Eric Steinberg

Lower-Extremity Function in Cognitively Healthy Aging, Mild Cognitive Impairment, and Alzheimer's Disease

OBJECTIVE To examine differences in lower-extremity function in cognitive healthy older persons, older persons with mild cognitive impairment (MCI), and older persons with Alzheimers disease (AD). DESIGN Descriptive study. SETTING University Alzheimers disease clinical and research program. PARTICIPANTS Older persons (N=66) were studied (mean age, 76.7y); 22 were cognitively normal, 22 were diagnosed with probable MCI, 22 were diagnosed with probable AD. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Lower-extremity function was assessed by the four-meter walk test (4MWT), Timed Up & Go (TUG) test, and sit-to-stand (STS) test. RESULTS Analysis of variance, adjusting for covariates, revealed that performance on the 4MWT was significantly lower in the MCI and AD groups as compared with controls. TUG test performance was worse in the AD group compared with controls. No significant group differences were found for STS performance. CONCLUSIONS These results suggest an association between cognitive impairment and lower-limb function in older persons. Walking speed could be evaluated for its possible utility in screening older persons at risk for cognitive impairment and falls.

Clock Drawing Test Ratings by Dementia Specialists: Interrater Reliability and Diagnostic Accuracy

The authors conducted a study of clock drawing test scoring by dementia specialists to determine interrater reliability and diagnostic accuracy. The authors randomly assigned 25 clocks from each of six predetermined groups based on consensus diagnosis (cognitive comparison subjects, subjects with a memory complaint but with normal neuropsychological testing, subjects with probable and possible mild cognitive impairment, and subjects with possible and probable Alzheimers disease) to dementia specialists for blinded scoring using a binary yes/no impairment system and a 0-10 scale as subjectively determined by each individual clinician rater. The authors collapsed the six groups into three (comparison subjects, mild cognitive impairment patients, and Alzheimers disease patients) and analyzed interrater reliability, sensitivity, and specificity for consensus diagnosis of mild cognitive impairment and Alzheimers disease. The authors found excellent interrater reliability, sensitivity, and specificity for predicting consensus diagnosis. The 0-10 clock drawing test rating scale was more predictive of consensus diagnosis than the binary impairment scale. Based on rating systems, clock drawing test scoring by dementia clinicians had excellent interrater reliability and sensitivity for differentiating the mild Alzheimers disease subjects from comparison subjects.

Mini Mental State Examination and Logical Memory scores for entry into Alzheimer’s disease trials

BackgroundSpecific cutoff scores on the Mini Mental State Examination (MMSE) and the Logical Memory (LM) test are used to determine inclusion in Alzheimer’s disease (AD) clinical trials and diagnostic studies. These screening measures have known psychometric limitations, but no study has examined the diagnostic accuracy of the cutoff scores used to determine entry into AD clinical trials and diagnostic studies.MethodsClinicalTrials.gov entries were reviewed for phases II and III active and recruiting AD studies using the MMSE and LM for inclusion. The diagnostic accuracy of MMSE and LM-II cutoffs used in AD trials and diagnostic studies was examined using 23,438 subjects with normal cognition, mild cognitive impairment (MCI), and AD dementia derived from the National Alzheimer’s Coordinating Center database.ResultsMMSE and LM cutoffs used in current AD clinical trials and diagnostic studies had limited diagnostic accuracy, particularly for distinguishing between normal cognition and MCI, and MCI from AD dementia. The MMSE poorly discriminated dementia stage.ConclusionsThe MMSE and LM may result in inappropriate subject enrollment in large-scale, multicenter studies designed to develop therapeutics and diagnostic methods for AD.

Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer’s Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.

Practice Effects on Story Memory and List Learning Tests in the Neuropsychological Assessment of Older Adults

Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechslers Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimers disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed—but not the immediate—recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants—but not participants with AD—improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects—especially on the delayed recall condition—suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis.

Clinical Utility of Select Neuropsychological Assessment Battery Tests in Predicting Functional Abilities in Dementia

Objective Neuropsychological test performance can provide insight into functional abilities in patients with dementia, particularly in the absence of an informant. The relationship between neuropsychological measures and instrumental activities of daily living (IADLs) is unclear due to hetereogeneity in cognitive domains assessed and neuropsychological tests administered. Practical and ecologically valid performance-based measures of IADLs are also limited. The Neuropsychological Assessment Battery (NAB) is uniquely positioned to provide a dual-purpose assessment of cognitive and IADL function, as it includes Daily Living tests that simulate real-world functional tasks. We examined the utility of select NAB tests in predicting informant-reported IADLs in mild cognitive impairment and dementia. Methods The sample of 327 participants included 128 normal controls, 97 individuals with mild cognitive impairment, and 102 individuals with Alzheimers disease dementia from the Boston University Alzheimers Disease Center research registry. Informants completed the Lawton Brody Instrumental Activities of Daily Living Scale, and study participants were administered selected NAB tests that were complementary to the existing protocol. Results ROC curves showed strongest prediction of IADL (AUC > 0.90) for memory measures (List Learning delayed recall and Daily Living Memory delayed recall) and Daily Living Driving Scenes. At a predetermined level of specificity (95%), List Learning delayed recall (71%) and Daily Living Memory delayed recall (88%) were the most sensitive. The Daily Living Memory and Driving Scenes tests strongly predicted IADL status, and the other Daily Living tests contributed unique variance. Conclusions NAB memory measures and Daily Living Tests may have clinical utility in detecting informant-rated functional impairment in dementia.

HIPPOCAMPAL VOLUME AND FUNCTIONAL CONNECTIVITY DIFFERENTIATE BETWEEN COGNITIVELY NORMAL INDIVIDUALS WITH AND WITHOUT SUBJECTIVE MEMORY COMPLAINTS

relationships between hippocampal volume obtained by 7T MRI and memory function were observed in clinically healthy older adults. Since weak associations were also found in the control region, volumes of other cortical brain regions will be analyzed to exclude a global effect. Further analyses will include APOE ε4 carrier status to test if negative associations are restricted to individuals at high risk for AD. Ongoing analyses will also include patients diagnosed with mild cognitive impairment and AD.