Retrograde amnesia in patients with Alzheimer's disease or Huntington's disease.

Retrograde amnesia (RA) was studied in patients with Huntington's disease (HD) or Alzheimer's disease (AD) using an updated version of the remote memory battery originally developed by Albert, Butters and Levin. Regardless of whether remote memory was measured by unaided recall or cued recall, HD patients exhibited deficits that were equally severe across decades. RA was more severe in AD than in HD patients and the AD patients recalled significantly more items from the 1940s and 50s than from the 60s, 70s or 80s. The AD patients also displayed dysnomia, while the HD patients did not. Naming difficulties appeared to contribute to the poor overall performance of the AD patients, but did not account for the temporal gradient of their RA. These findings, like recent reports focusing on these patients' ability to learn new information and to search semantic memory, indicate that the processes underlying AD and HD patients' memory failures are distinct.

Differentiation of Alzheimer's disease and Huntington's disease with the Dementia Rating Scale.

Patients with dementia of the Alzheimer type (DAT) and Huntington's disease (HD) were assessed with the Dementia Rating Scale, a brief mental status examination that provides a global dementia score and subtest scores for attention, initiation, construction, conceptualization, and memory capacities. Although the patients with DAT and the patients with HD were precisely matched in terms of total Dementia Rating Scale score, different subtest score profiles emerged. Patients with DAT were more impaired than patients with HD on the Memory subtest, whereas patients with HD were more impaired than patients with DAT on the initiation subtest. These results are indicative of qualitative differences in the cognitive impairment of the two disorders and demonstrate that such differences can be elucidated with brief mental status examinations.

The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection.

OBJECTIVE: To directly examine the relationship between magnetic resonance imaging (MRI) abnormalities and neuropathologic changes in the brains of patients with the acquired immunodeficiency syndrome. DESIGN: A total of 17 brains from patients with acquired immunodeficiency syndrome for which postmortem MRI scans were available were used in this study. Volumes of cortical gray matter, deep gray matter, and abnormal white matter were estimated from the MRIs of the left hemispheres of the formalin-fixed brains from patients with acquired immunodeficiency syndrome using quantitative morphometric techniques. Quantitative estimates of human immunodeficiency virus, gliosis, and neocortical synaptic and dendritic density were obtained from the corresponding right hemispheres. Quantification of human immunodeficiency virus and gliosis was performed on all 17 specimens, while quantification of synaptic and dendritic density was performed on 10 of the 17 specimens. SETTING: All specimens were obtained from patients with the acquired immunodeficiency syndrome who underwent autopsy between 1990 and 1992 at the University of California-San Diego Medical Center and the San Diego (Calif) Department of Veterans Affairs Hospital. RESULTS: No association was found between MRI volumes and gliosis, a nonspecific marker of central nervous system damage. Significant and regionally specific relationships were obtained, however, between the severity of central nervous system human immunodeficiency virus infection and the MRI volume estimates of gray matter and abnormal white matter. In addition, a significant association was observed between cortical gray matter volumes and cortical synaptic density. CONCLUSION: These findings indicate that the quantitative morphometric analysis of MRIs in patients may provide sensitive in vivo markers of neuropathologic changes associated with human immunodeficiency virus infection of the brain.

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 patient's rate of progression in 1 year may bear little relationship to future rate of decline.

Non-associative lexical priming is impaired in Alzheimer's disease.

A word-fragment completion task was used to assess long-term, non-associative lexical priming in patients with probable Alzheimer's disease (AD) and age- and education-matched elderly normal control (NC) subjects. Despite equivalent baseline performance, the AD patients exhibited less facilitation in their ability to complete word fragments from having previously read the intact words than did the NC subjects. The AD patients were also impaired relative to NC subjects on an explicit recognition memory task, but there was no relationship between explicit memory performance and priming for either group. These results are consistent with previous demonstrations of impaired semantically-based priming in patients with AD and extend the domain of their impairment to priming that is predominantly based on lexical activation.

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 Alzheimer's disease. DESIGN: This was an observational study using the Dementia Behavior Disturbance Scale to quantify and define behavioral problems encountered by caregivers. Multiple regressions were used to control for the possible influence of dementia severity as measured by the Mini-Mental State Examination and the duration of dementia. SETTING: Patients were sampled from the outpatient dementia clinics of Roger Williams Hospital and Miriam Hospital in Providence, Rhode Island. PARTICIPANTS: A total of 125 patients with probable Alzheimer's disease, defined by NINCDS-ADRDA diagnostic criteria, were included in the study. There were 75 women and 50 men. MAIN OUTCOME MEASURES: Caregivers rated the presence and frequency of 28 different behavior problems from the Dementia Behavior Disturbance Scale. Domains of behavior disturbance were then defined by a factor analysis of the data. RESULTS: Male and female groups were comparable for the demographic variables of age, education, and duration of dementia, as well as severity of depression, degree of cognitive impairment and overall severity of behavior disturbance. Among the six behavior factors that were defined, two were significantly related to gender. One factor, which included apathy and vegetative signs, was related to male gender; a second factor, which included reclusiveness and emotional lability, was related to female gender. CONCLUSIONS: Although overall severity of behavior disturbance in Alzheimer's disease may be related primarily to severity in dementia, significant differences in the types of behaviors manifested exist between males and females with the disease.

Impaired learning of a motor skill in patients with Huntington's disease.

The ability of patients with Huntington's disease (HD), patients with dementia of the Alzheimer's type (DAT), and amnesic patients (AMN) to acquire the motor skills underlying a pursuit rotor task was assessed. Differences between groups in initial levels of performance were minimized by adjusting the rotation speed of the disk. The HD and DAT groups were also administered a verbal recognition span test. The results showed that the DAT, AMN, and intact control groups all significantly improved their time on target over six test blocks whereas the HD group was severely impaired in the acquisition of this motor skill. On the verbal recognition span test, the DAT and HD groups were significantly and equally impaired, but the HD group evidenced better immediate and delayed recall than did the DAT group. These results provide further evidence that the basal ganglia are critically involved in the acquisition of motor skills.

Repetition priming with nonverbal stimuli in patients with dementia of the Alzheimer type.

Perceptual repetition priming was examined in patients with dementia of the Alzheimer type (DAT) and normal control (NC) participants using a task involving the discrimination of geometric designs that had either a continuous ("closed") or discontinuous ("open") perimeter. With the open stimuli, the groups displayed significant and equivalent levels of priming after immediate repetition of the stimuli, whereas only the NC group primed significantly over a delay of three intervening items. Neither group demonstrated significant priming with the closed stimuli. Results indicate that under some conditions DAT patients can exhibit normal repetition priming with stimuli that do not have preexisting representations but that (due possibly to a deficiency in the level of steady-state cortical activation) this priming dissipates more rapidly in DAT patients than in NC participants.

Dispositional correlates of hypnosis: a phenomenological approach.

An attempt was made to construct and validate a questionnaire measure of hypnotic-like experiences based on Shor's (1979) 8-dimension phenomenological analysis of hypnosis. Separate item pools were developed to measure each disposition: Trance, Nonconscious Involvement, Archaic Involvement, Drowsiness, Relaxation, Vividness of Imagery, Absorption, and Access to the Unconscious. Based on preliminary testing (total N = 856), a final questionnaire was produced containing 5 items measuring normal, everyday experiences in each domain. Results from a standardization sample (N = 468) showed that each of the subscales, except for Archaic Involvement, possessed satisfactory levels of internal consistency and test-retest reliability. Factor analysis indicated that 6 subscales loaded highly on a common factor similar to the absorption construct (Tellegen & Atkinson, 1974), while items pertaining to Relaxation and Archaic Involvement formed separate factors. Validation testing on 4 samples receiving the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) of Shor and E. Orne (1962) (total N = 1855) showed that the Absorption and Trance dimensions correlated most strongly with HGSHS:A; the correlations with Drowsiness, Relaxation, and Nonconscious Involvement approached 0. The scales derived from Shor's analysis, however, did not improve the prediction of hypnotizability over that obtained with the absorption scale (Tellegen & Atkinson, 1974).

Specificity of the memory deficits associated with basal ganglia dysfunction.

Recent studies comparing the explicit and implicit memory disorders of Huntington's disease (HD) and Alzheimer's disease (AD) patients have yielded new insights into the specificity of the memory disorders associated with basal ganglia dysfunction. Patients with HD have severe deficiencies in retrieving information from either episodic or semantic explicit memory. This retrieval deficit is not confounded by impairments in storage, rapid forgetting, intrusion errors and a deterioration of the structure of semantic knowledge. While HD patients perform normally on implicit memory tasks involving lexical, semantic and pictorial priming, they are impaired on implicit tests which require the initiation and/or modification of central motor programs. It is concluded that the basal ganglia play a specific but important role in memory although the processes they mediate are different from those dependent on the integrity of the hippocampus and diencephalon.

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.

Memory systems in normal and pathological aging.

Normal memory depends on a number of interdependent systems whose specialized contributions are dissociable at both cognitive and neurobiological levels of analysis. Guided by this multiple systems view of memory, this review provides a selective survey of recent studies on cognitive and neurobiological aging. Taken together, the results suggest that memory decline in human aging partly reflects a compromise of executive memory processes supported by frontal lobe regions of the brain, combined with a deterioration of explicit memory capacities supported by the hippocampal system. Defining how deficits in multiple memory systems interact to account for cognitive aging remains a significant challenge.

Pictorial priming and cued recall in Alzheimer's and Huntington's disease.

A picture fragment test was used to compare the priming and cued recall performances of patients with Huntington's disease (HD), patients with dementia of the Alzheimer type (DAT), and neurologically intact normal control (NC) subjects. On the pictorial priming test, subjects were asked to say "the first thing you think of" when shown incompletely drawn pictures, half of which were previously exposed to the subject during an unrelated naming task. Normal controls and HD patients, but not DAT patients, demonstrated similar increases in their ability to identify fragmented versions of previously seen pictures relative to novel pictures. These results are consistent with the previously observed pattern of preserved and impaired verbal priming ability in HD and DAT patients, respectively. The NC subjects, as expected, also demonstrated better performance on the cued recall than on the priming version of the picture fragment test, whereas the HD patients evidenced the opposite relationship on these two tasks and DAT patients were found to be equally impaired on both tests. This finding provides further support for the notion that HD patients' memory impairment is characterized primarily by an inability to initiate systematic retrieval strategies.

Sensorimotor disinhibition in Parkinson's disease: effects of levodopa.

It has been known for some time that patients with Parkinson's disease (PD) have difficulty executing simultaneous motor acts, yet the pathophysiology underlying this impairment remains uncertain. We examined the possibility that these dual-task deficits stem from defective sensorimotor mechanisms producing interference between the motor programs underlying the two tasks. Patients with PD and normal control subjects were tested on their ability to maintain steady-state force with one hand while performing a force-reaction time task with the other hand. Although performance was worse on the dual-task than on the single-task condition for both subject groups, only the patients with PD demonstrated significant interference between the two tasks. The interference across tasks improved in 87% of the patients with PD when tested after treatment with carbidopa/levodopa (Sinemet). These findings support the contention that, in patients with PD, disturbances in the execution of simultaneous motor performance may be due to sensorimotor disinhibition.

The biasing of weight judgments in Alzheimer's and Huntington's disease: a priming or programming phenomenon.

The performances of Huntington's disease (HD) patients and patients with dementia of the Alzheimer type (DAT) were compared on an adaptation-level task involving the judgment of weights. In this task, subjects were first exposed to either a relatively heavy (heavy bias) or a relatively light (light bias) set of weights, and were later asked to rate the heaviness of a standard set of 10 weights using a 9-point scale. Patients with DAT and intact control subjects both perceived the standard set of weights as heavier following the light bias trials and lighter following the heavy bias trials, despite the DAT patients' poor explicit memory for the initial biasing session. In contrast, the weight judgments of the HD group as a whole was not significantly influenced by prior exposure to relatively heavy or light weights, and the size of the bias effect for this group was significantly correlated with the severity of their dementia. It is suggested that the impaired biasing performance of the HD patients, like their previously demonstrated impairment in motor skill learning, is due to a motor programming deficit resulting from neostriatal dysfunction.

The biasing effect of verbal labels on memory for ambiguous figures in patients with progressive dementia.

This experiment investigated the effects of verbal labels on recognition memory for ambiguous visual figures in patients with Alzheimer's disease (AD), patients with Huntington's disease (HD), and matched normal control subjects. The study employed ambiguous figures that could be interpreted in two different ways. During the study phase each figure was presented together with a verbal label that corresponded to one interpretation of the figure. After a 30-min retention interval a recognition memory test was given during which the study figures and distractor figures were presented one at a time without verbal labels. For each study figure two distractor figures were employed, each corresponding to a different interpretation of the study figure. The patients' overall recognition memory performance was severely impaired compared to control subjects. However, all subject groups tended to produce responses and response latencies to distractor items that were consistent with the verbal labels presented during the study phase. This bias effect occurred in the AD patients despite the fact that their recognition memory performance was at chance level. Indeed, there was no significant difference in the bias evidenced by the AD and HD patients and their respective matched control subjects. The bias effects were obtained in an explicit memory task, and the findings are discussed in terms of unconscious influences on explicit memory processes.

Differential decline in word generation from phonemic and semantic categories during the course of Alzheimer's disease: implications for the integrity of semantic memory.

The ability to generate words from phonemic (i.e., words beginning with 'F,' 'A,' and 'S') and semantic (i.e., animals, fruits, and vegetables) categories was assessed longitudinally in patients with Alzheimer's disease (AD; N = 59) and normal controls (NC; N = 59). Patients with AD performed worse than NC participants on both tasks at each of 4 annual evaluations and exhibited greater impairment relative to controls on the semantic-category task than on the phonemic-category task. In addition, the performance of the patients with AD declined over time on both tasks, but the rate of decline was faster on the semantic-category than on the phonemic-category task. Examination of individual responses across the annual evaluations revealed that patients with AD were more consistent than NC participants in failing to generate previously produced semantic-category, but not phonemic-category, items in all years following the 1st year in which the item was not produced. These results are consistent with the notion that patients with AD suffer a gradual deterioration of the organization and content of semantic memory as the disease progresses.

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 Huntington's disease (HD), and demented and nondemented patients with Parkinson's 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.

Lateralized cortical perfusion in women with Alzheimer's disease.

OBJECTIVE: To define the pathophysiologic substrate of gender differences in cognition and behavior in Alzheimer's disease (AD). DESIGN: Hemispheric regional cerebral blood flow (rCBF) was studied in a consecutive series of dementia patients using single photon emission computed tomography (SPECT). PARTICIPANTS: Subjects included 300 outpatients who were studied with SPECT as part of a diagnostic evaluation for degenerative dementia or memory disorder. METHOD: Based on qualitative descriptions by a radiologist, subjects were classified as having unilateral left, unilateral right, bilateral, or no perfusion defects. Semiquantitative analysis of SPECT images was also performed using region of interest radionuclide counts normalized to the cerebellum. RESULTS: Among 174 females and 126 males, unilateral left hemisphere defects were found more commonly in women than men (24% vs 10%; chi 2 = 9.4; P = .009). This observation was most significant for the 103 females and 62 males regarded as having probable AD (26% vs 8%; chi 2 = 9.3; P = .01). In a multiple regression model of clinical variables, shorter duration of disease and female gender were significant independent predictors of the unilateral left hemisphere pattern among those with probable AD. Age, family history, education, handedness, and severity of cognitive impairment were not significant contributors. CONCLUSIONS: Women with AD exhibit greater heterogeneity in rCBF than men. Asymmetry in rCBF occurs more often in women. In some cases, this is related to relative preservation of right hemisphere function in women.

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.