Paula A. Fuld

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.

Impaired ranking of semantic attributes in dementia

The present work explored the loss of semantic attributes that is said to occur in dementia. In the first two experiments, subjects had to select attributes that went with concepts like airplane and church. The finding that demented subjects maintained high levels of accuracy when selecting attributes suggested that the semantic content of their concepts was relatively well preserved. The organization of the content was explored in a third experiment by having subjects order attributes according to their relative importance in defining concepts. While demented subjects performed better than chance, they did not rank attributes as well as healthy aged subjects, suggesting a disruption in organization whereby the importance of central attributes is reduced. The hypothesized disruption in organization is viewed in relation to the learning and memory deficit that is the hallmark of the dementias.

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.

Test profile of cholinergic dysfunction and of Alzheimer-Type dementia

A characteristic profile of subtest scores from the Wechsler Adult Intelligence Scale (WAIS) similar to that seen in clinically tested dementia patients was found in 10 of 19 normal young adult subjects with a drug-induced cholinergic deficiency of mental functioning but in only 4 of 22 control subjects. The same subtest profile was then found in test data from two groups of consecutive dementia patients (61 and 77 patients, respectively) with research diagnoses of Alzheimer-type dementia (DAT, senile and presenile), multi-infarct, and other dementias. The profile identified 44% of testable patients with AD and was 96% specific to DAT (only two false positives). A Verbal-Performance IQ discrepancy of 15 or more points was associated with cholinergic dysfunction in the normal drug subjects, but this IQ-score discrepancy did not differentiate AD from multi-infarct dementia patients. It was concluded that the subtest profile could contribute to the differentiation of DAT from other dementias. The association of this profile with drug-induced cholinergic deficiency suggested that the cholinergic deficiency of DAT might be responsible for the intellectual changes seen in this disease.

Chronic oral physostigmine without lecithin improves memory in Alzheimer's disease.

Sixteen patients with early Alzheimers disease (AD) completed a 3‐month outpatient double‐blind parallel trial of oral physostigmine versus placebo. Ten subjects received drug; six received placebo. After a dose‐titration phase, each patient was placed on his or her best dose of drug or placebo. Subjects were evaluated with both memory and nonmemory tasks. Seven of the ten drug‐treated patients, but none of the six placebo‐treated patients, demonstrated improvement on a selective reminding task, a test of verbal memory. Family members reported improvement in six of ten drug‐treated patients and none of six placebo‐treated individuals. There was a trend toward greater improvement with increasing drug dose. There was no improvement on the nonmemory tests administered. The data indicate that oral physostigmine improves memory but not other areas of cognition.

Acute and chronic effects of oral physostigmine and lecithin in Alzheimer's disease

Alzheimer patients were treated with lecithin and gradually increasing doses of oral physostigmine during a drug trial to determine if these compounds would improve memory. Memory was measured using a selective reminding task. Of 16 patients, 10 showed improvement in total recall, retrieval from long-term storage and a decrease in intrusions. The optimal dose was 2.0 mg or 2.5 mg of physostigmine per dose for most patients. During a replication study, all 10 patients again responded. During long-term (4 to 20 months) treatment of five patients, most demonstrated continued drug response initially but then lost responsiveness to physostigmine and their dementia progressed. Physostigmine treatment appeared to improve memory with or without concomitant lecithin therapy. However, progressive dementia ensued despite physostigmine therapy. The degree of memory improvement correlated with increasing cerebrospinal fluid cholinesterase inhibition suggesting that memory improvement is associated with entry of physostigmine into the brain.

Cross-Cultural and Multi-Ethnic Dementia Evaluation by Mental Status and Memory Testing

Two studies investigated aspects of cross-cultural dementia evaluation. The first explored consequences of using different mental status tests; the second compared mental status and memory assessments for normal individuals aged 70-79 and 80-89 in Japan and in America. In a dementia screening clinic, scores from the Hasegawa mental status test could be converted to the Blessed scale without influencing patient classification (impaired vs. unimpaired). Younger subjects were slightly superior to older subjects in mental status in both comparison groups. Both Japanese groups performed better on the memory test than even the younger American group.

Progressive dementia, visual deficits, amyotrophy, and microinfarcts

Data from three patients and 22 previously reported cases suggest that cerebral microinfarction causes a recognizable clinical syndrome. All cases present with stroke, followed by progressive dementia and often with visual field deficits, peripheral vascular disease, and signs of motor neuron dysfunction. The average age at onset is 45, and most patients have been men. Many patients have had valvular or ischemic heart disease; in one of our cases, mitral stenosis caused embolic microinfarcts.

Stages of Retrieval in Verbal Learning.

Abstract Analysis of storage, retention, and retrieval in standard free recall, extended free recall, and repeated recall after a single presentation indicates that most recall failures are retrieval failures, and that extended recall decreases retrieval failure and increases consistent retrieval. Stages of random and consistent retrieval account for total recall in terms of items consistently retrieved from the beginning, items stored for random retrieval, items actually retrieved at random, and additional items reaching the stage of consistent retrieval. The distinction between stages of random and consistent retrieval is supported by showing that random retrieval does not improve prior to the abrupt onset of consistent retrieval. This also indicates that increasing recall is due to the increasing number of consistently retrieved items.