Nelson Butters

The Lewy body variant of Alzheimer's disease: A clinical and pathologic entity

Thirty-six clinically diagnosed and pathologically confirmed Alzheimers disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.

The HNRC 500-Neuropsychology of Hiv infection at different disease stages

The present study examined neuropsychological (NP) functioning and associated medical, neurological, brain magnetic resonance imaging (MRI), and psychiatric findings in 389 nondemented males infected with Human Immunodeficiency Virus-Type 1 (HIV-1), and in 111 uninfected controls. Using a comprehensive NP test battery, we found increased rates of impairment at each successive stage of HIV infection. HIV-related NP impairment was generally mild, especially in the medically asymptomatic stage of infection, and most often affected attention, speed of information processing, and learning efficiency; this pattern is consistent with earliest involvement of subcortical or frontostriatal brain systems. NP impairment could not be explained on the bases of mood disturbance, recreational drug or alcohol use, or constitutional symptoms; by contrast, impairment in HIV-infected subjects was related to central brain atrophy on MRI, as well as to evidence of cellular immune activation and neurological abnormalities linked to the central nervous system.

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.

Semantic memory impairment in Alzheimer's disease: Failure of access or degraded knowledge?

A battery of neuropsychological tests designed to assess semantic knowledge about the same items both within and across different modalities was administered to a group of 22 patients with dementia of the Alzheimer type (DAT) and 26 matched controls. The DAT patients were impaired on tests of category fluency, picture naming, spoken word-picture matching, picture sorting and generation of verbal definitions. A relative preservation of superordinate knowledge on the sorting and definition tests, as well as a disproportionate reduction in the generation of exemplars from lower order categories was noted. Analysis of the errors made by each patient across the different tests, revealed a significant correspondence between the individual items. These findings offer compelling evidence that the semantic breakdown in DAT is caused by storage degradation.

Cortical Afferents to the Entorhinal Cortex of the Rhesus Monkey

Although the entorhinal cortex is a major contributor of afferents to the hippocampus and dentate gyrus, knowledge of its own afferents has been vague. Regions of both the frontal and temporal lobes were found to contribute afferents to this region of the brain. These afferents form probable multisynaptic links in pathways connecting the classical sensory areas of the cortex and the limbic system.

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

The ability of patients with Huntingtons disease (HD), patients with dementia of the Alzheimers 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.

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.

Patterns of memory failure after scopolamine treatment: implications for cholinergic hypotheses of dementia

To test the idea that scopolamine provides a suitable pharmacological model of the memory defects associated with cortical or subcortical dementias, we assessed memory on a battery of tasks in healthy young normal subjects who received 0.5 mg scopolamine, 0.1-0.2 mg glycopyrrolate or physiological saline, once each on three separate occasions, and compared the pattern of memory failure induced by scopolamine to that observed on the same tasks in patients with Alzheimers disease (AD) or Huntingtons disease (HD). In agreement with previous reports, scopolamine impaired acquisition and delayed recall of a 14-word list and disrupted retention on the Brown-Peterson distractor task, whereas the peripherally active anticholinergic glycopyrrolate was without effect. However, under scopolamine the pattern of errors made on these memory tasks was quite different from that seen in patients with AD. Scopolamine did not increase the number of false positive errors on delayed recognition of the word list and also failed to increase the number of prior-item intrusions on the Brown-Peterson task. Also, scopolamine did not impair learning of a symbol-digit paired-associate task, and did not reduce the number of words retrieved or increase the number of words repeated on a standardized verbal fluency test. When the effects of scopolamine on memory were compared to the pattern of impairments observed in demented patients with HD, several differences were found. Although scopolamine clearly produces deficits on some measures of anterograde memory, the present findings question whether anticholinergic drugs adequately mimic the full range of memory impairments observed in cortical or subcortical dementias.

Episodic memory changes are associated with the APOE- epsilon 4 allele in nondemented older adults

Objective: To compare the memory performances of nondemented older adults with and without the epsilon 4 allele of the apolipoprotein E (APOE- epsilon 4). Background: Few studies have examined the cognitive status of subjects at high risk for the development of dementia of the Alzheimer type (DAT). A newly reported risk factor for DAT allows for an examination of the cognitive performances of nondemented subjects who are at risk by virtue of being either heterozygous or homozygous for the APOE- epsilon 4 allele. Methods: The California Verbal Learning Test (CVLT) was administered to 52 nondemented older adults. Subjects were divided into two groups on the basis of the presence (n equals 17) or absence (n equals 35) of one or two APOE- epsilon 4 alleles. Results: APOE- epsilon 4 and non- epsilon 4 groups did not significantly differ in demographic, mental status, and functional characteristics. APOE- epsilon 4 subjects demonstrated significantly poorer mean performances than non- epsilon 4 subjects on nine CVLT variables. Seven group differences remained significant, and three approached significance (0.05 less than p less than 0.10), after the effects of age and gender were taken into account. Six of the 14 APOE- epsilon 4 subjects who completed annual follow-up evaluations developed either DAT or questionable DAT, whereas none of the 26 non- epsilon 4 subjects who received follow-up demonstrated any cognitive decline. Conclusions: Results suggest that episodic memory changes in older adults are associated with APOE- epsilon 4 allele; sensitive cognitive markers such as those of the CVLT may precede the subsequent development of DAT. NEUROLOGY 1995;45: 2203-2206

Memory Dysfunction and Word Priming in Dementia and Amnesia

Memory performance of patients with the clinical diagnosis of Alzheimers disease was compared with performance of patients with alcoholic Korsakoffs syndrome and patients with Huntingtons disease. Although all patient groups exhibited impairment on tests of verbal memory, only patients with Alzheimers disease exhibited impaired priming. Priming is an unconscious expression of recently encountered material, and it is intact even in severely amnesic patients. Because mildly demented patients with Alzheimers disease exhibited impaired priming, damage to brain structures in addition to those damaged in the amnesic syndrome must occur at a relatively early stage of the disease process.