Luigi Galvani, body electricity, and the 'galvanic skin response'.
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Galvanic Skin Response↗
Biomedical subjects
F Boller
Publications and source records attributed to F Boller.
Neuropsychological function in Alzheimer's disease. Pattern of impairment and rates of progression.
Although patients with Alzheimer's disease (AD) generally have impairments in multiple areas of cognitive function, there are those patients who appear to have neuropsychological deficits more prominent in one domain than in other domains. We examined the neuropsychological status of 86 patients with probable AD and 92 elderly control subjects and identified the patterns of impairments in the patients with AD. Independent deficits of visuoconstructional and lexical/semantic abilities were identified in a subset of patients by a principal components analysis. Individual patients were identified who were predominantly impaired in one, but not the other, neuropsychological domain. There were no striking relationships between the demographic characteristics of the patients and their pattern of deficits at the initial evaluation. There were no significant differences in age at onset or rate of progression of dementia among patients with different patterns of cognitive dysfunction. A review of the results of this and other studies suggests that the language impairment in AD may be associated with two distinct neuropsychological abnormalities: a lexical/semantic impairment that is unrelated to onset or progression of symptoms, and a syntactic impairment that may be associated with earlier onset and more rapid progression of dementia.
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Correlation of phosphorus-31 magnetic resonance spectroscopy and morphologic findings in Alzheimer's disease.
Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.
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The use of phonemic cueing with Alzheimer's disease patients.
Variables influencing responsiveness to phonemic cueing, although studied extensively in the aphasia population, have not been identified in the Alzheimer's disease population. In this study, four variables were analyzed in relation to successfulness of phonemic cueing: severity of dementia, confrontational naming ability, auditory comprehension, and speech fluency. All three language measures showed a significant positive correlation with cueing. Severity of dementia showed a significant inverse correlation with responsiveness to cueing and was the best predictor of successful use of cueing. It was concluded that phonemic cueing aided in label retrieval, problematic in the early stages of Alzheimer's disease, prior to significant erosion of semantic meaning.
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Risk of dementia in relatives of patients with Alzheimer's disease.
Using a family history questionnaire, we investigated the occurrence of dementia among relatives of patients with a clinical diagnosis of Alzheimer's disease (AD) and among the relatives of age-matched control subjects. Cumulative lifetime risk of developing AD-type dementia was greater among relatives of AD probands and was consistent with an autosomal dominant genetic mode of transmission. Although the lifetime risk of AD-type dementia was similar among relatives of early-onset and late-onset AD probands, relatives of early-onset probands tended to have an earlier onset of dementia than did relatives of late-onset AD probands. This result raises the possibility that age at onset of dementia in AD may be genetically determined.
Actuarial Analysis↗
Family study of platelet membrane fluidity in Alzheimer's disease.
The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup of patients with Alzheimer's disease who manifest distinct clinical features. In a family study, the prevalence of this platelet membrane abnormality was 3.2 to 11.5 times higher in asymptomatic, first-degree relatives of probands with Alzheimer's disease than in neurologically healthy control subjects chosen without regard to family history of dementia. The pattern of the platelet membrane abnormality within families was consistent with that of a fully penetrant autosomal dominant trait. Thus, this abnormality of platelet membranes may be an inherited factor that is related to the development of Alzheimer's disease.
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Learning deficit in Parkinson's disease. Comparison with Alzheimer's disease and normal aging.
The learning ability of 12 patients with Parkinson's disease (PD) was studied using a verbal paired-associate learning task, and was compared with that of ten patients with Alzheimer's Disease (AD) and 12 controls (NC). Overall, the PD patients performed significantly better than the AD patients but significantly worse than the NC subjects. Their performance was not related to their overall level of cognitive functioning as measured by the Mattis' Dementia Rating Scale, but was unequally distributed suggesting that the PD population actually consisted of more than one subgroup. A low error group performed like controls, while a high error group had a learning impairment comparable to that of AD patients. It is concluded that PD patients may have three patterns of neuropsychologic performance: some are unimpaired, some have "focal" abnormalities, and some have a generalized impairment of cognitive function.
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Thalamic and subcortical gliosis with dementia.
We describe two cases of patients with "primary dementia" in whom autopsy showed marked astrocytosis in several subcortical nuclei, but chiefly in those of the thalamus. One patient had the onset of symptoms at 31 years of age and a subacute course. The second patient was an elderly man with a strong familial history of dementia. These cases offer further evidence that subcortical lesions, especially in the thalamus, may produce a dementia that is not always clinically distinguishable from Alzheimer's disease and other "cortical" dementias.
Adult↗
The neurologic examination in patients with probable Alzheimer's disease.
Abnormal findings on a standardized neurologic examination were compared between patients with a clinical diagnosis of probable Alzheimer's disease (AD) and healthy control subjects. Aside from mental status findings, the most useful examination findings for differentiating AD from control subjects were the presence of release signs, olfactory deficit, impaired stereognosis or graphesthesia, gait disorder, tremor, and abnormalities on cerebellar testing. These abnormalities probably reflect the different areas of the central nervous system that are affected pathologically in AD. In the clinical diagnosis of AD, particular attention should be given to these aspects of the neurologic examination.
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A controlled study of survival with dementia.
Widely conflicting data exist regarding the relationship of dementia to mortality and the relative risk of senile dementia of the Alzheimer type vs multi-infarct dementia with respect to mortality. In a historic prospective study, 202 patients with dementia were matched by age and sex with 202 nondemented controls attending the same geriatric assessment clinic and receiving comparable medical and psychiatric care. The three-year survival rate was 70% for patients with dementia and 84% for controls. Patients with multi-infarct dementia survived more poorly than patients with senile dementia of the Alzheimer type, but the difference did not reach statistical significance. The relative risk associated with dementia in the context of a multivariate analysis was 1.92 (95% confidence [1.25, 2.97]). We conclude that dementia carries a significantly increased risk of mortality but that the survival of patients with dementia may be better than previous reports would suggest.
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Platelet membrane abnormality in Alzheimer's disease.
Fluorescence studies of membrane fluidity were conducted double-blind using platelet and red cell membranes prepared from 24 demented patients with probable Alzheimer's disease and 36 neurologically healthy subjects. The fluidity of the hydrocarbon and lipid-aqueous interface regions of cell membranes was determined at 37 degrees C by fluorescence spectroscopy using the lipid probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), respectively. The rotation rate of TMA-DPH in labeled platelet membranes did not differ between the groups. In contrast, the rotation rate of DPH in labeled platelet membranes from the demented patients (2.15 +/- 0.24 X 10(8)/sec, SD) was greater than that for the normal controls (1.93 +/- 0.13 X 10(8)/sec, SD, p = 3.8 X 10(-5)). This difference was reflected by a reduction in the steady-state anisotropy of DPH in labeled platelets from the demented group (0.1887 +/- 0.0085, SD) when compared to the respective mean for the controls (0.2000 +/- 0.0060, SD; p = 1.3 X 10(-7)). Abnormal membrane fluidity was significantly correlated with severity of dementia, but not with duration of illness or apparent age of onset. The findings do not support the hypothesis that Alzheimer's disease results from a pathological acceleration of the normal aging process, since normal aging is associated with decreased fluidity of cell membranes from platelets, as well as from lymphocytes, hepatocytes, and neurons.
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Platelet membrane fluidity identifies a clinical subtype of Alzheimer's disease.
1. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup (approx. 50%) of patients with Alzheimer's disease who manifest distinct clinical features. 2. We review an integrated series of studies that explore both the clinical significance of this finding and the biological basis for the platelet membrane alteration.
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Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease.
Recent work has suggested that patients with damage to temporal lobe structures, such as patients with Alzheimer's Disease (AD), lose information from memory at an abnormally rapid rate. In contrast, data from other studies suggest that the rate of forgetting in AD is normal. In the present study, 62 patients with mild to moderate AD and 64 elderly controls were tested for their immediate and delayed recall of a short verbal passage and a modified Rey complex figure. The results suggest that although AD patients recalled less than controls, they did not forget at a faster rate during the 30 minute retention interval, supporting the finding that these memory impaired patients do not have an abnormal rate of forgetting. The data also suggest that poor initial encoding of the stimuli may be the cause of the AD patients' impaired recall.
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The use of language structure by demented patients in a visual search task.
Recent findings suggest that some components of semantic memory are spared by Alzheimer's disease. The present study used a visual-search task to determine whether knowledge of the sequential letter dependencies present in spelling remains intact in demented patients. The speed with which twenty Alzheimer patients, twenty young and twenty old controls searched an array of letters for a target was measured. Arrays varied in how closely they approximated English-spelling patterns (zero-order, and third-order approximations and actual words). Despite differing in their overall speed of response, normal and demented subjects were affected equally by the approximation to English of the stimuli (i.e., both searched words faster than low-order approximations). Thus, knowledge of the probability patterns of spelling appears to remain intact and accessible in the semantic memory of demented patients.
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Platelet membrane fluidity in Alzheimer's disease and major depression.
Double-blind fluorescence studies of platelet membrane fluidity were conducted at 37 degrees C for 51 patients with Alzheimer-type dementia, 24 nondemented depressed patients, and 50 neurologically healthy subjects. The fluidity of the hydrocarbon region of platelet membranes from the demented group, as reflected by the steady-state anisotropy of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was significantly greater than that for the depressed and normal control subjects. Within the demented group, platelet membrane fluidity was significantly correlated with severity of dementia but not with duration of illness or age at onset. Demented patients with "increased" platelet membrane fluidity had an earlier onset, were more severely demented, and deteriorated more rapidly.
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Lack of heart rate changes during an attention-demanding task after right hemisphere lesions.
Patients with right hemisphere lesions may be impaired in mobilizing attention and in emotional behavior. If so, autonomic responses to the mobilization of attention should be blunted. This was found when we studied the anticipatory heart rate deceleration that is seen normally in the foreperiod of a warned reaction task.
Adult↗
Cognitive deficits and clinical diagnosis of Alzheimer's disease.
We used cognitive deficits detected by neuropsychological testing to evaluate clinical diagnosis of Alzheimer's disease. Deficits were defined with respect to performance of control subjects according to procedural guidelines set by a NINCDS-ADRDA Work Group. The most frequent deficits were in recent memory and lexical-semantic language abilities. Clinical diagnosis of Alzheimer's disease was compared with diagnosis based on a criterion of two or more cognitive deficits both on initial neuropsychological testing and on testing repeated a year later in some subjects. Initial clinical diagnosis identified 96% of cases who met the criterion when first tested and 100% of those with multiple deficits at follow-up. Specificity with respect to the criterion was 86% on initial testing and 89% at follow-up. These findings support the validity of clinical diagnosis of Alzheimer's disease using the NINCDS-ADRDA criteria.
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Clinical prediction rules for computed tomographic scanning in senile dementia.
The role of computed tomography (CT) of the head in evaluating patients with dementing illnesses remains a controversial issue. Several prediction rules to guide the selective application of CT in the evaluation of dementia have recently been proposed in the medical literature. The present authors examine the value of four such rules through a validation study performed in an outpatient geriatric assessment unit. The rules were assessed in terms of their diagnostic sensitivities, specificities, misclassification rates, and information contents. Prediction rule sensitivities ranged from 12.5% to 87.5%, specificities from 37.2% to 77.9%, and misclassification rates from 23.5% to 60.8%. Of the four prediction rules examined, one emerged as significantly more sensitive than the others, and also served to reduce diagnostic uncertainty a full order of magnitude more than the others, as determined by an information content analysis. Disadvantages to this rule, however, were found in its more complex nature and the assessment of a very high rate of misclassification. Through a critique of existing strategies, this study purports to determine the potential for establishing a useful clinical prediction rule to guide selective CT scanning in the diagnostic evaluation of dementia.
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