William C. Heindel

Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients

The performances of patients with dementia of the Alzheimer type (DAT), patients with Huntingtons disease (HD), and demented and nondemented patients with Parkinsons disease (PD) were compared on 2 tests of implicit memory that do not require the conscious recollection of prior study episodes: (1) a pursuit-rotor motor learning task and (2) a lexical priming test. The HD patients were found to be impaired on the motor learning but not the lexical priming task, whereas the DAT patients evidenced the opposite relationship on these tasks. The demented, but not the nondemented, PD patients were found to be impaired on both tests of implicit memory. For both the HD and PD patients, deficits on the motor learning task correlated significantly with severity of dementia but not with level of primary motor dysfunction. The noted double dissociation between HD and DAT patients indicates that different forms of implicit memory, all of which are intact in amnesia, are dependent upon distinct neuroanatomic systems. Motor skill learning may be mediated by a corticostriatal system, whereas verbal priming may depend upon the integrity of the neocortical association areas involved in the storage of semantic knowledge. The results for the PD patients suggest that the demented PD patients have endured damage to the neurologic systems subserving both motor learning and lexical priming.

Longitudinal evaluation of dementia of the Alzheimer type: A comparison of 3 standardized mental status examinations

We administered 3 commonly employed tests of mental status (the Information-Memory-Concentration test [IMC], the Mini-Mental State Examination [MMSE], and the Dementia Rating Scale [DRS]) to 92 patients with probable dementia of the Alzheimer type. The 3 tests were readministered to 55 of the patients (2-year subgroup) approximately 1 year later, and administered a 3rd time to 20 of the patients (3-year subgroup) approximately 2 years after their initial assessment. In all cases, scores on the 3 tests were highly correlated with each other. Examination of the annual rate of change (ARC) in score for the 2-year subgroup revealed an average decline of—3.24 error points on the IMC, 2.81 points on the MMSE, and 11.38 points on the DRS. Of the 3 tests, only the DRS evidenced greater sensitivity to change with increasing dementia severity. In the 3-year subgroup, the ARC between years 1 and 2 was not correlated with ARC between years 2 and 3 for any of the 3 tests. This finding suggests that a patients rate of progression in 1 year may bear little relationship to future rate of decline.

A longitudinal study of drivers with Alzheimer disease

Objective: The goal of this study was to define the natural progression of driving impairment in persons who initially have very mild to mild dementia. Methods: We studied 128 older drivers, including 84 with early Alzheimer disease (AD) and 44 age-matched control subjects without cognitive impairment. Subjects underwent repeated assessments of their cognitive, neurologic, visual, and physical function over 3 years. Self-reports of driving accidents and traffic violations were supplemented by reports from family informants and state records. Within 2 weeks of the office evaluation, subjects were examined by a professional driving instructor on a standardized road test. Results: At baseline, subjects with AD had experienced more accidents and performed more poorly on the road test, compared to controls. Over time, both groups declined in driving performance on the road test, with subjects with AD declining more than controls. Survival analysis indicated that while the majority of subjects with AD passed the examination at baseline, greater severity of dementia, increased age, and lower education were associated with higher rates of failure and marginal performance. Conclusions: This study confirms previous reports of potentially hazardous driving in persons with early Alzheimer disease, but also indicates that some individuals with very mild dementia can continue to drive safely for extended periods of time. Regular follow-up assessments, however, are warranted in those individuals.

Neuropsychological deficits associated with driving performance in Parkinson's and Alzheimer's disease

Neuropsychological and motor deficits in Parkinsons disease that may contribute to driving impairment were examined in a cohort study comparing patients with Parkinsons disease (PD) to patients with Alzheimers disease (AD) and to healthy elderly controls. Nondemented individuals with Parkinsons disease [Hoehn & Yahr (H&Y) stage I-III], patients with Alzheimers disease [Clinical Demetia Rating scale (CDR) range 0-1], and elderly controls, who were actively driving, completed a neuropsychological battery and a standardized road test administered by a professional driving instructor. On-road driving ability was rated on number of driving errors and a global rating of safe, marginal, or unsafe. Overall, Alzheimers patients were more impaired drivers than Parkinsons patients. Parkinsons patients distinguished themselves from other drivers by a head-turning deficiency. Drivers with neuropsychological impairment were more likely to be unsafe drivers in both disease groups compared to controls. Compared to controls, unsafe drivers with Alzheimers disease were impaired across all neuropsychological measures except finger tapping. Driving performance in Parkinsons patients was related to disease severity (H&Y), neuropsychological measures [Rey Osterreith Complex Figure (ROCF), Trails B, Hopkins Verbal List Learning Test (HVLT)-delay], and specific motor symptoms (axial rigidity, postural instability), but not to the Unified Parkinson Disease Rating Scale (UPDRS) motor score. Multifactorial measures (ROCF, Trails B) were useful in distinguishing safe from unsafe drivers in both patient groups.

Gender Differences in the Behavioral Manifestations of Alzheimer's Disease

OBJECTIVE: To examine the relationship between gender and specific types of behavior problems that occur in patients with Alzheimers disease.

Maze test performance and reported driving ability in early dementia.

A battery of standard neuropsychological tests examining various features of executive function, attention, and visual perception was administered to 27 subjects with questionable to mild dementia and compared to a 4-point caregiver rating scale of driving ability. Based on the results of this study, a computerized maze task, employing 10 mazes, was administered to a second sample of 40 normal elders and questionable to moderately demented drivers. Comparison was made to the same caregiver rating scale as well as to crash frequency. In the first study of neuropsychological tests, errors on Porteus Mazes emerged as the only significant predictor of driving ability in a stepwise regression analysis. In the follow-up study employing the computerized mazes, all 10 mazes were significantly related to driving ability ratings. Computerized tests of maze performance offer promise as a screening tool to identify potential driving impairment among cognitively impaired elderly and demented drivers. (J Geriatr Psychiatry Neurol 2003; 16:151-155).

Computerized Maze Navigation and On-Road Performance by Drivers With Dementia

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving.

Interactions between phasic alerting and spatial orienting: effects of normal aging and Alzheimer's disease.

The effects of aging and Alzheimers disease (AD) on phasic alerting and exogenous spatial orienting were examined within a single precuing task. Phasic alerting decreased with normal aging and was completely eliminated with AD. AD patients also demonstrated an increased spatial orienting effect, attributable to an increased benefit from spatial orienting that was associated with a decreased benefit from nonselective alerting. These results suggest that performance within the precuing paradigm reflects the product of an interaction between nonselective alerting processes and spatially selective orienting processes. The results also highlight the importance of simultaneously assessing alerting and orienting within the same task, because changes attributable to alerting may otherwise be attributed incorrectly to changes in 1 or more processes associated with spatial orienting.

A single-photon emission computed tomography imaging study of driving impairment in patients with Alzheimer's disease

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer’s disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks.

Neocortical disconnectivity disrupts sensory integration in Alzheimer's disease.

The cortical pathology in Alzheimers disease (AD) should lead to the loss of effective interaction between distinct neocortical areas. This study compared 2 conditions within a single sensory integration task that differed in the demands placed on effective cross-cortical interaction. AD patients were impaired in their ability to bind distinct visual features of a stimulus when this binding placed greater demands on cross-cortical interaction (i.e., motion and color) but were not impaired when this binding placed lesser demands on such interaction (i.e., motion and luminance). In contrast, neurologically intact individuals and patients with Huntingtons disease were able to effectively bind features under both conditions. These results provide psychophysical support for the presence of functional disconnectivity in AD and demonstrate the utility of AD for investigating the neurocognitive substrates of sensory integration.