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Biomedical subjects

S H Ferris

Publications and source records attributed to S H Ferris.

At least 19 recordsLinked to original sources

Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Pathophysiologic implications.

Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD.

Aged

Hypersensitivity to scopolamine in the elderly.

Scopolamine hydrobromide, 0.43 mg/70 kg, was administered by subcutaneous injection to ten young and ten elderly subjects. A comprehensive neuropsychological test battery was used to assess the effects of scopolamine, as compared to placebo, on cognitive function. As previously reported for this group of young subjects, scopolamine significantly impaired performance on tests of recent memory and visuospatial praxis. The same effects were observed in the elderly subjects, but the magnitude of the effects was much larger. The scopolamine injections produced significant psychomotor slowing in the elderly, whereas higher doses of the drug are required to produce this effect in young subjects. In both young and old subjects scopolamine failed to affect immediate memory, language function, object sorting, and the frequency of intrusion errors (although trends toward an effect were more apparent in the elderly). Remote memory, tested in the elderly only, was also unaffected. The results suggest that scopolamine's cognitive effects are quantitatively more pronounced in elderly subjects than young subjects, but that they are qualitatively similar and do not constitute a valid model for the cognitive dysfunction associated with Alzheimer's disease.

Adolescent

Pharmacologic treatment of Alzheimer's disease: a methodologic critique based upon current knowledge of symptomatology and relevance for drug trials.

Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the "cognitive domain" and the second the "noncognitive behavioral domain." Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD. The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed.

Activities of Daily Living

Mild cognitive impairment in the elderly: predictors of dementia.

We conducted full diagnostic evaluations, including a comprehensive cognitive assessment battery, of a group of 32 elderly subjects with a clinically identified mild cognitive impairment and a group of 32 age-matched and education-matched normal subjects. The mildly impaired subjects performed significantly more poorly than the controls on tests of recent memory, remote memory, language function, concept formation, and visuospatial praxis. Follow-up evaluations of cognitive status 2 years later revealed clinically detectable cognitive decline relative baseline in 23 (72%) of the mildly impaired subjects. Several of the objective psychological tests accurately discriminated at baseline between the decliners and nondecliners in the mildly impaired group. Among the 20 mildly impaired subjects with no complicating conditions, 16 exhibited cognitive deterioration between baseline and follow-up. These results suggest that most elderly subjects with mild cognitive deficits, as determined by clinical evaluation and objective psychological testing, will manifest the progressive mental deterioration characteristic of dementia and that psychometric predictors can be used to distinguish between benign and more significant underlying disorders in mildly impaired elderly subjects.

Aged

Scales for the assessment of Alzheimer's disease.

The clinical symptoms of Alzheimer's disease must be assessed and characterized comprehensively to confirm a diagnosis of dementia, to follow the course of the illness, and to evaluate the effects of treatment. Comprehensive assessment measures are multi-item scales that evaluate the various core cognitive symptoms of dementia and that provide a total score representing the overall magnitude of cognitive impairment. Neuropsychologic test batteries provide more detailed, objective evaluations of the various cognitive functions that are impaired. Global staging methods provide a single measure of the stage or severity of dementia, which is useful for tracking the clinical course and for comparisons among different studies. Scales to assess activities of daily living (basic physical functions and more complex instrumental activities) provide the most clinically relevant information regarding a patient's capacity to function in daily life. Finally, noncognitive behavioral symptom scales evaluate the secondary dementia symptoms (depression, agitation, hallucinations, delusions, etc.) that provide the greatest difficulty for patient management.

Alzheimer Disease

Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed.

Scopolamine hydrobromide was administered by subcutaneous injection to 30 young subjects in a dose of 0.22 mg/70 kg, 0.43 mg/70 kg, or 0.65 mg/70 kg. Treatment effects were compared to placebo on an extensive cognitive assessment battery. Almost all tests in the battery had been previously administered to Alzheimer's disease patients and nondemented elderly subjects. Scopolamine produced deficits on tests of verbal recall, visuospatial recall, visual recognition memory, visuospatial praxis, visuoperceptual function, and psychomotor speed. Immediate memory, language function, object sorting, and frequency of intrusion errors were unaffected. The low dose of scopolamine produced some peripheral anticholinergic signs but did not affect the cognitive measures. The results support the conclusion reached in previous studies that the cognitive profile of scopolamine-injected young subjects is more similar to that of the nondemented elderly than to that of Alzheimer's disease patients.

Adolescent

Impaired facial recognition memory in aging and dementia.

Young normals, aged normals, and patients with early and advanced probable dementia of the Alzheimer type (DAT) were administered a facial recognition memory task. A continuous recognition paradigm was used, in which subjects were instructed to identify the repeated faces in an ongoing series of faces presented on a video monitor screen. A signal detection analysis of the data revealed that the DAT patients were markedly impaired in their ability to discriminate between new and repeated faces. Multiple presentations of faces improved the recognition accuracy of the early DAT patients only, but their rate of learning was slower than that of the normal subjects. In comparison to the young normals, elderly normals exhibited a mild deficit in recognition memory. All of the elderly subject groups exhibited a more liberal response bias than the young normals, which eliminates the possibility that the impaired memory task performance of the aged subjects could be attributed to a more conservative test-taking strategy. The DAT patients exhibited impaired recognition even when the second presentation of a face immediately followed the first, which perhaps implies that task performance was also sensitive to the effect of DAT on visuoperceptual abilities or psychomotor speed.

Adolescent

The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.

Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.

Affect

Alzheimer's disease: longitudinal CT studies of ventricular change.

A 3-year longitudinal study was conducted with 50 Alzheimer's disease patients and 45 elderly control subjects. All study participants received an extensive evaluation that included brain CT at baseline and follow-up. Quantitation of ventricular size, using both linear and volume methods, revealed highly significant cross-sectional and longitudinal differences between the Alzheimer patients and control subjects. Specifically, the annual rate of change in ventricular volume was approximately 9% in the Alzheimer patients and approximately 2% in the controls. The presence of age-related white matter lesions had no effect on the clinical course of the patients or on the changes in ventricular size. Among the Alzheimer patients, the rate of clinical decline was strongly related to the rate of change in ventricular size. Baseline ventricular measurements were of no value in predicting the subsequent rate of clinical deterioration or ventricular enlargement. The results suggest that changes in ventricular size closely reflect the clinical changes in Alzheimer patients.

Aged

The stage specific temporal course of Alzheimer's disease: functional and behavioral concomitants based upon cross-sectional and longitudinal observation.

A series of studies published over the past 6 years now permit a relatively precise description of the temporal course of Alzheimer's disease (AD). Initially, 7 global stages of CNS aging and AD were described. Subsequently, data on the stage specific relationship between these stages and widely employed mental status, psychometric, and other assessment measures were collected. Longitudinal studies helped to clarify the borders between normal CNS aging and AD using these measures. Other studies described functioning and self-care correlates of the 7 global stages. These were ultimately divisible into 16 clearly defined, ordinal functional stages. Empirical longitudinal observations permitted the description of the mean temporal course of each of the 16 functional stages of aging and AD. The cross-sectional stage specific data on mental status and other measures can now be applied to the mean temporal course observations and the validity of the temporal estimates forwarded can be investigated in detail. Etiologic hypotheses based upon the observed phenomenologic and temporal course of AD are discussed.

Aging

Clinical features of a neuropathologically verified familial Alzheimer's cohort with onset in the fourth decade: comparison with senile onset Alzheimer's disease and etiopathogenic implications.

Clinical and pathologic features of a family with early onset, autosomal dominant, familial Alzheimer's disease (AD) are compared and contrasted with senile onset dementia of the Alzheimer type. Late onset AD has previously been observed to have a characteristic progression and clinical course. A previously unreported pedigree, with two siblings and their father affected, of early clinical onset is presented. Molecular genetic study of this family using in situ chromosome hybridization showed an apparent marker on chromosome 9. This early onset form of AD is observed to be clinically consistent with the common late onset form of AD, but follows a more rapid course. An etiopathogenic model explaining the early onset, and other forms of AD is presented.

Adult

Equivalent spatial-rotation deficits in normal aging and Alzheimer's disease.

Two tests of spatial-rotation ability were administered to 17 young normals, 23 aged normals, and 51 patients with diagnoses of Alzheimer's disease (AD). The AD patients consisted of 28 early dementia patients and 23 advanced dementia patients. On a computerized version of the Boston Naming Test, 40 objects were presented for naming, 20 of which were rotated 180 degrees. The subjects' capacity for mental rotation was assessed on the basis of their accuracy of naming of rotated vs. unrotated objects. On Money's Standardized Road Map Test, in which the subject is asked whether turns on a map are to the left or to the right, spatial-rotation ability was assessed on the basis of the subject's left-right orientation on turns with movement away from the subject (requiring no rotation) vs. turns with movement toward the subject (requiring rotation). Performance on both tasks was progressively worse in the young normal, aged normal, early dementia, and advanced dementia groups. Both tasks demonstrated a clear spatial-rotation deficit in the elderly. Although the spatial-rotation effect was superimposed upon deficits in naming and left-right orientation in the demented subjects, the magnitude of the rotation effect did not significantly differ in the aged normal vs. the early dementia group on either task, suggesting that early AD produces no further impairment of spatial-rotation abilities than is produced by normal aging.

Adolescent