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To assess the the effect of antiplatelet therapy on the severity of subsequent stroke in patients with stroke and TIA.

To determine whether there is a causal link between vigabatrin treatment and concentric visual field defects and to evaluate the prevalence of these visual field constrictions.

We treated 75 patients with drug-resistant complex partial seizures and secondarily generalized seizures with vigabatrin as additional therapy for 6 months. Twenty-one patients either showed no benefit from vigabatrin treatment or had side effects. The remaining 54 patients entered into the long-term study. The median monthly seizure frequency decreased from 12.5 at baseline to 3.3 at the 3-month visit, and was 3.9 after 5 years of therapy in 28 patients who continued using the drug after the 5-year period. During 5 years of therapy with vigabatrin, 26 patients have withdrawn from the study because of various reasons: loss of efficacy (14), suspected side effects (5), noncompliance (3), administrative reasons (2), pregnancy (1), and epilepsy surgery (1). In all, 19 patients had a greater than 50 seizure frequency reduction at 5 years, representing 35 of the 54 patients who entered the long-term study, or 25 of the 75 patients who were initially recruited into the efficacy study.

To determine if the pattern of cognitive decline in Alzheimer's disease (AD) patients with normal EEG differs from that in patients with abnormal EEG at the early stage of the disease, we have followed 12 AD patients with normal EEG (NEEG) and 12 patients with deteriorating EEG (DEEG). The AD patients with DEEG showed a decline of praxic functions, confrontation naming, and automatic speech functions. In contrast, the AD patients with NEEG did not show a deterioration of these functions during the 3-year follow-up period. Visual functions, understanding of speech, and memory functions deteriorated similarly in both groups. The clinical severity of dementia increased in both groups. Patients with DEEG showed a tendency toward a higher frequency of extrapyramidal symptoms and a higher risk of institutionalization than the patients with NEEG. Thus, an abnormal EEG at the early stage of AD may predict a more severe decline in cognitive functions.

To investigate whether recurrent seizures cause hippocampal damage in temporal lobe epilepsy (TLE).

Article abstract-Aging has multiple effects on memory in normal subjects. However, information on the prevalence of age-associated memory impairment (AAMI) is scanty. We studied the prevalence of AAMI in a randomly selected population of 1,049 subjects aged 60 to 78 years from eastern Finland. Research criteria proposed by the National Institute of Mental Health (NIMH) Work Group were applied. We calculated prevalence rates for AAMI by the inclusion criteria alone (subjective and objective memory impairment and no dementia) as well as by the inclusion and exclusion criteria (evidence of any neurologic or other medical disorder that could produce cognitive deterioration) for the total study population, for both sexes, and for four age groups (60 to 64, 65 to 69, 70 to 74, and 75 to 78 years). Subjective memory impairment was present in 76.3% of the subjects. Prevalence rates for objective memory impairment ranged from 31.9 to 78.4% in individual tests. A total of 564 subjects (239 men, 325 women) were classified as having AAMI by the inclusion criteria alone, giving a prevalence rate of 53.8% (men, 57.4%; women, 51.3%). When we included the exclusion criteria, the prevalence of AAMI decreased to 38.4% (men, 42.5%; women, 35.7%). By both methods, age- and sex-specific prevalence rates were highest in the youngest group, aged 60 to 64 years, and lowest in the oldest group, aged 75 to 78 years. We conclude that the prevalence of AAMI, by the diagnostic criteria of the NIMH Work Group, is high in the elderly Finnish population. AAMI seems likely to be a phenomenon of normal aging rather than a continuum from normal aging to a pathologic state such as Alzheimer's disease.

Age-associated memory impairment (AAMI) is a common but disputed entity. It is unclear whether AAMI is a phenomenon of normal aging or an early sign of Alzheimer's disease. The present study aimed to identify possible structural abnormalities in the medial temporal lobe of AAMI subjects. We measured volumes of the hippocampus and amygdala by MRI in 16 AAMI subjects and in 16 age- and sex-matched controls and correlated the volumes with subjects' performance on two visual memory tasks (the Benton and the Heaton visual retention tests) and on a verbal memory task (the Buschke-Fuld Selective Reminding Test). The mean hippocampal and amygdaloid volumes normalized for brain size per se did not differ between the two study groups. In controls, but not in AAMI subjects, the right hippocampus was larger than the left. Accordingly, the volumetric asymmetry between the right and left hippocampi was smaller in AAMI subjects than in controls (Student's ttest, p<0.05). The volume of the right hippocampus (r = 0.37, n = 32, p<0.05) and the magnitude of the asymmetry between the right and left hippocampi (r = 0.38, n = 32, p<0.05) correlated with total score on the Benton test. We also found significant correlations between the amygdaloid volumes and the performance on visual memory tests but not with score on the verbal memory test. Furthermore, a subgroup of seven AAMI subjects with the lowest visual memory scores (≤5 on the Benton test) had smaller right and left amygdala (13, p<0.05) than the six controls with the highest scores (=9 on the Benton test). Thus, we demonstrate that minor structural changes are present in both the hippocampus and the amygdala in AAMI subjects compared with age-matched controls. Follow-up of the subjects will be necessary to determine whether these minor structural abnormalities predict development of dementia or just reflect increased variability of cognitive performance in elderly humans.

To assess frontal lobe functions of subjects with age-associated memory impairment (AAMI) and to examine whether performance on neuropsychological tests is correlated with the volume of the frontal lobes in magnetic resonance imaging. Design: Cross-sectional two-group comparison. Setting: The Memory Research Clinic of Kuopio University and the Magnetic Resonance Imaging Center of Kuopio University Hospital. Participants: Ninety subjects (mean age, 70.5 years), 43 with AAMI diagnosed according to National Institute of Mental Health criteria and 47 age-matched healthy controls. Measurements: Four neuropsychological tests were used to assess frontal lobe function: Verbal Fluency Test (VFT), Modified Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test (ST). A 1.5-T magnetic resonance imager was used for volume measurements. Results: The AAMI subjects scored significantly worse on the WCST, ST, and TMT compared with controls (ANCOVA, adjusted for age and education, p < 0.05). The frontal lobe volumes did not differ between AAMI subjects and controls. Conclusions: AAMI subjects appear to be impaired not only in tests assessing memory but also in tests of executive functions. This finding agrees with previous reports suggesting a central role for frontal dysfunction in memory loss of elderly people.

The synthetic ACTH 4–9 analog, Org 2766, was administered to 77 Alzheimer's patients for 6 months in a double-blind, placebo-controlled study. Although Org 2766 was tolerated well, no significant effect of Org 2766 could be demonstrated in terms of rating scales or cognitive functions.

The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid tid with placebo in the prevention of stroke or death after one or more attacks of recent transient ischemic attack or stroke of atherothrombotic origin. From the 2,500 patients in the intention-to-treat analysis, the proportion of women was 42, and from the 1,861 patients in the explanatory analysis it was 44. The endpoint incidence was significantly higher in men than in women. The endpoint reduction was statistically significant in men in both types of analyses with total endpoints (stroke or death) and in the risk of stroke, while in women it was statistically significant only in the intention-to-treat analysis with total endpoints. However, there was a marked percentage reduction of endpoints in both men and women in explanatory analysis. The risk reduction of strokes was 49 for men and 41 for women, and the reduction of total endpoints was 39 in men and 30 in women. Thus, antiplatelet therapy is effective in the prevention of stroke or death in both sexes.

We studied the antiepileptic potency of vigabatrin (γ-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43) of the patients with seizures of partial onset and 2 (33) with PG had more than 50 reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.

We quantified microtubule-associated protein tau in CSF (CSF tau) using ELISA assay in 168 subjects: 81 patients with clinically diagnosed early Alzheimer's disease (AD), 43 patients with other dementia, 11 Down's syndrome patients, and 33 nondemented neurologic control subjects. Multivariate ANOVA showed an effect on diagnostic group (p< 0.01) and apolipoprotein E (apoE) allele (p< 0.005) on CSF tau. Comparison between diagnostic groups showed higher CSF tau levels in AD than in the control group (p< 0.001). However, CSF tau values in the non-AD dementia group did not differ significantly from those of AD patients or neurologic control subjects. Tau levels were increased(p< 0.005) in AD patients with apolipoprotein E 4 allele, a well-characterized risk factor of AD, compared with AD patients without 4 allele, and the highest values were found in AD patients with two 4 alleles. These increased levels of CSF tau may indicate pronounced neuronal degeneration and neurofibrillar pathology at the early stage of AD in patients carrying the 4 allele. This study shows that the current ELISA test for CSF tau is not sensitive and specific enough to distinguish early AD from other dementias and indicates that in the interpretation of CSF tau analysis as a diagnostic tool, the apoE genotype should also be taken into account.

We carried out a double-blind study of a vasopressin-related peptide, DGAVP citrate (Org 5667), in 115 patients with mild dementia, probable Alzheimer's type (DAT). Neither clinical rating scales nor psychometric tests revealed any improvement over 84 days with once-daily intranasal treatment with 2 different doses of DGAVP. We conclude that vasopressin-like peptides are not satisfactory therapeutic agents in DAT.

Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease.In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon 4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (more than equals to 65 years), familial late-onset (FLO) (more than equals to 65 years), sporadic early-onset (SEO) (less than 65 years), and familial early-onset (FEO) (less than 65 years) patients and into three subgroups according to their ApoE genotype zero epsilon 4, one epsilon 4, and two epsilon 4 alleles. The AD subgroups did not differ in the global clinical severity of dementia or the duration of the disease. SLO, FLO, SEO, and FEO subgroups did not differ in clinical characteristics such as occurrence of rigidity, hypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions. The epsilon 4 allele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of onset. Patients with two epsilon 4 alleles had earlier age at onset of dementia than those with no epsilon 4 allele (63 plus minus 9 versus 68 plus minus 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 alleles had lowest scores on memory tests and differed significantly from those with one or zero epsilon 4 allele in the delayed list learning (p less than 0.05) and from those with zero epsilon 4 allele in the immediate and delayed story recall. In contrast, verbal functions were better preserved in two epsilon 4 patients than in those with other ApoE genotypes. This study failed to confirm the earlier reports of severe aphasia, agnosia, and apraxia in familial AD patients, but the clinical phenotype was similar irrespective to the familial aggregation. However, AD patients with two epsilon 4 alleles are characterized by more severe memory loss and earlier age of onset than those without the epsilon 4 allele.

We analyzed hippocampal volumes and T sub 2 relaxation times by MRI from 78 control subjects, 24 patients with temporal lobe epilepsy, and 55 patients with Alzheimer's disease (AD).In the epilepsy group, the hippocampal volumes were 27% smaller than in control subjects (p < 0.001). The T2relaxation times were prolonged (8 to 20 ms compared with control subjects) in the head, body, and tail portions of the hippocampus on the focal side (p < 0.01) and also on the contralateral side (p < 0.05) compared with control subjects. In the epilepsy group, the prolongation of T2relaxation time correlated inversely with the hippocampal volume (p < 0.05). In the AD group, the hippocampal volumes were 35% smaller than in control subjects (p < 0.01). The T2relaxation times were slightly prolonged (5 to 6 ms) in the head and tail portions of the right hippocampus (p < 0.01), but the T2relaxation times did not correlate with the hippocampal volumes. These data show that the degree of prolongation of T2relaxation time is associated with severity of hippocampal atrophy in temporal lobe epilepsy but not in AD.