[Neuropsychological theories of frontal lobe function].
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Behavior↗
Biomedical subjects
E L Helkala
Publications and source records attributed to E L Helkala.
Slowing of the dominant occipital rhythm in electroencephalogram is associated with low concentration of noradrenaline in the thalamus in patients with Alzheimer's disease.
The thalamus is involved in the regulation of the neocortical rhythmicity reflected in EEG as the alpha rhythm. Recent evidence suggests that the thalamus is affected in Alzheimer's disease (AD). We studied the relationship between the dominant occipital rhythm of the lifetime EEG and the choline acetyltransferase activity (ChAT) and monoamine concentrations in the postmortem thalamus of 20 histologically verified AD patients. The AD patients were divided into 3 groups (5-6 Hz, 7 Hz and 8-9 Hz) according to the frequency of the dominant occipital rhythm (FOC). Noradrenaline (NA) concentrations were significantly lower for the 5-6 Hz and 7 Hz subgroups as compared to the 8-9 Hz subgroup. The NA content of the thalamus correlated significantly with the FOC (r = 0.46, P = 0.04). The ChAT activity or concentrations of dopamine or serotonin did not correlate with the FOC or differ across the AD subgroups. The results suggests that the noradrenergic deficit of the thalamus may contribute to slowing of the dominant occipital rhythm in AD.
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Extrapyramidal signs in Alzheimer's disease: a 3-year follow-up study.
Occurrence of extrapyramidal signs was investigated in a follow-up study of 32 patients with probable Alzheimer's disease (AD). Bradykinesia and rigidity were observed in 39% and 11% of the neuroleptic-free patients at entry and in 72% and 61% at year 3, respectively. Tremor was not a predominant feature nor did its occurrence increase over time. Use of neuroleptics contributed to extrapyramidal signs; 75-100% of the neuroleptic-treated patients showed bradykinesia, rigidity or orofacial dyskinesia. The homovanillic acid (HVA) concentrations of the cerebrospinal fluid at entry were comparable to those of age-matched controls. Nor did HVA levels correlate with rigidity or bradykinesia in these early AD cases. Presence of bradykinesia or rigidity at the initial evaluation predicted more severe dementia and a poor prognosis over the period of 3 years, although interaction of initial clinical severity of dementia was significant. Of 15 patients with these signs 3 (20%) died and 8 (53%) needed institutional care, while of 17 patients without these signs only 1 (6%) died and 2 (12%) were institutionalized by year 3 (p less than 0.01).
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Cognitive profile of Alzheimer patients with extrapyramidal signs: a longitudinal study.
The cognitive profile of Alzheimer patients without (ADE-, n = 17) and with (AD, E+, n = 15) extrapyramidal signs (rigidity or bradykinesia), at the time of diagnosis, was examined in a 3-year follow-up study and compared to cognitive performance of demented (PD D+, n = 18) and nondemented (PD D-, n = 17) patients with Parkinson's disease and normal elderly controls (n = 19). Although the AD E+ and AD E- groups did not differ significantly at the initial testing, the AD E+ patients showed greater deterioration on visual, praxic and expressive speech functions as well as in category memory. The cognitive profile of the AD E+ patients was similar to that of the PD D+ patients except that the AD E+ patients recognized more false positive targets on list-learning task. The AD E- patients had better preserved praxic functions and WAIS Performance IQ but they, like AD E+ patients, recognized more false positive targets on list-learning than the PD D+ patients did. The results suggest that AD patients with extrapyramidal signs, even if mild, at the time of diagnosis may have greater progression of cognitive impairment, especially on cortical functions, which may explain earlier need for institutional care observed in previous studies as compared to patients without these signs.
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Slowing of electroencephalogram and choline acetyltransferase activity in post mortem frontal cortex in definite Alzheimer's disease.
Twenty-five (96%) of 26 patients with histologically verified moderate to severe Alzheimer's disease had abnormal electroencephalograms. The patients with the slowest (5-6 Hz) dominant occipital rhythms had significantly lower choline acetyltransferase activity in the post mortem frontal cortex than the patients with highest rhythm (8-9 Hz) (analysis of covariance adjusted for the neuropsychological test score). Concentrations of dopamine, noradrenaline or serotonin in the frontal cortex did not differ in the patient groups with the slowest and highest rhythms. Neither did scores of senile plaques or neurofibrillary tangles differ between these groups. In Alzheimer patients, the frequency of the dominant occipital rhythm correlated with the total score of the neuropsychological test (r = 0.58, P less than 0.01) and with the subscales of praxic functions and expressive speech, memory and general reasoning. The results suggest that the cholinergic deficit may contribute to the slowing of the electroencephalogram found in patients with Alzheimer's disease.
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Memory and attention in newly diagnosed epileptic seizure disorder.
Interictal disturbances of memory and attention were evaluated in 74 adults with newly-diagnosed untreated epileptic seizures and no other known brain pathology. In approximately 30% of the patients with cryptogenic seizures, the average memory and attention scores indicated subtle dysfunction compared with normal control group. The patients had difficulties in tasks requiring memory, sustained attention and flexible mental processing, whereas they had normal attention span, simple speed of tracking and simple psychomotor speed. The memory difficulties may be related to attentional dysfunction leading to impaired or slowed initial encoding of memory trace, and also to a deficit in storing process and hippocampal dysfunction. These findings could have important implications for establishing criteria for identifying patients who develop chronic epilepsy and who thereby would benefit from early therapeutic intervention.
Adolescent↗
Aging and spectral analysis of EEG in normal subjects: a link to memory and CSF AChE.
We studied the effect of aging on EEG spectra recorded from T5-O1 (T6-O2) derivation. The aging series composed of 52 normal individuals aged 20 to 91 years. Seventy-nine per cent of visual and 81% of quantitative EEGs were considered normal. The absolute amplitude of delta and theta bands and absolute power of delta band were lower for the oldest group (aged 60 and over) than for the youngest group (aged 20-39 years). Age was inversely related to the amount of delta and theta indicating that the amount of slow activity in quantitative EEG does not increase with age in the context of good health status. Women had more beta activity compared with men. In addition, the amount of beta and alpha bands showed tendency for a reduction with age. Fifteen subjects aged 50 years or older participated in a 2-year follow-up including EEG and neuropsychological evaluation. Seven of them deteriorated in learning ability and showed increase in delta activity. In the oldest age group, delta amplitude was positively correlated with intrusion errors in the list learning test and inversely related to acetylcholinesterase activity of the CSF. Thus, a link between the cholinergic system, EEG slowing and memory problems in old age is suggested.
Acetylcholinesterase↗
Somatostatin and cognitive functions in Alzheimer's disease--the relationship of cerebrospinal fluid somatostatin increase with clinical response to tetrahydroaminoacridine.
We studied the effect of tetrahydroaminoacridine (THA) on cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI) in probable Alzheimer disease (AD) patients (n = 20) who took part in an open THA treatment trial. The maintenance dose (100 mg/day) was continued for 4 weeks. Samples of CSF were obtained before treatment and at the end of the treatment period. The CSF-SLI increased significantly (P = 0.01) in the responders for the treatment (increase of the Mini-Mental State Examination score greater than or equal to 3; n = 11), while the non-responders (n = 9) showed a significant decrease of CSF-SLI (P = 0.003). The change of CSF-SLI had also a significant correlation (P = 0.001) with neuropsychological performance. We conclude that the effects of of THA on the CSF-SLI may be due to presynaptic cholinergic or direct somatostatinergic stimulation.
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Serial EEG in Alzheimer's disease: 3 year follow-up and clinical outcome.
We describe EEG findings and clinical outcomes of 24 Alzheimer (AD) patients over a 3 year follow-up period. Three records, baseline, 1 year and 3 year, were available for 13 patients. Although the majority of the patients showed slowing of the EEG over 3 years, evolutions of the EEG changes were not equal in all patients. In 12 (50%) of the patients the EEG from T6-O2 derivation was normal or slightly abnormal in the initial record and remained stable during 1 year. At year 3, only 2 patients still had normal EEGs and mild dementia, probably representing a subgroup of AD with a benign course, 7 patients needed institutional care and 3 had died. EEG slowing at the time of diagnosis was predictive of poor outcome at year 3; absolute theta amplitude was the best discriminating variable of outcome. The results support the idea of heterogeneity of AD patients and suggest that EEG may provide valuable information for prediction of outcome.
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Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease.
Cortical functions and slow-wave activity in the spectral analysis of the electroencephalogram (EEG) have been studied in 19 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease with dementia (PD), and 14 control subjects (C) to determine which functions are explained by their relationship of slow-wave activity. Multiple regression analyses revealed that a variance in visual functions, praxia of the hand, automatic speech, speech understanding, and retrieval from semantic memory were explained by their relationship with slow-wave activity in EEG in the AD group but not in the PD or C groups. The PD and AD groups exhibited equal cortical dysfunctions and mean amplitudes of delta activity in EEG. The cholinergic system, disrupted in AD, has been shown to be important in the regulation of neocortical electrical activity and may be associated with the processing of cortical functions.
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Different patterns of cognitive decline related to normal or deteriorating EEG in a 3-year follow-up study of patients with Alzheimer's disease.
To determine if the pattern of cognitive decline in Alzheimer's disease (AD) patients with normal EEG differs from that in patients with abnormal EEG at the early stage of the disease, we have followed 12 AD patients with normal EEG (NEEG) and 12 patients with deteriorating EEG (DEEG). The AD patients with DEEG showed a decline of praxic functions, confrontation naming, and automatic speech functions. In contrast, the AD patients with NEEG did not show a deterioration of these functions during the 3-year follow-up period. Visual functions, understanding of speech, and memory functions deteriorated similarly in both groups. The clinical severity of dementia increased in both groups. Patients with DEEG showed a tendency toward a higher frequency of extrapyramidal symptoms and a higher risk of institutionalization than the patients with NEEG. Thus, an abnormal EEG at the early stage of AD may predict a more severe decline in cognitive functions.
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Longitudinal EEG spectral analysis in early stage of Alzheimer's disease.
Twenty-four patients with mild to moderate Alzheimer's disease (AD) were studied using quantitative spectral analysis of EEG at the time of the diagnosis and 1 year later. In 50% of the patients EEG spectra from the T6-O2 derivation were either normal or mildly abnormal at baseline and did not change at 1 year. In another half of the patients the mean quantitative EEG variables (the alpha and the delta power and the mean frequency) deteriorated significantly when baseline and 1 year values were compared. The patient groups with deteriorating and stable EEGs did not differ in age, sex, age at onset or duration of the disease or clinical severity at baseline or at 1 year. Dementia also progressed significantly in both subgroups of AD patients. We conclude that even if the mean values of quantitative EEG variables analysed from the T6-O2 derivation showed distinct slowing at the time of the AD diagnosis and further deterioration 1 year later, in 50% of these early AD cases there was no EEG alteration or worsening in 1 year follow-up, suggesting heterogeneity of the disease.
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Different error pattern of episodic and semantic memory in Alzheimer's disease and Parkinson's disease with dementia.
To evaluate the possible differences in memory dysfunction we analysed the episodic and semantic memory of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) with dementia, and age-matched normal controls (NC). The memory was examined with story recall tests, list learning test with Buschke selective reminding method and category naming test. Both AD and PD groups committed more prior-story intrusion errors as compared with the NC subjects, but only the AD patients committed more extra-story intrusion errors. Both patient groups committed more extra-list intrusion errors than the NC group. Furthermore, the AD patients made more extra-list intrusion errors and recognized more false positive targets than the PD patients did. The results suggest that AD and PD patients have different patterns of memory dysfunction. The AD patients seem to perform poorly because of their inability to inhibit irrelevant information and because of increased sensitivity to interference, whereas the deficits of PD patients only reflect sensitivity to proactive interference.
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Vasopressin levels in CSF of Alzheimer patients: correlations with monoamine metabolites and neuropsychological test performance.
Concentrations of vasopressin (AVP) and monoamine metabolites (HVA, 5-HIAA, MHPG) in cerebrospinal fluid (CSF) were measured and compared with memory functions in patients with dementia of Alzheimer type (DAT) and control subjects. CSF concentrations did not differ between the DAT patients and the controls, or between patients with different degrees of dementia. There were no correlations between concentrations of vasopressin and monoamine metabolites in CSF or between the CSF measures and psychological test scores, except for a correlation between CSF HVA and immediate and delayed story recall. These data suggest that probable damage to the vasopressinergic and monoaminergic systems in DAT is not reflected in the CSF of patients in early stages of the disease, nor is a deficit in these systems or their interaction the primary cause of cognitive impairment in DAT.
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Cerebrospinal fluid somatostatin correlates with spectral EEG variables and with parietotemporal cognitive dysfunction in Alzheimer patients.
Somatostatin levels of the cerebrospinal fluid (CSF) were correlated with variables of quantitative EEG and with neuropsychological performance in patients with probable Alzheimer's disease. Low somatostatin levels of CSF correlated with decreased beta activity and with decreased mean frequency in the combined alpha and theta EEG range. In the subgroup of mild Alzheimer cases CSF somatostatin correlated positively also with alpha power, and the peak and the mean frequency, and negatively with theta power but not with delta activity. Furthermore, low somatostatin of the CSF correlated with neuropsychological tests assessing temporoparietal dysfunction. To our knowledge, this is the first study to indicate the correlation between spectral analysis results of the EEG and CSF somatostatin suggesting that the relationship between somatostatin and EEG variables is worthy of further studies.
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Recall and recognition memory in patients with Alzheimer's and Parkinson's diseases.
Alzheimer's and Parkinson's diseases are associated with cognitive impairment, although the pattern of cognitive dysfunction is not identical. We investigated the recall and recognition memory of 18 patients with idiopathic Parkinson's disease (PD) and of 32 patients with probable Alzheimer's disease (AD). In the list-learning test using Buschke's selective reminding method, PD patients showed superior delayed recognition memory capability compared to AD patients, whereas immediate recall did not differ in the two groups. In the delayed story recall, PD patients were also able to benefit from rehearsal and probe more than AD patients. The results suggest that PD patients are able to bind information better into long-term storage than are AD patients. This may be due to better function in PD of the entorhinal cortex and hippocampus.
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Cholinergic deficit in Alzheimer's disease: a study based on CSF and autopsy data.
Cholinesterase (ChE) activity was measured as a possible marker of cholinergic neurotransmission of the brain in CSF of 93 patients with probable Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and of 29 control patients. ChE activity in CSF was decreased significantly in the AD/SDAT patients as compared to the controls. This reduction correlated significantly with the various measures of the severity of dementia. However, the reduction of ChE activity was only moderate (25-30%) even in patients with the most severe dementia and nonsignificant in patients with early symptoms of AD/SDAT. The significance of various confounding factors, which may interfere with CSF ChE measurements is discussed. Our findings seem to indicate that the deficiency of cholinergic neurons is not directly reflected in CSF and that the measurements of ChE activities in CSF are not helpful in diagnosing AD/SDAT. In the autopsy study the activities of cholineacetyltransferase (ChAT) and ChE were determined for ten brain areas of 20 AD/SDAT patients and of 14 controls. In AD/SDAT patients ChAT activity was profoundly decreased (50-85% decrease) in the cortical areas and hippocampus, but was unchanged or only mildly reduced in other subcortical brain areas. This study further confirms that the affection of cholinergic neurons is limited to projections from nucleus basalis to cortex and hippocampus, whereas other cholinergic neurons, like in striatum, seem to be relatively spared. In general, the activities of ChAT and ChE were lower in Alzheimer patients dying at younger age suggesting more severe disease process with these patients.
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Acetyl- and butyrylcholinesterase activity in the cerebrospinal fluid of patients with Parkinson's disease.
In this study we investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities and the molecular forms of these enzymes in the cerebrospinal fluid (CSF) of non-demented and demented Parkinsonian patients and in controls. The ratio of AChE to BChE activity was lower in the CSF of demented patients than in non-demented patients, although AChE and BChE activities and the molecular forms of AChE and BChE were the same in the different groups of patients. AChE activity in CSF did not vary according to the severity or duration of dementia associated with Parkinson's disease or with the disability stage of Parkinson's disease. BChE activity in CSF correlated with these clinical parameters, and patients with cerebral atrophy had higher BChE activity in CSF than those patients without atrophy. These alterations in the BChE activity of CSF may be related to gliosis which occurs in the degenerating brain tissue.
Acetylcholinesterase↗