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A Kluger

Publications and source records attributed to A Kluger.

36 records · Page 2Linked 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↗

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↗

Cognition-independent neurologic symptoms in normal aging and probable Alzheimer's disease.

Deep tendon reflexes, plantar responses, muscle tone, and release signs were studied as 14 individual clinical variables and as five summary variables in 135 aged subjects, including 27 control subjects, 20 subjects with mild cognitive impairment, and 88 subjects with successive stages of probable Alzheimer's disease. Changes in activity of elicited responses were rated on a seven-point scale. Results were analyzed both as prevalence and mean degree of change in activity. Rating on a variable combining all 14 individual variables was significantly higher in a group with mild cognitive impairment than in a control group. Subjects with an early stage of Alzheimer's disease had both higher prevalence of increased activity and increased mean scores of deep tendon reflexes and muscle tone. They had a higher prevalence of increased activity on a variable combining three release signs. Patients with a late stage of Alzheimer's disease had significantly increased prevalence and mean scores of muscle tone and grasping and sucking reflexes compared with control subjects and patients with the early stage of Alzheimer's disease.

Activities of Daily Living↗

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↗

IQ patterns in affective disorder, lateralized and diffuse brain damage.

Meta-analysis of 38 studies compared Wechsler IQ scores in affective disorder (A), lateralized right (RH), left (LH) and bilateral/diffuse (BI) brain damage. A, RH, and BI had lower PIQ than VIQ. In A and BI groups the PIQ/VIQ ratio was identical, whereas each differed significantly from the RH group which revealed a much lower PIQ/VIQ ratio. Similarity of neuropsychological profiles of A and RH patients is often interpreted as indicating predominant right-hemisphere involvement in affective disorder. The present findings suggest an alternative interpretation is possible: i.e., the presence of bilateral/diffuse CNS involvement in affective disorder. We do not believe that our findings strongly support one interpretation over the other. In future research, both possibilities should be considered.

Adult↗

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↗

Abnormal temporal lobe response in Alzheimer's disease during cognitive processing as measured by 11C-2-deoxy-D-glucose and PET.

Elderly controls and probable Alzheimer's disease patients underwent serial positron emission tomography (PET) studies during a baseline condition and while performing a verbal memory task. For the temporal lobes, all 7 Alzheimer patients demonstrated a relative shift in glucose metabolic rates to the right hemisphere during the memory condition relative to baseline, and 5 of 7 controls showed a shift to the left hemisphere. Baseline absolute regional metabolic rates replicate previous findings and were somewhat less useful than the memory challenge in differentiating patients from controls. These results indicate that a temporal lobe abnormality in Alzheimer's disease is related to memory performance.

Aged↗

Positron emission tomography studies of normal aging: a replication of PET III and 18-FDG using PET VI and 11-CDG.

Using PET VI and 11-CDG we replicated our earlier PET III and 18-FDG normal aging findings. Examination of young and old normal volunteers revealed the absence of any absolute regional age-related changes in glucose utilization. For the combined sample (N = 81) we did find evidence to suggest a relative hypofrontal change with increasing age. A strong relationship between age and ventricular size (CT) was also found. These findings suggest the preserved glucose metabolism of the resting aging brain in the presence of structural atrophic changes.

Adult↗

Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease.

We used CT and MR to examine the frequency of occurrence of hippocampal formation atrophy (HA) in a research clinic population of 130 normal elderly, 72 nondemented patients with very mild memory and cognitive impairments (MCI), 73 mild Alzheimer's disease (AD) patients, and 130 patients with moderate to severe AD. HA was found in 29% of the normal elderly group and its frequency of occurrence was strongly related to increasing age. For normal elderly 60-75 years of age, 15% had HA: the proportion rose to 48% in subjects 76-90 years of age. Among the three groups of impaired patients, the frequencies of HA ranged from 78% in the MCI patients to 96% in the advanced AD group. Unlike the normal elderly group, the percentages were not related to age. In both the normal elderly group and MCI group disproportionately more males than females had HA. After controlling for learning and the effects of generalized brain changes as reflected in ventricular size, only in the normal group was HA associated with reduced delayed verbal recall performance. Follow-up examinations for 15 individuals with baseline HA. 4 who at entry were MCI and 11 probable AD, yielded clinical and neuropathologic diagnoses of AD in all cases. The results of the present study indicate that hippocampal formation atrophy is associated with memory and cognitive impairments. Further longitudinal and neuropathologic work is required to validate the relationship between hippocampal formation atrophy and AD.

Aged↗

Hippocampal formation size in normal human aging: a correlate of delayed secondary memory performance.

Although mild progressive memory impairment is commonly associated with normal human aging, it is unclear whether this phenomenon can be explained by specific structural brain changes. In a research sample of 54 medically healthy and cognitively normal elderly persons (ages 55-87, x = 69.0 +/- 7.9), magnetic resonance imaging (MRI) was used to derive head-size-adjusted measurements of the hippocampal formation (HF) (dentate gyrus, hippocampus proper, alveus, fimbria, subiculum), the superior temporal gyrus (STG), and the subarachnoid cerebrospinal fluid (CSF) (to estimate generalized cerebral atrophy). Subjects were administered tests of primary memory (digit span) and tests of secondary memory with immediate and delayed recall components (paragraph, paired associate, list recall; facial recognition). Separate composite scores for the immediate and delayed components were created by combining, with equal weighting, the subtests of each category. The WAIS vocabulary subtest was used as a control measure for language and intelligence. A highly significant correlation (P < 0.001), independent of age, gender, and generalized cerebral atrophy was found between HF size and delayed memory performance. No significant correlations were found between HF size and primary or immediate memory performance. STG size was not significantly correlated with any of the composite memory variables. These results suggest that HF atrophy may play an important independent role in contributing to the memory loss experienced by many aging adults.

Aged↗

CT diagnostic features of Alzheimer disease: importance of the choroidal/hippocampal fissure complex.

Neuropathologic changes in the temporal lobe, including focal atrophy of the subiculum and entorhinal cortex, have been described in association with Alzheimer disease. We studied the usefulness of detecting temporal-lobe structural changes on CT in making the diagnosis of Alzheimer disease. The dementia imaging protocol we use includes thin-section (5 mm) cuts of the temporal lobe oriented 20 degrees negative (caudal) to the plane of the canthomeatal line. Thirty-four patients with suspected Alzheimer disease and 20 normal elderly control subjects, all between 65 and 80 years old, were studied with a standard protocol that also included neurologic and medical examinations and detailed psychometric testing. All the temporal-lobe evaluations of the five variables measured were significantly associated with the presence or absence of Alzheimer disease. Almost all Alzheimer patients showed evidence of mild or greater severity of overall temporal-lobe atrophy. The absence of temporal-lobe atrophy, seen in approximately one half the normal cases, identified normal individuals with a high degree of specificity (95%). The presence of characteristic hippocampal lucency, apparently due to enlargement of the choroid and hippocampal fissures, showed the highest sensitivity and classification accuracy of all the variables tested (82 and 80% respectively; p less than .001), correctly identifying 82% of Alzheimer patients and 80% of Alzheimer patients and control subjects. These results indicate that CT detection of structural changes in the temporal lobe and hippocampus strongly support the diagnosis of Alzheimer disease. A temporal-lobe imaging protocol for CT, and by extension for MR, is suggested for the evaluation of patients with the clinical diagnosis of a dementing disorder.

Aged↗