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Biomedical subjects

E L Helkala

Publications and source records attributed to E L Helkala.

At least 37 records · Page 2Linked to original sources

Hippocampal volumes in Alzheimer's disease, Parkinson's disease with and without dementia, and in vascular dementia: An MRI study.

Hippocampal atrophy detected by volumetric MRI is a sensitive feature of early Alzheimer's disease (AD), but there are no studies evaluating hippocampal atrophy by MR volumetry in other dementing diseases. We therefore compared hippocampal volumes in a total of 113 subjects: 50 patients with mild to moderate AD, 9 patients with vascular dementia (VaD), 12 patients with idiopathic Parkinson's disease (PD) without dementia, 8 patients with PD and dementia (PDD), and 34 elderly control subjects. Thin, coronal, contiguous images were obtained by a 1.5-T MR imager. All patient groups had significantly smaller volumes of the hippocampus compared with the control group. In the PDD group, the absolute volumes were even smaller than in the AD group. In the PD group, the volumes were diminished to a lesser but significant extent. The volumes in the VaD group varied: of nine patients, two had no atrophy, three had unilateral, and four had bilateral atrophy. We postulate that hippocampal atrophy does not seem to be a specific phenomenon of dementia in AD but also occurs in VaD and PDD, and even in PD when no dementia is present. However, coexistence of AD pathology in our PD and VaD patients cannot be ruled out. Further studies with access to neuropathologic data are needed.

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Tetrahydroaminoacridine modulates technetium-99m labelled ethylene dicysteinate retention in Alzheimer's disease measured with single photon emission computed tomography imaging.

The present study investigated if acute treatment with tetrahydroaminoacridine (THA) (25 or 75 mg, p.o.) affects technetium-99m labelled ethylene dicysteinate (ECD) retention abnormalities in patients with mild to moderate Alzheimer's disease (AD; mean age 69 years). THA (75 mg) increased temporal, prefrontal and occipital ECD retention (normalized to cerebellum) in mildly demented AD patients, but 25 mg of THA had no effect on ECD retention. After 75 mg THA, prefrontal and temporal ECD retention correlated with improved executive and memory functioning, respectively. THA (25 or 75 mg) had no measurable effect on ECD retention of moderately demented patients.

Aged↗

Hippocampal atrophy, acute THA treatment and memory in Alzheimer's disease.

We designed the present study to investigate the hypothesis that progression of hippocampal pathology may decrease the therapeutic effects of anti-cholinesterase drug, tetrahydroaminoacridine, on memory functioning in Alzheimer's disease (AD) patients. Memory, visuoconstructive, executive and vigilance functions were assessed after administration of placebo (p.o.; two placebo sessions) and tetrahydroaminoacridine (one session for 25 and 75 mg, p.o.). Eight patients performed better on list learning test during tetrahydroaminoacridine 75 mg than after placebo or tetrahydroaminoacridine 25 mg. The responders performed during baseline examination better than the non-responders in executive and some declarative memory functions, and had higher MMSE scores than the non-responders. The responders had larger left and right hippocampi than the non-responders. The hippocampal volume correlated with list learning performance. The results suggest that severe hippocampal atrophy may block memory improving effect of an anticholinesterase drug, tetrahydroaminoacridine.

Alzheimer Disease↗

The association of apolipoprotein E polymorphism with memory: a population based study.

Several studies have shown an association between the apolipoprotein epsilon 4 allele and Alzheimer's disease (AD). The allele epsilon 2 has been associated with survival and longevity. We wanted to examine whether the relationship between cognitive efficiency and apolipoprotein E polymorphism (APOE) exists in a random sample of 916 non-demented elderly subjects. Episodic memory was examined with the list learning test, and with immediate and delayed recall of the figures. Semantic memory was examined with the Category and Verbal Fluency Tests. Constructional abilities were examined by copying the figures. Attention functions were examined with Trail Making A and B tests. We found that subjects with APOE E2/2 and 2/3 phenotypes showed better learning ability than those subjects with the APOE E2/4, 3/4 or 4/4 phenotypes. Impaired memory was not related to the excess of cardiovascular diseases in the subjects with APOE E2/4, 3/4, 4/4 phenotypes. Thus they may be associated, at least partly, with genetic factors.

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Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: correlation with memory functions.

We studied the usefulness of measuring volumes of the hippocampus, amygdala and frontal lobes with coronal magnetic resonance imaging (MRI) scans in the diagnosis of early Alzheimer's disease (AD). We examined 32 patients diagnosed according to the NINCDS-ADRDA criteria of probable AD and 16 age-matched healthy cognitively normal controls. The AD patients had mild dementia with a mean score of 22.8 in the Mini-Mental Status Examination (MMSE). We used a 1.5 T magnetic resonance imager and normalized the volumes for brain area. The AD patients had significantly smaller volumes of the right and the left hippocampus (-38%) (ANOVA, p < 0.0001) and the left frontal lobe (-16%, p < 0.05) compared to controls. The reductions in volumes of the right frontal lobe (-13%), the right amygdala (-14%) or the left amygdala (-18%) were not statistically significant. In the discriminant function analysis which included the volumes of the hippocampus, amygdala, and the frontal lobes and age, the volumes of the left and right hippocampus, the left and right frontal lobe, and the right amygdala entered the model and we could correctly classify 92% of the subjects into AD and control groups (Chi-square 42.6, df 5, p < 0.001). By using the volumes of the hippocampus, the frontal lobes or the amygdala on their alone, the correct classification was achieved in 88%, 65% and 58% of the subjects, respectively. In addition, in AD patients the volumes of the left hippocampus correlated significantly with the MMSE score and with immediate and delayed verbal memory; the smaller the volume the more impaired was their performance. Our data indicate that measurements of volumes of the hippocampus might be useful in diagnosis of early AD.

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Regional cerebral blood flow measured by 99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxic, and executive functions. The rCBF measured by 99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N = 12) and AD2 (N = 23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.

Aged↗

Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes.

An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-beta-protein and tau protein in vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (-54% of control) and the right amygdala (-37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia.

OBJECTIVE: To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period of more than 3 years. DESIGN: Prospective cohort study. SETTING: The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland. PARTICIPANTS: A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI. MEASUREMENTS: A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group. RESULTS: Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests. CONCLUSION: The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.

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Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland.

Aging has multiple effects on memory in normal subjects. However, information on the prevalence of age-associated memory impairment (AAMI) is scanty. We studied the prevalence of AAMI in a randomly selected population of 1,049 subjects aged 60 to 78 years from eastern Finland. Research criteria proposed by the National Institute of Mental Health (NIMH) Work Group were applied. We calculated prevalence rates for AAMI by the inclusion criteria alone (subjective and objective memory impairment and no dementia) as well as by the inclusion and exclusion criteria (evidence of any neurologic or other medical disorder that could produce cognitive deterioration) for the total study population, for both sexes, and for four age groups (60 to 64, 65 to 69, 70 to 74, and 75 to 78 years). Subjective memory impairment was present in 76.3% of the subjects. Prevalence rates for objective memory impairment ranged from 31.9 to 78.4% in individual tests. A total of 564 subjects (239 men, 325 women) were classified as having AAMI by the inclusion criteria alone, giving a prevalence rate of 53.8% (men, 57.4%; women, 51.3%). When we included the exclusion criteria, the prevalence of AAMI decreased to 38.4% (men, 42.5%; women, 35.7%). By both methods, age- and sex-specific prevalence rates were highest in the youngest group, aged 60 to 64 years, and lowest in the oldest group, aged 75 to 78 years. We conclude that the prevalence of AAMI, by the diagnostic criteria of the NIMH Work Group, is high in the elderly Finnish population.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Short-term and long-term memory in elderly patients with NIDDM.

OBJECTIVE: To determine cognitive and memory dysfunction associated with non-insulin-dependent diabetes mellitus (NIDDM) and its relationship with depression, metabolic control, and serum lipids. RESEARCH DESIGN AND METHODS: We studied a well-characterized group of 20 elderly patients with NIDDM and 22 control subjects with normal glucose tolerance recruited from a larger population-based sample. In addition to clinical and laboratory examinations, self-rating questionnaires that assess minor psychiatric disorder (General Health Questionnaire) and depression (Zung scale) were completed by patients and control subjects. Memory was examined with digit and block-span tests, word-list learning, Heaton Visual Memory Test, and Moss Visual Span Test. Executive functions were examined by Trail-Making A and B test and by Verbal and Category Fluency Tests. Visuoconstructive reasoning was examined with the block design subtest of the Wechsler Adult Intelligence Scale. RESULTS: The NIDDM patients showed preserved memory span, but poor performance in learning tasks compared with control subjects. The patients recalled no fewer words than the control subjects, but the process of of learning seemed to be different in the two groups. The recognition of the learned words was not impaired. Elevated serum total and very-low-density lipoprotein triglyceride levels, measured either before examinations or 5 or 10 years earlier, were associated with effects on retrieval from semantic memory in NIDDM patients. CONCLUSIONS: The NIDDM patients had impaired control of their learning processes. Elevated serum triglyceride levels may be related to control of mental processing in diabetic patients.

Adult↗

Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study.

OBJECTIVE: To determine the association between the e4 allele of apolipoprotein E and Alzheimer's disease in a randomly selected population sample. DESIGN: Cross sectional population based study. SUBJECTS: 980 people aged 69 to 78 (349 men, 631 women). SETTING: Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES: Presence of e4 allele and diagnosis of Alzheimer's disease by detailed neurological and neurophysiological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer's disease. The frequency of the apolipoprotein E e4 allele was 0.359 in patients with Alzheimer's disease and 0.165 subjects without dementia (P < 0.0001). The prevalence of Alzheimer's disease was 2.9% in subjects with no e4 alleles, 7.6% in subjects with one e4 allele, and 21.4% in subjects with two e4 alleles of apolipoprotein E. CONCLUSIONS: Allele e4 of apolipoprotein is associated with Alzheimer's disease in a dose-response fashion in a randomly selected elderly population.

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Subjective memory complaints and personality traits in normal elderly subjects.

OBJECTIVE: To evaluate the relationship between objectively measured memory functions and subjective complaints of memory disturbance and whether subjective complaints are affected by some personality traits or affective states. DESIGN: Cross-sectional two-group comparison. SETTING: The city of Kuopio in Eastern Finland, considered representative of the urban elderly population of Finland. PARTICIPANTS: Originally 403 subjects aged 67-78 years from the random sample and then two matched study groups initially including eighteen subjects but only ten in the final analysis. MEASUREMENTS: Screening and follow-up examinations of subjects with and without subjective memory complaints: (1) Memory functions: Benton's visual retention test and the paired-associated learning subtest of Wechsler Memory Scale. (2) Memory complaints: Memory Complaint Questionnaire. (3) Personality traits and affective state: Two subscales from Minnesota Multiphasic Personality Inventory and Geriatric Depression Scale. RESULTS: Complaints of memory loss did not correlate with the actual memory performance in the tests. However, those subjects who most emphatically complained of memory disturbance had greater tendencies toward somatic complaining, higher feelings of anxiety about their physical health, and more negative feelings of their own competence and capabilities than those who did not complain of memory deterioration associated with aging. CONCLUSIONS: The study suggests that subjective feelings of memory impairment are more closely associated with personality traits than with actual memory performance in normal elderly people.

Affect↗

Electrophysiological and neuropsychological effects of a central alpha 2-antagonist atipamezole in healthy volunteers.

We studied the electrophysiological and neuropsychological effects of acute modulation of central noradrenergic (NA) transmission using a specific alpha 2-antagonist atipamezole (ATI) in sic healthy volunteers. ATI had effects on resting EEG, auditory event-related potentials and neuropsychological tests. Quantitative EEG revealed increased total power in frontal, parietal and temporo-occipital areas without significant changes in the mean or peak frequencies. Event-related potentials showed no effects on the active attention-related processing negativity or the passive mismatch negativity, but frontally recorded mean amplitude of target-P300 was decreased. Neuropsychological tests after ATI revealed improvement in Digit Span, more errors in Word Recognition task, and no effects on Moss spatial recognition task. In healthy subjects with intact NA systems and without any attention deficit, ATI produced evident NA overactivity. ATI decreased the spontaneous thalamocortical oscillation of EEG and improved focused attention (Digit Span). It impaired, however, more divided attention (decreased mean P300 amplitude, increased errors in Word Recognition).

Adrenergic alpha-Antagonists↗

The relationship of cerebrospinal fluid monoamine metabolites with clinical response to tetrahydroaminoacridine in patients with Alzheimer's disease.

The effect of tetrahydroaminoacridine (THA) on the cerebrospinal fluid (CSF) monoamine metabolites was studied in 22 patients with Alzheimer's disease in an open treatment trial. The CSF monoamine metabolites were assayed at baseline and after 4 weeks' active THA treatment with 100 mg/d. A statistically significant increase in the CSF homovanillic acid (HVA) and in 5-hydroxyindoleacetic acid (5-HIAA) content was found. The increase of the CSF 5-HIAA level correlated significantly with improvement in cognitive tests and in the Instrumental Activities of Daily Living Scale. We conclude that besides its anticholinesterase activity THA enhances also the monoaminergic neurotransmission in the brain and that the clinical improvement during THA treatment may be partly mediated through the monoaminergic system.

Activities of Daily Living↗

Cognitive and memory deficits in untreated Parkinson's disease and amyotrophic lateral sclerosis patients: a comparative study.

We investigated the profile of cognitive and memory deficits of 22 Parkinson's disease (PD), 24 amyotrophic lateral sclerosis (ALS) patients and 26 age-matched controls. The patients were at the early phase of the disease and untreated. The ALS patients exhibited deficits in simple visuoperceptual functions and in complex visuoperceptual reasoning (Digit Symbol and Block Design tests), whereas the PD patients showed deficits only in simple visuoperceptual functions. Moreover, both ALS and PD patients had impairment in tasks requiring set shifting from one reaction to another that may suggest frontal lobe dysfunction. The ALS and PD patients also showed impairment in the task of learning a word list with effort-demanding organization of the material to be remembered. However, preserved delayed recall of logical passages suggests that memory, per se, is not impaired in ALS or in PD. The patterns of errors in a test of recognition of learned words imply, at least partially, different underlying deficits in the two diseases. An inability to inhibit irrelevant information may contribute to memory impairment in ALS patients, whereas the memory deficit in PD may derive from lowered motivation or initiating behaviour.

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Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease.

Adult↗

Wide third ventricle correlates with low choline acetyltransferase activity of the neocortex in Alzheimer patients.

We evaluated central, temporal, and cortical atrophy by linear measurements on brain computed tomography (CT) in 17 patients with moderate to severe histologically verified Alzheimer disease (AD) compared with findings in 84 nondemented elderly controls. Measurements were adjusted for age and head size. The AD patients had wider third and lateral ventricles as well as larger temporal horns and Sylvian fissures compared with controls. Cortical atrophy tended also to be more pronounced for AD patients relative to controls. Thus measures of central and temporal atrophy clearly distinguished AD patients from normal aged individuals. In AD patients, the width of the third ventricle was significantly correlated with the choline acetyltransferase (ChAT) activity in the post-mortem frontal cortex (r = 0.65, p = 0.005) and in the temporal cortex (r = 0.59, p = 0.006). CT measures did not correlate significantly with neurofibrillary tangle or senile plaque scores. The result suggests that the width of the third ventricle better reflects the degree of cholinergic deficit than severity of histopathological changes, scores of plaques, and tangles in AD.

Aged↗

Essential hypertension and cognitive function. The role of hyperinsulinemia.

The relation between hypertension and cognitive function is not well established. Therefore, we examined cognitive function in a random sample of 744 nondiabetic elderly inhabitants of Kuopio, East Finland. Five brief neuropsychological tests known to be sensitive to cognitive impairment due to dementia--the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT), the Buschke Selective Reminding Test (BSR), Russell's Adaptation of the Visual Reproduction Test (HVR), and the Verbal Fluency Test (VFT)--were used to evaluate cognitive function. The performance of the hypertensive group (n = 378) was impaired in almost all test items compared with that of the normotensive group (n = 366), but the difference between these two groups was statistically significant in 5 of 19 test items only. Moreover, within the hypertensive group, hyperinsulinemic (fasting plasma insulin > 17.9 mU/L) hypertensive subjects (n = 57) scored worse than normoinsulinemic hypertensive subjects (n = 321) in 16 of 19 test items and worse than the normotensive subjects in the same 16 of 19 test items. The difference between the hyperinsulinemic hypertensive and normotensive groups was significant in 11 test items that reflected complex cognitive function such as calculation, language, semantic memory, and problem solving. This difference in neuropsychological tests among the three study groups (normotensive, normoinsulinemic hypertensive, and hyperinsulinemic hypertensive subjects) persisted after adjustment for fasting plasma glucose, age, sex, and education in 3 test items measuring calculation, copying, and semantic memory. Thus, essential hypertension in the elderly is associated with an impairment in complex cognitive function.(ABSTRACT TRUNCATED AT 250 WORDS)

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