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R A Sperling

Publications and source records attributed to R A Sperling.

10 recordsLinked to original sources
PubMed2005

Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD.

OBJECTIVE: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). METHODS: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. RESULTS: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE epsilon4 allele than in the 16 noncarriers. CONCLUSIONS: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.

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PubMed2003

fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease.

OBJECTIVE: To examine alterations in patterns of brain activation seen in normal aging and in mild Alzheimer's disease by functional magnetic resonance imaging (fMRI) during an associative encoding task. METHODS: 10 young controls, 10 elderly controls, and seven patients with mild Alzheimer's disease were studied using fMRI during a face-name association encoding task. The fMRI paradigm used a block design with three conditions: novel face-name pairs, repeated face-name pairs, and visual fixation. RESULTS: The young and elderly controls differed primarily in the pattern of activation seen in prefrontal and parietal cortices: elderly controls showed significantly less activation in both superior and inferior prefrontal cortices but greater activation in parietal regions than younger controls during the encoding of novel face-name pairs. Compared with elderly controls, the Alzheimer patients showed significantly less activation in the hippocampal formation but greater activation in the medial parietal and posterior cingulate regions. CONCLUSIONS: The pattern of fMRI activation during the encoding of novel associations is differentially altered in the early stages of Alzheimer's disease compared with normal aging.

Adult↗
PubMed2001

Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis: a longitudinal study.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period. DESIGN: Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses. RESULTS: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level-matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001). CONCLUSIONS: Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.

Adult↗
PubMed2001

Encoding novel face-name associations: a functional MRI study.

The process of forming new associations between previously unrelated items of information, such as a name and a face, likely requires the integration of activity within multiple brain regions. The hippocampus and related structures in the medial temporal lobe are thought to be particularly critical in binding together items of information. We studied eight healthy young subjects with functional magnetic resonance imaging (fMRI) during the encoding of novel face-name associations compared to viewing repeated face-name pairs. A consistent pattern of activation was observed in the hippocampus, pulvinar nucleus of the thalamus, fusiform and dorsolateral prefrontal cortices across individual subjects. The location of the activation within the hippocampus was more anterior than previously reported in studies using similar novel vs. repeated paradigms with stimuli that did not specifically require relational processing among unrelated items. These data suggest that the process of forming new face-name associations is supported by a distributed network of brain regions, and provide additional evidence for the essential role of the hippocampus in associative memory processes.

Adult↗
PubMed2000

Donepezil therapy in clinical practice: a randomized crossover study.

OBJECTIVE: To determine the efficacy of donepezil hydrochloride for the treatment of Alzheimer disease in patients drawn from clinical practice. DESIGN: Two-center, randomized, placebo-controlled, double-masked crossover study. SETTING: Memory disorders units at Massachusetts General and Brigham and Women's hospitals, Boston. PATIENTS: Sixty individuals (30 men and 30 women; mean +/- SD age, 75.0+/-9.5 years) with probable Alzheimer disease and scores of 20 or less on the information-memory-concentration subscale of the Blessed Dementia Scale. INTERVENTIONS: Placebo wash-in, followed in randomized sequence by (1) donepezil hydrochloride therapy, 5 mg/d, for 6 weeks, followed by placebo washout for 6 weeks and (2) placebo treatment for 6 weeks. PRIMARY OUTCOME MEASURE: Change in Alzheimer's Disease Assessment Scale cognitive subscale scores from the beginning to the end of the two 6-week treatment periods. RESULTS: Among patients completing treatment and testing for both periods (n = 48), subscale scores improved (mean +/- SEM) 2.17+/-0.98 points (95% confidence interval, 0.20-4.10 points) during donepezil therapy relative to placebo therapy (P = .04). Scores returned toward baseline within 3 weeks of drug washout. There was no associated change in caregiver-rated global impression (donepezil vs placebo: proportion improved, 0.24 vs 0.22; proportion worsened, 0.27 vs 0.35; P = .34) or on specific tests of explicit memory or verbal fluency. Contrary to studies with tacrine, the presence of the apolipoprotein E epsilon4 allele did not predict donepezil treatment failure. Most common adverse events related to donepezil therapy were nausea (5 patients), diarrhea (3 patients), and agitation (3 patients). Serious events possibly related to drug use were seizure, pancreatitis, and syncope (1 patient each). CONCLUSION: This independent confirmation of data from phase 3 trials suggests that donepezil therapy modestly improves cognition in patients with Alzheimer disease who are encountered in clinical practice.

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PubMed1997

Extensive reversible brain magnetic resonance lesions in a patient with HELLP syndrome.

A severe form of toxemia of pregnancy with microangiopathic hemolytic anemia, elevated liver enzymes, and low platelets has been called the HELLP syndrome. A patient with the HELLP syndrome developed a severe, reversible encephalopathy. Brain computed tomography and magnetic resonance imaging showed abnormalities consistent with edema limited to the posterior circulation territory. The location of the lesions and their occurrence in the HELLP syndrome support suggestions that the vulnerability of posterior structures in eclamptic encephalopathy is due to a vascular susceptibility of the posterior circulation and that endothelial cell dysfunction plays an important role in the pathogenesis of eclamptic encephalopathy.

Adult↗
PubMed1996

Noninvasive perfusion MRI in Alzheimer's disease: a preliminary report.

We performed functional MRI using the echo-planar imaging and signal targeting with alternating radio frequency (EPISTAR) technique in 11 patients with Alzheimer's disease (AD) and 8 age-matched control subjects. Seven of the AD patients had qualitatively apparent focal areas of hypoperfusion in the posterior temporoparietal-occipital regions. At the earliest inversion time producing cortical enhancement, the ratios of parieto-occipital and temporo-occipital to whole slice signal intensity were significantly lower in the AD patients than in the controls. Parieto-occipital hypoperfusion correlated with dementia severity as measured by the Blessed Dementia Scale. EPISTAR may prove to be a rapid, noninvasive alternative to other functional neuroimaging modalities in the evaluation of patients with dementia.

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PubMed1995

Plasmapheresis in fulminant acute disseminated encephalomyelitis.

We describe two patients with fulminant acute disseminated encephalomyelitis (ADEM) treated with plasmapheresis after they failed to improve on steroids. Both patients improved concomitant with the plasma exchange. These are the first reported cases of fulminant ADEM with extensive white matter abnormalities on imaging studies treated with a regimen of plasmapheresis and steroids. Plasmapheresis may be beneficial in this disorder.

Adult↗
PubMed1992

Cerebral perfusion in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder in which structurally preserved cerebral cortex is thought to be functionally disconnected by subcortical lesions. To assess brain functional activity in patients with PSP, we measured regional cerebral perfusion, as estimated by [123I] iofetamine (IMP) and single-photon emission computed tomography (SPECT), in 11 patients with a clinical diagnosis of PSP and 10 healthy control subjects. IMP uptake was measured in 2 basal ganglia and 24 cortical regions. Neuropsychological tests were administered to assess cognitive function. Compared to age-matched normal control subjects, relative IMP uptake was significantly reduced in PSP patients in basal ganglia (21%), superior frontal (25%), anterior parietal (19%), and inferior frontal (18%) regions. Cognitive performance was most abnormal on tests thought to be subserved predominantly by frontal lobes. Our study demonstrates that IMP-SPECT detects physiological abnormalities in the cortex that parallel behavioral impairments in PSP.

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