We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development.

Aged↗

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Elevated cortisol levels in Cushing's disease are associated with cognitive decrements.

OBJECTIVE: The objective of this study was to use Cushing's disease as a unique human model to elucidate the cognitive deficits resulting from exposure to chronic stress-level elevations of endogenous cortisol. METHODS: Forty-eight patients with a first episode of acute, untreated Cushing's disease and 38 healthy control subjects were studied. RESULTS: Scores for four of five verbal IQ subtests were significantly lower in patients with Cushing's disease; their scores were significantly lower for only one nonverbal performance IQ subtest (block design). Verbal, but not visual, learning and delayed recall at 30 minutes were significantly decreased among patients with Cushing's disease. Although verbal delayed recall was significantly lower in these patients, the retention index (percentage), which compares the amount of initially learned material to that recalled after the delay, was not significantly decreased. There was no significant association between depression scores and cognitive performance. A higher degree of cortisol elevation was associated with poorer performance on several subtests of learning, delayed recall, and visual-spatial ability. CONCLUSIONS: Chronically elevated levels of glucocorticoids have deleterious effects on particular domains of cognition. Verbal learning and other verbal functions seem more vulnerable than nonverbal functions. The results suggest that both the neocortex and hippocampus are affected.

Adult↗

PubMedDate not supplied

Intelligence test performance of patients with partial and generalized seizures.

The intellectual performance of 350 patients with seizures was examined. Seizures were classified according to the revised International Classification of Epileptic Seizures as partial (simple or complex), generalized, or partial secondarily generalized. Performance on the Wechsler Intelligence subtests served to measure intellectual ability. Patients with partial seizures performed better on Digit Span, Digit Symbol, Block Design, and Object Assembly than those with either generalized or partial secondarily generalized seizures. These subtests are functionally associated with abilities such as attention, visuospatial problem-solving, and sequencing ability.

Adolescent↗

PubMedDate not supplied

Pilot study of zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in patients with refractory partial seizures.

A new anticonvulsant compound, zonisamide (1,2 benzisoxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were higher than plasma concentrations because of red blood cell binding. Steady-state plasma concentrations were higher than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal systems were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day.

Adult↗

PubMedDate not supplied

Academic achievement of children with epilepsy.

The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables. As a group, these children were making less academic progress than expected for their age and IQ level. Academic deficiencies were greatest in arithmetic, followed by spelling, reading, comprehension, and word recognition. Results of the multiple regression analyses indicated a modest combined predictive significance of the demographic and clinical seizure variables for academic performance. In addition, the magnitude of these relationships varied by academic area. Among the individual variables examined the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures (absence and tonic-clonic). These results are discussed in relation to developing an understanding of the factors which underlie academic vulnerability in children with epilepsy.

Achievement↗

PubMedDate not supplied

Zonisamide (CI-912) and cognition: results from preliminary study.

Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (1,2-benzisoxazole-3-methanesulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations greater than 30 micrograms/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p less than 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects.

Adult↗

PubMedDate not supplied

Serial cognitive testing in temporal lobe epilepsy: longitudinal changes with medical and surgical therapies.

Cognitive testing was repeated at intervals ranging from 1 to 8 years in 47 adult patients with temporal lobe epilepsy (TLE). Each patient underwent standardized batteries, including the Wechsler Adult Intelligence Scale, Revised (WAIS-R), and Wechsler Memory Scale (WMS). Both surgically treated and nonsurgical patients were examined. The nonsurgical group underwent serial testing for clinical indications, usually for complaints of memory dysfunction. Longitudinal testing could not verify any mean deterioration of intellect or memory in this group; variance over time was similar to test-retest norms in healthy controls. WAIS-R scores before and after resection in the surgical group were similar to our serial WAIS-R data in nonsurgical patients. When we divided surgical patients according to side of epileptogenesis, we noted the expected differences in verbal and visual memory. Right-sided surgery patients improved significantly in Full-Scale IQ (FSIQ) and tended to improve in logical memory on postoperative testing. Patients undergoing left resections had no retest improvement and tended to show decrease in several measures of verbal memory. Our findings should stimulate continued investigation into the natural history of lateralized memory and intellectual function in epilepsy, particularly to clarify long-term cognitive outcome in nonsurgical patients.

Adult↗