David Masur

Clinico‐pathologic studies in dementia: Nondemented subjects with pathologically confirmed Alzheimer's disease

We compared neuropsychological findings in 28 longitudinally evaluated elderly subjects with their postmortem neuropathology, including senile plaque and neurofibrillary tangle counts from standardized sections. Nine of the subjects were not demented when evaluated just prior to their death. Numerous cortical senile plaques and other changes of Alzheimers disease (AD) occurred in six of nine nondemented old-old subjects. Five of these six subjects had shown decline on yearly neuropsychological tests but their cognitive impairment was too mild to meet clinical criteria for dementia. Whereas cortical senile plaque count did not distinguish well between demented and nondemented subjects, every subject with numerous cortical neurofibrillary tangles was demented. The nondemented subjects with Alzheimer pathology may have had “preclinical” AD, or numerous cortical plaques may occur in some elderly subjects who would never develop clinical dementia.

Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons

Identification of elderly individuals with low and high risk for future dementia has emerged as an important clinical and public health issue. To address this issue, we assessed neuropsychological performance in 317 initially nondemented elderly persons between 75 and 85 years of age and followed them for at least 4 years as part of the Bronx Aging Study. Four measures of cognitive function from the baseline assessment (delayed recall from the Buschke Selective Reminding Test, recall from the Fuld Object Memory Evaluation, the Digit Symbol subtest from the Wechsler Adult Intelligence Scale, and a verbal fluency score) can identify one subgroup with an 85% probability of developing dementia over 4 years and another with a 95% probability of remaining free of dementia. The model achieved an overall positive predictive value of 68%, or three times the base rate, for prediction of the development of dementia in our sample. The overall negative predictive value for prediction of absence of dementia was 88%. Baseline measures of cognitive function, often performed many years before the actual diagnosis of dementia, can provide important information about dementia risk. The group likely to develop dementia becomes a target for preventive or early therapeutic interventions, and the group unlikely to develop dementia can be reassured.

Psychiatric Disorders in Patients With Fibromyalgia: A Multicenter Investigation

The authors conducted an investigation in four tertiary-care centers to determine if psychiatric comorbidity and psychological variables were predictive of functional impairment in patients with fibromyalgia syndrome (FMS). Seventy-three individuals were administered the Structured Clinical Interview for DSM-III-R, the Rand 36-item Health Survey (SF-36), and multiple self-report measures. The patients with FMS were found to have a high lifetime and current prevalence of major depression and panic disorder. The most common disorders were major depression (lifetime [L] = 68%, current [C] = 22%); dysthymia (10% [C only]); panic disorder (L = 16%, C = 7%); and simple phobia (L = 16%, C = 12%). The self-report scales revealed significant elevations in depression, anxiety, neuroticism, and hypochondriasis. Functional impairment on all measures of the SF-36 was severe (e.g., physical functioning = 45.5 and role limitations due to physical problems = 20.0). Stepwise multiple-regression analysis revealed that current anxiety was the only variable that predicted a significant proportion of the variance (29%) in SF-36 physical functioning. Thus, in this multicenter study, the persons with FMS exhibited marked functional impairment, high levels of some lifetime and current psychiatric disorders, and significant current psychological distress. Current anxiety level appears to be an important correlate of functional impairment in individuals with FMS.

Women, myocardial infarction, and dementia in the very old

Dementia is a major public health problem among the very old. Available information on incidence and prevalence is sparse and variable; however, there appears to be a higher prevalence among very old women. We present data from a prospective study of initially nondemented community-residing elderly. There were 75 incident dementia cases (up to 7 years of follow-up) of which at least 47% were probable Alzheimers disease. Based on a proportional hazards analysis, women were over 3 times more likely to develop dementia than men despite controlling for baseline demographic, psychosocial, and medical history variables. Poor word fluency and a high normal Blessed test score at baseline were also strong predictors of dementia. We did not find age, head trauma, thyroid disease, or family history of dementia to be risk factors. A new finding is that history of myocardial infarction (MI) is associated with dementia, such that women with a history of MI were 5 times more prone to dementia than those without a history. This observation was not true for men.

Object-memory evaluation for prospective detection of dementia in normal functioning elderly : predictive and normative data

In a prospective study of dementia in initially normal functioning elderly, a brief form of the Fuld Object-Memory Evaluation (OM) was administered to 474 cognitively normal community-residing volunteers aged 75-85 at baseline and annually thereafter. Seventy-two subjects later became demented. Memory test data from the last annual evaluation before cognitive change was noted were available for 56. Although the entire population recalled 7.28 (SD = 1.33) of the 10 objects on Trial 1 of the test at baseline, these 56 subjects recalled only 5.96 (SD = 1.85). When recall of 6 or fewer objects was used as a predictor, the OM test identified 32 of the 56 who subsequently became demented. Compared to an estimated base rate of 15% for dementia, the predictive value of a positive test (PV+) was 39%, and that of a negative test (PV-) was 89%. With a cutoff of 5 or fewer items recalled, the PV+ rose to 59% and the PV- was 94%. Although the OM test was only moderately sensitive to incipient dementia (.57), it was fairly specific (.84), and lowering the cutoff to 5 increased the specificity to .96. Memory testing would therefore seem to hold promise as a predictor of dementia in cognitively normal elderly.

Ethosuximide, Valproic Acid and Lamotrigine in Childhood Absence Epilepsy: Initial Monotherapy Outcomes at 12 months

Purpose:  Determine the optimal initial monotherapy for children with newly diagnosed childhood absence epilepsy (CAE) based on 12 months of double‐blind therapy.

Worsening of quality of life after epilepsy surgery Effect of seizures and memory decline

Background: Surgery for intractable temporal lobe epilepsy usually controls seizures and improves health-related quality of life (HRQOL), but some patients experience continued seizures, memory decline, or both. The relative impact of these unfavorable outcomes on HRQOL has not been described. Methods: We studied seizure control, memory change, and HRQOL among 138 patients in the Multicenter Study of Epilepsy Surgery (MSES), an ongoing, prospective study of epilepsy surgery outcomes. Seizure remission at 2 years and 5 years was prospectively determined based upon regularly scheduled follow-up calls to study patients throughout the follow-up period. HRQOL was assessed annually using the Quality of Life in Epilepsy Inventory (QOLIE-89). Memory decline was determined by change in verbal delayed recall from baseline to the 2- or 5-year follow-up. Results: HRQOL improved in patients who were in remission at the 2-year or 5-year follow-up, regardless of memory outcome. Among those not in remission at both 2 and 5 years (25/138, 18%), HRQOL remained stable when memory did not decline (14/138, 10%), but HRQOL declined when memory did decline (11/138, 8%). These 11 patients had baseline characteristics predictive of poor seizure or memory outcome. Declines were most apparent on HRQOL subscales assessing memory, role limitations, and limitations in work, driving, and social activities. Conclusions: After temporal resection, health-related quality of life (HRQOL) improves or remains stable in seizure-free patients despite memory decline, but HRQOL declines when persistent seizures are accompanied by memory decline. These results may be useful in presurgical counseling and identifying patients at risk for poor psychosocial outcome following surgery.

Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study

Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute hippocampal injury that evolves to HS.

Distinguishing normal and demented elderly with the selective reminding test.

The selective reminding (SR) procedure, a popular technique for the study of verbal memory, was used to investigate aspects of memory functioning in a large group of normal elderly and in a smaller group of elderly subjects with Alzheimer Type Dementia (ATD). One hundred thirty-four normal elderly (mean age = 79.53 years) subjects and 21 ATD subjects (mean age = 68.3 years) were administered four versions of the SR test as part of a longitudinal study of risk factors in the development of dementia. Normative data were obtained for multiple components of memory functioning within the elderly sample. Test-retest reliability was .84 for long-term retrieval (LTR), .89 for sum of recall, and .92 for consistent retrieval. Clinical validity studies revealed that the components of sum of recall, storage estimate, LTR, and consistent long-term storage (CLTS) were most valuable in distinguishing mild ATD from normal aging. Positive predictive values ranged from 86% for CLTS, 89% for LTR, 91% for sum of recall, and 100% for storage estimate. These findings suggest that the SR test has considerable clinical utility in differentiating normal aging from dementia, and has promise as a useful tool in the preclinical detection of ATA.

Predicting development of dementia in the elderly with the Selective Reminding Test

The ability to predict the development of dementia through the detection of memory impairment in nondemented individuals was assessed with the Selective Reminding Test (SR), a popular test of verbal memory functioning in the elderly. The SR was administered to 385 nondemented volunteer subjects (mean age = 80.4 years) enrolled in a longitudinal study of risk factors in the development of dementia. Of these, 36 subjects ultimately became demented. SR scores obtained from 1 to 2 years prior to the diagnosis of dementia were compared with a set of previously established cutoff scores derived from a cognitively normal elderly sample. The results demonstrated that sum of recall and delayed recall were the SR measures best able to predict dementia with sensitivities of 47% and 44%, respectively. The predictive values were 37% and 40%, respectively, or better than two-and-one-half times the base rate. The contributions of both the SR Test and the Fuld Object-Memory Test (OM) were discussed in terms of the further understanding of the characteristics of the preclinical phase of dementia.