Ellen Grober

Genuine memory deficits in dementia

Controlled learning with effective cued recall is needed to distinguish between genuine memory deficits due to impairment of specific memory processes and apparent memory deficits due to impairment of other cognitive processes, such as attention, that can limit memory. Effective cued recall is needed for accurate measurement of memory in the elderly because cued recall reveals learning not shown by free recall. When a search procedure was used to control processing for effective encoding and cued recall, nondemented elderly adults recalled all or nearly all 16 items on each trial. Decreased recall by demented patients even after they carried out the same effective processing showed genuine memory impairment that was not due to other cognitive deficits. Cued recall was better than either free recall or recognition in discriminating elderly persons with dementia from those without dementia and by itself accounted for 75 % of the variation in dementia status. Cued recall was especially useful for identifying...

Screening for dementia by memory testing

Enhanced cued recall provides a simple and clinically useful memory test for identifying dementia in the elderly. Because this test induces semantic processing and coordinates encoding and retrieval for maximum recall, genuine memory deficits due to impairment of specific memory processes can be distinguished from apparent memory deficits due to use of inefficient strategies or impairment of other cognitive processes. Since genuine memory deficits in the elderly are usually associated with dementia, their identification is highly predictive of clinical dementia. The present study validates the use of enhanced cued recall as a screening test for dementia in 70 aged subjects. All but one person with a pure amnesia were correctly classified. Enhanced cued recall correctly classified 97% of the 120 subjects in this and the previous study. Enhanced cued recall shows learning not revealed by free recall, providing more accurate measurement of memory, and distinguishes demented from nondemented elderly more accurately than either free recall or recognition.

Development and Validation of a Model for Estimating Premorbid Verbal Intelligence in the Elderly

In a preliminary effort to improve the early diagnosis of dementia, we developed a regression-based method for estimating premorbid intelligence measured by the ability to read irregular words from the American version of the Nelson Adult Reading Test (AMNART). Using errors on the AMNART and years of education, a model for predicting current verbal intelligence (VIQ) was developed in a sample of nondemented elderly. Double cross validation showed that the model had high accuracy and stability in estimating current VIQ in nondemented subjects. The model was then used to estimate premorbid VIQ in mildly demented subjects. Estimated premorbid IQ exceeded current IQ by at least 10 points and did not differ from that of nondemented subjects. Less than 10% of nondemented elderly had discrepancies that were as large. If intellectual decline predicts future functional loss and can be reliably measured using cross-sectional data, the requirement of functional impairment may be an unnecessary barrier to the early diagnosis of dementia.

Memory impairment on free and cued selective reminding predicts dementia

Objective: To estimate the relative rates of dementia in initially nondemented subjects with and without memory impairment defined by baseline free recall from the Free and Cued Selective Reminding (FCSR) test. Background: Our approach to identifying persons at high risk for future dementia is to show the presence of memory impairment not caused by other cognitive deficits by using a memory test that controls attention and cognitive processing. When the conditions of testing are not adequately controlled, prediction is reduced because age-associated memory deficits due to other cognitive deficits are confused with dementia-associated memory deficits. Methods: Longitudinal evaluation of 264 initially nondemented, elderly community volunteers from the Einstein Aging Study with clinical and psychometric examinations every 12 to 18 months for up to 10 years. Main Outcome Measures: Dementia was defined by an algorithmic definition that required a Blessed Information Memory and Concentration score >8 and clinical evidence of functional decline. Results: Thirty-two incident cases of dementia developed during follow-up. Survival analyses indicated that subjects with impaired free recall at baseline had dementia develop (relative risk = 75.2, 95% CI = 9.9 to 567) over 5 years of follow-up at dramatically higher rates than subjects with intact free recall after adjusting for age, gender, and education. Conclusion: Poor performance on free recall from FCSR predicts future dementia. These findings support the existence of a preclinical phase of dementia characterized by memory impairment, which is present for at least 5 years before diagnosis.

Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease.

In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence (Nelson, 1982; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimers disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2-3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD.

Memory and mental status correlates of modified Braak staging

We assessed the relationships of performance on memory and mental status tests and neuropathologic stage of Alzheimers disease as defined by Braak and Braak in 29 patients from a prospective clinicopathologic series. We predicted that memory changes would occur at an earlier Braak stage than mental status changes. Staging was accomplished by matching the topographic distribution of neurofibrillary lesions detected with tau immunocytochemistry to the best fitting diagram published by Braak and Braak. Higher Braak stages were associated with decrements in performance on both memory and mental status tests. As predicted, memory performance declined from stages II to III and mental status did not decline until stages III to IV. The association between memory and Braak stage was unchanged after adjusting for neocortical senile plaques, whereas adjustments for Braak stage eliminated the association between cognitive functioning and amyloid burden. We conclude that Braak staging provides a useful summary of Alzheimers disease neuropathology, which is associated with both memory and mental status performance.

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.

Free and Cued Selective Reminding Identifies Very Mild Dementia in Primary Care

The Free and Cued Selective Reminding Test (FCSRT) is used widely to identify very mild dementia; 3 alternative scoring procedures have been proposed based on free recall, total recall, and cue efficiency. We compared the predictive validity of these scoring procedures for the identification of very mild prevalent dementia (CDR=0.5), of incident dementia, and for distinguishing Alzheimer Disease (AD) and nonAD dementias. We tested 244 elderly African American and White primary care patients at 18 month intervals using a screening neuropsychologic battery that included the FCSRT and a comprehensive diagnostic neuropsychologic battery. Median follow-up was 2.6 years. Dementia diagnoses were assigned using standard criteria without access to the results of the screening battery. There were 50 prevalent and 28 incident dementia cases. At scores selected to provide specificities of 90%, free recall was more sensitive to incident and prevalent dementia than the other 2 measures. Patients with impaired free recall were 15 times more likely to have a prevalent dementia and their risk of future dementia was 4 times higher than patients with intact free recall. Neither race nor education affected prediction although older patients were at increased risk of future dementia. Total recall was more impaired in AD dementia than in nonAD dementias. The results indicate that using the FCSRT, free recall is the best measure for detecting prevalent dementia and predicting future dementia. Total recall impairment supports the diagnosis of AD rather than nonAD dementia.

Neuropsychological strategies for detecting early dementia

As new and more effective treatments for Alzheimers disease (AD) emerge, the development of efficient screening strategies in educationally and racially diverse primary care settings has increased in importance. A set of candidate screening tests and an independent diagnostic assessment were administered to a sample of 318 patients treated at a geriatric primary care center. Fifty-six subjects met criteria for dementia. Exploratory analysis led to the development of three two-stage screening strategies that differed in the composition of the first stage or Rapid Dementia Screen, which is applied to all patients over the age of 65. The second stage, applied to those patients who screen positively for dementia, is accomplished with the Free and Cued Selective Reminding Test to detect memory impairment. Using clinical diagnosis as a gold standard, the strategies had high sensitivity and specificity for identifying dementia and performed better for identifying AD than non-AD dementias. Sensitivity and specificity did not differ by race or education. The strategies provide an efficient approach to screening for early dementia.

Sentence comprehension in Alzheimer's disease

A visual sentence‐picture matching task was used to clarify the nature of the comprehension deficit in Alzheimers Disease (AD). Test sentences varied according to how crucial the processing of syntax was in computing a correct interpretation. Half the sentences could be understood through the comprehension of semantic cues alone; the other half required the processing of syntactic cues. In the first experiment, sentences were removed from view before the test pictures were presented; in the second, sentences and pictures were presented together to decrease demands on working memory. Two factors determined the accuracy of sentence comprehension: whether a syntactic analysis was needed and whether additional working‐memory resources were needed for temporary storage. When storage demands were minimized, patients were able to use semantic cues to guide comprehension. When semantic cues were unavailable, comprehension was impaired, regardless of whether or not there were additional storage requirements, prov...