cognitive tests provide better predictive accuracy than measures of whole brain, ventricular, entorhinal cortex, or hippocampal volumes for assessing progression to Alzheimer disease.

Cycad exposure and risk of dementia, MCI, and PDC in the Chamorro population of Guam.

OBJECTIVE: To study cycad-derived products as possible risk factors for dementia, mild cognitive impairment (MCI), and parkinsonism-dementia complex (PDC) on Guam. METHODS: Complete risk factor data from in-person interviews of 166 cases of Guam dementia, 50 cases of amnestic MCI, and 21 cases of PDC were compared with 1,581 controls in the base population regarding exposure to cycad-derived products from a traditional food (fadang), consumption of fruit bats, and use of cycad-derived topical medicine. RESULTS: Adjusted odds ratios (ORs) and 95% CIs for picking, processing, and eating fadang in young adulthood ranged from 1.42 (1.05 to 1.91) to 2.87 (1.48 to 5.56) and were consistently elevated and significant across all three diagnostic outcomes. Associations independent of exposure in young adulthood were for picking (OR 0.78, 95% CI 0.64 to 0.96) and processing (OR 0.77, 95% CI 0.63 to 0.94) fadang in childhood with Guam dementia. Men showed stronger and more consistent relations across exposure groups in young adulthood compared with women. No associations were found for consumption of fruit bats or exposure to cycad used as a topical medicine for any of the outcomes. Estimated adjusted population attributable risks suggest that exposure to eating fadang in young adulthood incurred the highest attributable risk percent. CONCLUSIONS: Environmental lifestyle and diet may contribute to the etiology of neurodegenerative diseases in the native population of Guam.

Prevalence of dementia in Chamorros on Guam: relationship to age, gender, education, and APOE.

OBJECTIVES: To estimate the prevalence of dementia and its clinical subtypes among Chamorros on Guam aged 65 years or older and to examine associations with age, gender, education, and APOE genotype. BACKGROUND: Chamorros, the indigenous people of Guam, had a high incidence of ALS and parkinsonism-dementia complex (PDC), in the 1950s. Over the next 50 years, ALS incidence declined markedly, but PDC only slightly. The prevalence of late life dementia in Chamorros and its relationship to ALS/PDC are unknown. METHODS: Island-wide population-based survey of Chamorros aged 65 years or older as of January 1, 2003. Two-stage assessment: cognitive and motor screening, followed by neurologic and psychometric evaluation. Data were reviewed at consensus conference to make clinical diagnoses. RESULTS: Of 2,789 Chamorros aged 65 years or older, 73% were enrolled; 27% declined participation, died before contact or screening, or moved off Guam. The point prevalence of all-cause dementia on February 1, 2004, was 12.2%. Prevalence data for subtypes were as follows: Guam dementia (clinically equivalent to AD), 8.8%; PDC, 1.5%; pure vascular dementia, 1.3%; other, 0.6%. The prevalence of dementia rose exponentially with age. Low education was significantly associated with dementia, but gender was not. There was a trend toward higher PDC prevalence among men. The APOE epsilon4 allele was not associated with dementia. CONCLUSIONS: The prevalence of dementia among elderly Chamorros is relatively high. Guam dementia is the most common diagnosis and exceeds parkinsonism-dementia complex. Age and low education are strongly associated with dementia, but gender and APOE epsilon4 are not. Incidence studies will allow risk factors for dementia to be clarified.

Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment.

OBJECTIVE: To investigate the neurocognitive measures that best predict progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). METHODS: We evaluated 539 participants with aMCI from the Alzheimer's Disease Cooperative Study clinical drug trial of donepezil, vitamin E, or placebo. During the study period of 36 months, 212 aMCI participants progressed to AD. Using progression from aMCI to AD within 36 months as the dependent variable, a generalized linear model was fit to the data using the least absolute shrinkage and selection operator. Independent variables included in this analysis were age, sex, education, APOE-e4 (APOE4) status, family history of dementia, Mini-Mental State Examination score, Digits Backwards (Wechsler Memory Scale), Maze Time and Errors, Number Cancellation, Delayed Recall of Alzheimer's Disease Assessment Scale Word List, New York University Paragraph Recall Test (Immediate and Delayed), Boston Naming Test, Category Fluency, Clock Drawing Test, and the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog). RESULTS: The model that best predicted progression from aMCI to AD over 36 months included APOE4 status, the Symbol Digit Modalities Test, Delayed 10-Word List Recall, New York University Paragraph Recall Test (Delayed), and the ADAS-cog total score. When APOE4 was removed from the analysis the resulting model had a similar estimated predictive accuracy as the full model. As determined by cross-validation, the estimated predictive accuracy of the final model was 80%. CONCLUSION: Progression from amnestic mild cognitive impairment to Alzheimer disease in this cohort was best determined by combining four common, easily administered, cognitive measures.

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Alzheimer disease without neocortical neurofibrillary tangles: "a second look".

OBJECTIVE: To compare the clinical and pathologic features of plaque only Alzheimer disease (POAD) with plaque and tangle Alzheimer disease (PTAD). METHODS: An autopsy series of 16 patients with POAD and 32 subjects with PTAD on whom extensive antemortem neuropsychological testing was available. Plaques, tangles, and cerebral amyloid angiopathy were examined in the neocortex and hippocampus using thioflavin S staining. In addition, immunocytochemical analysis with AT8 for phosphorylated tau was performed. Midfrontal (MF) synaptic density, MF choline acetyltransferase (ChAT) activity, and apolipoprotein E genotyping were also assessed. RESULTS: Initial neuropsychological test scores and rates of cognitive decline on the Mini-Mental State Examination and Blessed Information-Memory-Concentration were similar between the two groups. However, compared to PTAD, POAD patients tended to deteriorate more slowly on the Mattis Dementia Rating Scale. Furthermore, they were somewhat less impaired on all these measures at last examination. There was an older age at onset and death, and a trend toward a shorter disease duration, in POAD compared to PTAD patients. POAD subjects, by definition, had no neocortical neurofibrillary tangles (NFT) (Braak stages IV or less). In addition, they also had fewer hippocampal NFT, fewer neuritic plaques, and higher mean MF ChAT activity than PTAD subjects. On the other hand, the two groups did not differ significantly in brain weight or MF synaptic density. Although lacking overt tangle formation, the POAD group displayed abnormal phosphorylated tau immunoreactivity in neocortical pyramidal neurons. CONCLUSIONS: Dementing syndromes virtually indistinguishable from each other can, and do, develop in the presence or absence of neocortical NFT. Patients without neocortical NFT are, on average, older at disease onset and death, and show a trend toward a shorter disease duration with somewhat slower deterioration. Although neocortical NFT per se are not obligatory for the development of clinical dementia, more subtle neocortical cytoskeletal tau pathology may contribute to cognitive decline in these subjects.

Behavioural abnormalities contribute to functional decline in Huntington's disease.

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.

ALS and PDC of Guam: forty-year follow-up.

BACKGROUND: It was noticed in the mid-1950s that the incidence of ALS and parkinsonism--dementia complex (PDC) were much higher on Guam than anywhere else in the world. In 1958, a registry of patients and controls was established to ascertain the familial and genetic aspects of these diseases. Patients and individually matched controls and their relatives were registered from 1958 to 1963. The registry was updated and analyzed in 1998 through 1999. OBJECTIVE: To ascertain whether first-degree relatives of patients had a higher risk for developing ALS or PDC than relatives of controls. METHODS: During the period of 1958 to 1963, 126 new patients and 126 individually matched controls and their respective first-degree relatives and spouses were evaluated neurologically and registered. Forty years later, the number of new cases among the patient and control relatives were compared to an expected number of new cases based on the age- and sex-specific incidence of ALS and PDC in the population at large. RESULTS: From 1958 to 1999, there were 102 new ALS or PDC cases among relatives of patients and 33 among relatives of controls. These values were compared with the derived expected values. There were more observed than expected new cases among patients' relatives, and less observed cases than expected among the controls' relatives. CONCLUSIONS: Relatives of patients with ALS or PDC have significantly higher risks for developing the disease than the Guamanian population, whereas relatives of controls have significantly lower risks.

Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration.

OBJECTIVE: To examine (1) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration (AMD) and (2) the relationship in this population between depression, visual acuity, the number of comorbid medical conditions, disability caused by vision loss as measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision-specific Sickness Impact Profile (SIPV), and disability caused by overall health status as measured by the Sickness Impact Profile-68 (SIP). DESIGN: Analysis of cross-sectional baseline data from a randomized clinical trial. PARTICIPANTS: Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced macular degeneration whose vision was 20/60 or worse in their better eye. METHODS: Subjects were interviewed using measures of depression, disability, and chronic medical conditions. Visual acuity was obtained. Nonparametric correlation analyses and linear regression analyses were performed. MAIN OUTCOME MEASURES: Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP. RESULTS: Of the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder, twice the rate observed in previous studies of community-dwelling elderly. Over and above depression (GDS), visual acuity aided in prediction of the level of vision-specific disability (NEI-VFQ and SIPV). CONCLUSIONS: Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration. Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning. Over and above depression, visual acuity aided in predicting vision-specific disability. Treatment strategies that teach patients to cope with vision loss should be developed and evaluated.

Frequency of behavioral symptoms characterizes agitation in Alzheimer's disease.

This study describes two well-characterized groups of Alzheimer's disease (AD) patients with similar levels of cognitive functioning, but with different overall behavioral disturbance levels. We sought to determine the nature of this difference-whether AD patients with higher levels of behavioral disturbance (n = 148) differ from less disturbed AD patients (n = 235) in terms of (a) the range of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c) both of these. We defined and operationalized 'diversity of behaviors' and 'frequency' with respect to the item-level responses on the Cohen-Mansfield agitation inventory (CMAI). We found that, in these two samples of AD patients, differences occurred in the frequency of 10 out of 21 behaviors, rather than in a variety of endorsed behaviors. These 10 behaviors, observed at different frequencies in both groups, may be useful for monitoring change in studies of drugs or behavioral interventions for behavioral disturbance in persons with AD.

Effects of age on tissues and regions of the cerebrum and cerebellum.

Normal volunteers, aged 30 to 99 years, were studied with MRI. Age was related to estimated volumes of: gray matter, white matter, and CSF of the cerebrum and cerebellum; gray matter, white matter, white matter abnormality, and CSF within each cerebral lobe; and gray matter of eight subcortical structures. The results were: 1) Age-related losses in the hippocampus were significantly accelerated relative to gray matter losses elsewhere in the brain. 2) Among the cerebral lobes, the frontal lobes were disproportionately affected by cortical volume loss and increased white matter abnormality. 3) Loss of cerebral and cerebellar white matter occurred later than, but was ultimately greater than, loss of gray matter. It is estimated that between the ages of 30 and 90 volume loss averages 14% in the cerebral cortex, 35% in the hippocampus, and 26% in the cerebral white matter. Separate analyses were conducted in which genetic risk associated with the Apolipoprotein E epsilon4 allele was either overrepresented or underrepresented among elderly participants. Accelerated loss of hippocampal volume was observed with both analyses and thus does not appear to be due to the presence of at-risk subjects. MR signal alterations in the tissues of older individuals pose challenges to the validity of current methods of tissue segmentation, and should be considered in the interpretation of the results.

Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging.

Quantitative measurements of regional and tissue specific concentrations of brain metabolites were measured in elderly subjects using multislice proton magnetic resonance spectroscopic imaging ((1)H MRSI). Selective k-space extrapolation and an inversion-recovery sequence were used to minimize lipid contamination and linear regression was used to account for partial volume problems. The technique was applied to measure the concentrations of N-acetyl aspartate (NAA), and creatine (Cr)- and choline (Cho)-containing compounds in cortical gray and white matter, and white matter lesions of the frontal and the parietal lobe in 40 normal elderly subjects (22 females and 18 males, 56-89 years old, mean age 74 +/- 8). NAA was about 15% lower in cortical gray matter and 23% lower in white matter lesions when compared to normal white matter. Cr was 11% higher in cortical gray matter than in white matter, and also about 15% higher in the parietal cortex than in the frontal cortex. Cho was 28% lower in cortical gray matter than in white matter. Furthermore, NAA and Cr changes correlated with age. In conclusion, regional and tissue differences of brain metabolites must be considered in addition to age-related changes when interpreting (1)H MRSI data.

Brain dysmorphology in individuals with severe prenatal alcohol exposure.

Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia.