Derek Flenniken

Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites.

BACKGROUND The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern. METHODS Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short-echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing. RESULTS Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non-binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes. CONCLUSIONS Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.

Heavy alcohol consumption in individuals with HIV infection: Effects on neuropsychological performance

Higher rates of alcohol use have been reported in HIV+ individuals compared to the general population. Both heavy alcohol use and HIV infection are associated with increased risk of neuropsychological (NP) impairment. We examined effects of heavy active alcohol use and HIV on NP functioning in a large sample of community-residing HIV+ individuals and HIV- controls. The four main study groups included 72 HIV- light/non-drinkers, 70 HIV- heavy drinkers (>100 drinks per month), 70 HIV+ light/non-drinkers, and 56 HIV+ heavy drinkers. The heavy drinking group was further subdivided to assess effects of the heaviest levels of active alcohol use (>6 drinks per day) on NP functioning. A comprehensive NP battery was administered. Multivariate analysis of covariance was employed to examine the effect of HIV and alcohol on NP functioning after adjusting for group differences in age and estimated premorbid verbal intellectual functioning. The analyses identified main effects of heavy drinking and HIV on NP function, with greatest effects involving the contrast of HIV+ heavy drinkers and the HIV- light drinkers. Synergistic effects of heaviest current drinking and HIV infection were identified in analyses of motor and visuomotor speed. Supplementary analyses also revealed better NP function in the HIV+ group with antiretroviral treatment (ART) and lower level of viral burden, a finding that was consistent across levels of alcohol consumption. Finally, heavy alcohol use and executive functioning difficulties were associated with lower levels of self-reported medication adherence in the HIV+ group. The findings suggest that active heavy alcohol use and HIV infection have additive adverse effects on NP function, that they may show synergistic effects in circumstances of very heavy active alcohol use, and that heavy drinking and executive functioning may mediate health-related behaviors in HIV disease.

Identification of Abnormal Neuronal Metabolism Outside the Seizure Focus in Temporal Lobe Epilepsy

Summary:  Purpose: The aim of this study was to identify metabolically abnormal extrahippocampal brain regions in patients with temporal lobe epilepsy with (TLE‐MTS) and without (TLE‐no) magnetic resonance imaging (MRI) evidence for mesial‐temporal sclerosis (MTS) and to assess their value for focus lateralization by using multislice 1H magnetic resonance spectroscopic imaging (MRSI).

Reduced extrahippocampal NAA in mesial temporal lobe epilepsy.

Summary:  Purpose: Structural and metabolic abnormalities in the hippocampal region in medial temporal lobe epilepsy (mTLE) are well described; less is known about extrahippocampal changes. This study was designed to characterize extrahippocampal metabolic abnormalities in mTLE with magnetic resonance spectroscopy in combination with tissue segmentation and volumetry of gray and white matter.

Spectroscopic metabolic abnormalities in mTLE with and without MRI evidence for mesial temporal sclerosis using hippocampal short-TE MRSI

Summary:  Purpose: Long echo time (TE) spectroscopy reliably identifies the epileptogenic hippocampus in mesial temporal lobe epilepsy. Short‐TE spectroscopy gives additional metabolic information but may have more artifacts. The aim of this study was to test (a) lateralization of the seizure focus by short‐TE spectroscopy, and (b) value of myoinositol (MI) in the identification of the epileptogenic hippocampus.

ERP evidence of impaired central nervous system function in virally suppressed HIV patients on antiretroviral therapy.

OBJECTIVE To examine the effects of human immunodeficiency virus (HIV) on central nervous system (CNS) function in patients receiving antiretroviral therapy (ART) who have suppressed viral loads. METHODS Event-related brain potentials (ERPs) were recorded from 15 virally suppressed HIV patients and 15 age-, sex-, and education-matched controls while they performed a 3-stimulus auditory oddball task. The amplitude and latency of the P3a, P3b, and early auditory components were examined in HIV patients and controls. RESULTS Virally suppressed HIV patients on ART were more depressed than controls, as determined by the Beck Depression Inventory (BDI). After controlling for the effects of depression, HIV patients had smaller P2, P3a, and P3b amplitudes and longer P3a and P3b latency than control subjects. BDI scores correlated positively with N1 latency in HIV patients and negatively with P3b amplitude in all subjects. CONCLUSIONS These electrophysiological results suggest that, even in the absence of detectable levels of HIV in the peripheral blood, viral replication persists in the CNS and continues to cause disease in HIV patients on ART.

Metabolic characteristics of cortical malformations causing epilepsy

AbstractPurposeCortical malformations (CMs) are increasingly recognized as the epileptogenic substrate in patients with medically refractory neocortical epilepsy (NE). The aim of this study was to test the hypotheses that: 1. CMs are metabolically heterogeneous. 2. The structurally normal appearing perilesional zone is characterized by similar metabolic abnormalities as the CM.MethodsMagnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation was performed on eight patients with NE and CMs and 19 agematched controls. In controls, NAA, Cr, Cho,NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed as a function of white matter content and thresholds for pathological values determined by calculating the 95% prediction intervals. These thresholds were used to identify metabolically abnormal voxels within the CM and in the perilesional zone.Results30% of all voxels in the CMs were abnormal, most frequently because of decreases of NAA or increases of Cho. Abnormal voxels tended to form metabolically heterogeneous clusters interspersed in metabolically normal regions. Furthermore, 15% of all voxels in the perilesional zone were abnormal, the most frequent being decreases of NAA and Cr.ConclusionIn CMs metabolically normal regions are interspersed with metabolically heterogeneous abnormal regions. Metabolic abnormalities in the perilesional zone share several characteristics of CMs and might therefore represent areas with microscopic malformations and/or intrinsic epileptogenicity.

Identification of the epileptogenic lobe in neocortical epilepsy with proton MR spectroscopic imaging.

Summary:  Purpose: The aim of this study was to evaluate the usefulness of multislice magnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation for the identification of the epileptogenic focus in neocortical epilepsy (NE).

Total Sleep Time Interacts With Age to Predict Cognitive Performance Among Adults

STUDY OBJECTIVES To investigate interactions between high and low amounts of sleep and other predictors of cognitive performance. METHODS We used four cognitive tests to determine whether sleep time interacted with age, personal history of a memory problem, parental history of a memory problem, or personal concerns about memory and were associated with cognitive performance. Data were collected from an internet-based cohort study. We used an ordinary least squares regression with restricted cubic splines, controlling for demographic variables and comorbidities. RESULTS We found significant nonlinear interactions between (1) total sleep time and age and (2) total sleep time and personal history of a memory problem and cognitive performance. Short and long sleep durations and self-reported memory complaints were associated with poorer performance on a test of attention and this was true to a greater degree in younger and older adults. A repeat analysis excluding subjects reporting dementia was significant only for the test of attention. CONCLUSIONS These results extend existing data on sleep duration and cognition across the lifespan by combining in a single study the results from four specific cognitive tests, both younger and older adults, and four self-reported risk factors for cognitive impairment. Longitudinal studies with biomarkers should be undertaken to determine whether causal mechanisms, such as inflammation or amyloid buildup, account for these associations.

VALIDATION OF ONLINE DATA FROM IDEAS PARTICIPANTS WITH MCI AND AD USING THE BRAIN HEALTH REGISTRY

amyloid PET were better with in-clinic memory measures (0.360.61) than ARC Prices (0.31), a composite of ARC measures showed stronger correlations with both CSF tau (ARC 1⁄4 0.64 vs. in-clinic 1⁄4 0.25; Figure 2) and tau PET (ARC 1⁄4 0.41 vs. in-clinic 1⁄4 0.16). Conclusions: Extremely brief and frequent smartphone cognitive assessments demonstrate excellent reliability and are valid measures of cognition that are sensitive to AD biomarkers. These measures may be particularly sensitive to neurodegeneration in preclinical AD populations. Correlations between cerebrospinal fluid total-tau and ARC smartphone assessments and standard in-clinic assessments (n 1⁄4 30).