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M Hallikainen

Publications and source records attributed to M Hallikainen.

28 records · Page 2Linked to original sources

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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Habituation of auditory N100 correlates with amygdaloid volumes and frontal functions in age-associated memory impairment.

We studied the habituation of auditory N100 responses in subjects with age-associated memory impairment (AAMI) and in healthy age-matched volunteers. The findings were correlated with volumes of the amygdala, hippocampus, and frontal lobe measured by magnetic resonance imaging (MRI), as well as with subjects' performance on tests assessing frontal lobe functions and memory. Habituation of N100 did not differ across AAMI subjects and controls. However, in AAMI subjects there was a significant correlation between habituation of N100 and volumes of the amygdala; the more reduced habituation, the smaller volume. In addition, decline in habituation of N100 correlated with impaired performance on a visual memory test (Heaton Visual memory test (Heaton Visual Retention Test; r = 0.77; p < 0.001) and impairment on tests assessing frontal functions (Verbal Fluency, Trail Making Test, and Stroop). Habituation of N100 was not related to age or sex. To our knowledge this is the first study to demonstrate a relationship between habituation of evoked responses, MRI volumetric measures, and performance on psychometric tests. The results suggest that impaired memory and frontal lobe functions in AAMI subjects may be associated with poor habituation of N100. Since habituation reflects focusing of attention to relevant features of stimuli, impairment of this mechanism and subsequent defective memory trace formation may contribute to the observed deficits on memory tests.

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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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The interuncal distance in Alzheimer disease and age-associated memory impairment.

PURPOSE: To examine the value of measurement of the interuncal distance in the diagnosis of mild to moderate Alzheimer disease. METHODS: We measured interuncal distance from coronal MR scans acquired on a 1.5-T imager. We estimated interuncal distance from a total of 141 subjects: 54 patients diagnosed according to the National Institute of Neurological and Communicative Disorders and the Alzheimer's Disease and Related Disorders Association criteria of probable Alzheimer disease, 40 subjects fulfilling the National Institute of Mental Health criteria of age-associated memory impairment, 27 healthy cognitively normal older control subjects, and 20 control subjects younger than 50 years of age. For comparison we normalized interuncal distance for a horizontal line drawn through the inner cranium at the level of the uncus (interuncal distance/intracranial width ratio), for the brain area (interuncal distance/brain area) and for the intracranial area (interuncal distance/intracranial area). RESULTS: The standard interuncal distance and the interuncal distance/intracranial width differed between the young control subjects and the other groups, but did not differ among the control, age-associated memory impairment, and Alzheimer disease groups. The Alzheimer disease group had significantly greater interuncal distance/intracranial area and interuncal distance/brain area compared with age-matched controls. A considerable overlap was found, however, in the values of patients with Alzheimer disease and control subjects. The cutoff point of 30 mm for interuncal distance yielded 37% sensitivity and 72% specificity to distinguish patients with Alzheimer disease from nondemented elderly subjects. Interuncal distance was not significantly related to the clinical severity of Alzheimer disease as assessed by Clinical Dementia Rating Scale and Mini-Mental Status Examination. Instead, there was a strong correlation between standard and normalized interuncal distance and age in the whole study population and in nondemented subjects. CONCLUSIONS: Our results showed that in a series of 54 patients with mild to moderate Alzheimer disease, interuncal distance was not a reliable diagnostic tool. The study also confirmed the strong age dependence for interuncal distance.

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Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment: correlation to visual and verbal memory.

Age-associated memory impairment (AAMI) is a common but disputed entity. It is unclear whether AAMI is a phenomenon of normal aging or an early sign of Alzheimer's disease. The present study aimed to identify possible structural abnormalities in the medial temporal lobe of AAMI subjects. We measured volumes of the hippocampus and amygdala by MRI in 16 AAMI subjects and in 16 age- and sex-matched controls and correlated the volumes with subjects' performance on two visual memory tasks (the Benton and the Heaton visual retention tests) and on a verbal memory task (the Buschke-Fuld Selective Reminding Test). The mean hippocampal and amygdaloid volumes normalized for brain size per se did not differ between the two study groups. In controls, but not in AAMI subjects, the right hippocampus was larger than the left. Accordingly, the volumetric asymmetry between the right and left hippocampi was smaller in AAMI subjects than in controls (Student's t test, p < 0.05). The volume of the right hippocampus (r = 0.37, n = 32, p < 0.05) and the magnitude of the asymmetry between the right and left hippocampi (r = 0.38, n = 32, p < 0.05) correlated with total score on the Benton test. We also found significant correlations between the amygdaloid volumes and the performance on visual memory tests but not with score on the verbal memory test.(ABSTRACT TRUNCATED AT 250 WORDS)

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Circulating immune complexes in sera from patients with Alzheimer's disease and subjects with age-associated memory impairment.

Before, we reported a higher frequency of circulating immune complexes (CIC) in the sera from institutionalized Alzheimer's disease (AD), multi-infarct dementia and Down's syndrome patients than from age-matched controls. In this study, we tested the presence of CIC in the sera from an extended series of hospitalized AD patients, AD patients living in the community, from age-associated memory impairment (AAMI) subjects as well as from nursing home and community controls. We used two methods to measure CIC, C1q binding Elisa (C1qB-Elisa) and conglutinin binding (KgB-Elisa). The AD patients showed the highest frequency of positive findings and differed from the controls in KgB (42% vs. 17%) (Chi-square, p = 0.01) and C1qB (30% vs. 11%) (p < 0.05). In severe AD, 14/19 patients were KgB positive and 11/19 were C1qB positive and differed from controls. The frequency of CIC for the patients with moderate or mild dementia, the AAMI subjects and controls was similar. In the multivariate linear regression analysis, high CIC values of the AD patients significantly associated with a long disease duration and a history of recurrent urinary infections but not with age, sex, hospitalization, or the Mini-Mental Status score. We conclude that AD patients with severe dementia frequently show CIC but those with mild or moderate disease do not. The CIC relate to a long disease duration and a history of recurrent urinary infections.

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Selegiline treatment and the extent of degenerative changes in brain tissue of patients with Alzheimer's disease.

BACKGROUND: A beneficial effect of selegiline (L-deprenyl) in Alzheimer's disease (AD) has been reported in several clinical studies. METHODS: The brain tissue from 17 deceased patients, members of a double-blind clinical trial to assess the potential benefit of selegiline in AD, were analysed. FINDINGS: In our study, the decrease in the Mini-Mental State Examination (MMSE) scores during the progress of the disease had been significantly influenced by selegiline treatment. Prior to death, the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo. However, according to our results, none of the lesions critical for AD diagnosis, such as counts of senile/neuritic plaques, neurofibrillary tangles or beta-A4 load, were influenced by the selegiline treatment. INTERPRETATION: In conclusion, according to our study, mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment, leading to the functional benefit found in AD.

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MR T2 relaxometry in Alzheimer's disease and age-associated memory impairment.

A prolonged MR T2 relaxation time was proposed to mark the presence and severity of Alzheimer's disease (AD). We studied the value of T2 relaxometry in diagnosing early AD. T2 was measured from 54 patients with AD, 25 subjects with age-associated memory impairment (AAMI), 18 elderly and 16 young controls. The AD patients had longer T2 in the right hippocampal head (104 +/- 11 ms) and tail (98 +/- 10 ms) than age-matched controls (95 +/- 5 and 92 +/- 9 ms, respectively). This prolongation was not related to age. In the AD group, the T2 of the left hippocampal head also correlated with the clinical severity. The T2 of the amygdala did not differ across the groups. Increased T2 in the temporal and parietal white matter and the thalamus related to increasing age rather than to the diagnostic category. The AAMI subjects had T2 comparable with those of age-matched controls. Despite the prolongation of T2 in the AD group the possible diagnostic value was compromized by a substantial overlap between the study groups. We, thus, conclude that the T2 relaxometry is not a reliable method for diagnosing early AD.

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MRI of the hippocampus in Alzheimer's disease: sensitivity, specificity, and analysis of the incorrectly classified subjects.

In this study, magnetic resonance imaging (MRI) of the hippocampus for the diagnosis of early Alzheimer's disease (AD) is evaluated. We measured hippocampal volumes and the area of the medial hippocampus with a 1.5 T MR imager in 160 subjects: 55 patients with probable AD according to the NINCDS-ADRDA criteria, 43 subjects fulfilling the NIMH criteria of age-associated memory impairment (AAMI), 42 cognitively normal elderly controls, and 20 controls younger than 50 years. Three methods for normalization were compared. The hippocampi were atrophied in the AD patients, but not in the AAMI subjects or the elderly controls. There was no significant correlation between hippocampal volumes and age in the nondemented subjects. The discrimination based on volumetry resulted in an overall correct classification of 92% of AD patients vs. nondemented elderly subjects, whereas discrimination based on hippocampal area was less accurate, producing a correct classification in 80% of the subjects. We conclude that the hippocampus as assessed by MRI volumetry is atrophied early in AD, and spared by aging or AAMI. A brief critical review of previous studies is in concordance with the presented data: all the previous studies that have used volumetry, have similarly ended up with a good classification, whereas simpler or subjective measurements, subject to various sources of bias, have produced most variable results.

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