ABSTRACT
RATIONALE: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-D-aspartate (NMDA) receptor function. OBJECTIVES: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. METHODS: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. RESULTS: No group performance differences were observed on placebo for Go correct hit or No-Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. CONCLUSIONS: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group.
Subject(s)
Alcoholism/epidemiology , Excitatory Amino Acid Antagonists/pharmacology , Family Health , Memantine/pharmacology , Adolescent , Adult , Caudate Nucleus/metabolism , Double-Blind Method , Excitatory Amino Acid Antagonists/administration & dosage , Female , Gyrus Cinguli/metabolism , Humans , Impulsive Behavior/epidemiology , Inhibition, Psychological , Magnetic Resonance Imaging/methods , Male , Memantine/administration & dosage , Young AdultABSTRACT
BACKGROUND - Idiopathic normal pressure hydrocephalus (iNPH) is a reversible dementia in which fronto-striatal cognitive deficits and apathy may be present. OBJECTIVES - The study investigated structural volumetric changes in iNPH, apart from ventriculomegaly. MATERIALS AND METHODS - A full-brain voxel-based morphometric analysis between 11 iNPH patients and 14 healthy controls identified regions of interest (ROIs) for manual volumetric analyses. RESULTS - Caudate and corpus callosum ROI measurements revealed diminished caudate nuclei volume in the iNPH group. CONCLUSIONS - The role of the caudate nucleus in cognitive and affective changes in iNPH should now be explored.
Subject(s)
Atrophy/pathology , Basal Ganglia Diseases/etiology , Basal Ganglia Diseases/pathology , Caudate Nucleus/pathology , Hydrocephalus, Normal Pressure/complications , Hydrocephalus, Normal Pressure/pathology , Aged , Aged, 80 and over , Atrophy/physiopathology , Basal Ganglia Diseases/physiopathology , Caudate Nucleus/physiopathology , Cerebrospinal Fluid Pressure/physiology , Corpus Callosum/pathology , Corpus Callosum/physiopathology , Disease Progression , Female , Humans , Hydrocephalus, Normal Pressure/physiopathology , Image Processing, Computer-Assisted , Intracranial Hypertension/complications , Intracranial Hypertension/pathology , Intracranial Hypertension/physiopathology , Lateral Ventricles/pathology , Lateral Ventricles/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of TestsABSTRACT
Normal pressure hydrocephalus (NPH) accounts for one of the few known forms of reversible dementia. Varied aetiology and clinical presentation contribute to difficulties with early or differential diagnoses, and delayed surgical treatment may be less efficacious. Clinical neuropsychology provides a means of determining a cognitive profile for NPH, assisting in differential diagnosis, tracking the disorder's progression and assessing the efficacy of treatment. This article will review possible applications of clinical neuropsychology and propose a clinical assessment protocol for NPH.
