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Biomedical subjects

E L Helkala

Publications and source records attributed to E L Helkala.

At least 19 recordsLinked to original sources

Association of metabolic syndrome with Alzheimer disease: a population-based study.

OBJECTIVE: To assess the association of metabolic syndrome (MetS) with Alzheimer disease (AD). METHODS: The authors derived subjects from a population-based study of 980 randomly selected elderly subjects. After exclusion of all non-Alzheimer dementia cases, the final study population included 959 subjects (337 men and 622 women) aged 69 to 78 years. The presence of MetS was defined according to the National Cholesterol Education Program (Adult Treatment Panel III) criteria, and the diagnosis of AD was based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Of the study subjects, 418 (43.6%) had MetS. Probable or possible AD was diagnosed in 45 subjects (4.7%). AD was more frequently detected in subjects with MetS than in subjects without MetS (7.2 vs 2.8%; p < 0.001). The prevalence of AD was higher in women with MetS vs women without the syndrome (8.3 vs 1.9%; p < 0.001), but in men with MetS, the prevalence of AD was not increased (3.8 vs 3.9%; p = 0.994). In univariate logistic regression analysis, MetS was significantly associated with AD (odds ratio [OR] 2.71; 95% CI 1.44 to 5.10). In multivariate logistic regression analysis including also apolipoprotein E4 phenotype, education, age, and total cholesterol, MetS was significantly associated with AD (OR 2.46; 95% CI 1.27 to 4.78). If only nondiabetic subjects were included in the multivariate analysis, MetS was still significantly associated with AD (OR 3.26; 95% CI 1.45 to 7.27). CONCLUSION: Metabolic syndrome is associated with Alzheimer disease in elderly subjects.

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Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.

OBJECTIVE: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer's Disease Research Center. BACKGROUND: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. RESULTS: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (> or =6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. CONCLUSION: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

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Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study.

OBJECTIVE: To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer's disease in later life. DESIGN: Prospective, population based study. SETTING: Populations of Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Participants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998. MAIN OUTCOME MEASURES: Midlife blood pressure and cholesterol concentrations and development of Alzheimer's disease in later life. RESULTS: People with raised systolic blood pressure (>/=160 mm Hg) or high serum cholesterol concentration (>/=6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer's disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer's disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer's disease. CONCLUSION: Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer's disease in later life.

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APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

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Associations between apolipoprotein E phenotype, glucose metabolism and cognitive function in men. An explorative study in a population sample.

AIMS: To investigate the associations of the apolipoprotein E phenotype (apoE) and disturbed glucose metabolism with cognitive function in a random population sample. METHODS: A cross-sectional study was conducted, in which 528 men aged 54 or 60 years were recruited randomly from a larger population-based sample of 1516 men. A subject was defined as having abnormal glucose tolerance (AGT), if he had a clinical diagnosis of diabetes, with either dietary or oral antidiabetic treatment or showed impaired glucose tolerance in an oral glucose tolerance test. The subjects were divided into three groups according to apolipoprotein E phenotypes: (a) E2/4, E3/4 or E4/4 (apoE E4); (b) E 3/3 (apoE E3); and (c) E2/2 or E2/3 (apoE E2). Memory function was examined using a word-list learning with Buschke's selective reminding method and test. Executive functions were assessed with the Trail Making Test A and B. RESULTS: Those subjects with apoE E2 and abnormal glucose metabolism demonstrated the worst cognitive executive control compared to other groups. Simple cognitive speed did not differ between the groups. CONCLUSIONS: The exploratory analyses revealed that subjects with apoE E2 allele and AGT had worse glycaemic control and cognitive executive control compared to other groups. Different apolipoprotein phenotypes together with impaired glucose tolerance may have different cumulative adverse effects on age-related cognitive performance. Some subgroups of subjects may be especially vulnerable to cognitive impairment.

Apolipoprotein E3↗

Childhood socioeconomic position and cognitive function in adulthood.

BACKGROUND: Risk of dementia and Alzheimer's disease is higher among adults with limited education, and the less educated perform poorer on cognitive function tests. This study determines whether the socioeconomic environment experienced during childhood has an impact on cognitive functioning in middle age. METHODS: A population-based study of eastern Finnish men (n = 496) aged 58 and 64 for whom there were data on parent's socioeconomic position (SEP), their own education level, and performance on neuropsychological tests. Cognitive function was measured using the Trail Making Test, the Selective Reminding Test, the Verbal Fluency Test, the Visual Reproduction Test, and the Mini Mental State Exam. RESULTS: We found a significant and graded association between parental SEP (combined as an index) and cognitive function both prior to and after adjustment for respondent's education. Those from more disadvantaged backgrounds exhibited the poorest performance. When the separate components of the parental SEP measure were used, father's occupation and mother's education were independently associated with the respondent's score for three and five of the tests, respectively (there was no association with father's education and mother's occupation). After adjustment for the respondent's education, father's occupation was no longer associated with respondent's test score, however, the results were essentially unchanged for mother's education. CONCLUSIONS: Higher SEP during childhood and greater educational attainment are both associated with cognitive function in adulthood, with mothers and fathers each contributing to their offspring's formative cognitive development and later life cognitive ability (albeit in different ways). Improvements in both parental socioeconomic circumstances and the educational attainment of their offspring could possibly enhance cognitive function and decrease risk of dementia later in life.

Adult↗

Type-2 diabetes and cognitive function in a non-demented population.

OBJECTIVES: To study if type-2 (non-insulin-dependent) diabetes mellitus (NIDDM) is associated with cognitive dysfunction independently of clinically diagnosed dementia in an elderly population. MATERIAL AND METHODS: Cognitive function was investigated with a brief neuropsychological test battery in a non-demented elderly population consisting of 183 NIDDM (World Health Organization, 1985) patients and 732 non-diabetic subjects. RESULTS: Patients with NIDDM were impaired in the Trail-Making Test parts A and C, which may be a reflection of mildly affected frontal lobe/executive functions. Women with NIDDM performed better than non-diabetic subjects in the Mini-Mental State Examination. CONCLUSIONS: We conclude that NIDDM per se is not associated with impaired memory in the elderly, and the minor defects observed in tests of frontal lobe/executive functions are unlikely to affect daily living. In the non-demented population aged 69 78 years, NIDDM does not carry a significant risk of cognitive dysfunction, when compared to the non-diabetic subjects.

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Tetrahydroaminoacridine improves the recency effect in Alzheimer's disease.

We investigated the effects of a single administration of tetrahydroaminoacridine (25 and 50 mg, orally), a cholinesterase inhibitor, on memory function in Alzheimer's disease patients. The recall of memory items from the end of the word list (recency effect) was improved in a subgroup of Alzheimer's disease patients (responders 10 out of 28) by tetrahydroaminoacridine 50 mg. However, tetrahydroaminoacridine 50 mg had no effect on the recall of those words from the beginning or middle of the list. Tetrahydroaminoacridine did not markedly improve non-verbal delayed matching to sample or paired associates learning in any of the Alzheimer's disease patients. The "responders" performed better than the "non-responders" in tests measuring memory and frontal functions. The responders had less severe hippocampal atrophy and less prefrontal blood flow defect, and had a lower frequency of the apolipoprotein E4 allele than the "non-responders". These results suggest that acute tetrahydroaminoacridine treatment may stimulate the recency effect, and that a severe dysfunction of hippocampus and prefrontal regions blocks this effect of tetrahydroaminoacridine on short-term memory performance.

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Cognitive function in an elderly population with persistent impaired glucose tolerance.

OBJECTIVE: To study cognitive function in an elderly population with persistent impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Fasting and postload 2-h plasma glucose and insulin levels were determined at baseline in a population-based sample of 1,300 people and repeated an average of 3.5 years later in 980 subjects. At follow-up, cognitive function was evaluated in subjects with persistent normal glucose tolerance (NGT; n = 506) and IGT (n = 80) with a brief neuropsychological test battery. RESULTS: Subjects with persistent IGT scored lower in the Mini-Mental State Examination (MMSE) and in the Buschke Selective Reminding Test long-term memory scores. Multiple linear regression analysis revealed that age, education, and insulin levels (either fasting or 2-h value) were associated with the MMSE score in subjects with persistent IGT. Other potential risk factors for impaired cognitive function were not significantly associated with the MMSE score. CONCLUSIONS: Our study showed that persistent IGT in the elderly is associated with mildly impaired cognitive function, and hyperinsulinemia may account for this association.

Age Factors↗

Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study.

OBJECTIVE: To determine the association between features of the insulin resistance syndrome and Alzheimer's disease. 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 features of the insulin resistance syndrome and diagnosis of Alzheimer's disease by detailed neurological and neuropsychological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer's disease. In univariate analyses, apolipoprotein E4 phenotype (odds ratio; 95% confidence interval 3.24: 1.77 to 5.92), age (1.16; 1.05 to 1.29), low level of education (0.82; 0.72 to 0.93), low total cholesterol concentration (0.77; 0.59 to 1.00), high systolic blood pressure (1.01; 1.00 to 1.03), high fasting and 2 hour plasma glucose concentrations (1.11; 1.01 to 1.23 and 1.08; 1.03 to 1.13, respectively), high fasting and 2 hour insulin concentrations (1.05; 1.02 to 1.08 and 1.003; 1.00 to 1.01, respectively), and abnormal glucose tolerance (1.86; 1.23 to 2.80) were significantly associated with Alzheimer's disease. In multivariate analysis including apolipoprotein E4 phenotype, age, education, systolic blood pressure, total cholesterol concentration, fasting glucose concentration, and insulin concentration, apolipoprotein E4 phenotype, age, education, total cholesterol, and insulin were significantly associated with Alzheimer's disease. In 532 non-diabetic subjects without the e4 allele hyperinsulinaemia was associated with an increased risk for Alzheimer's disease (prevalence of disease 7.5% v 1.4% in normoinsulinaemic subjects, P = 0.0004). In contrast, in the 228 with the e4 allele hyperinsulinaemia had no effect on the risk of disease (7.0% v 7.1%, respectively). CONCLUSION: Features of the insulin resistance syndrome are associated with Alzheimer's disease independently of apolipoprotein E4 phenotype.

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Risk for non-insulin-dependent diabetes in the normoglycaemic elderly is associated with impaired cognitive function.

We studied cognitive function in normoglycaemic elderly subjects at different risk levels for developing non-insulin-dependent diabetes mellitus (NIDDM) and in patients with NIDDM. Risk for NIDDM was considered increased if both 2 h glucose and insulin values on oral glucose tolerance testing were higher than the median in normoglycaemic subjects, and low if the respective values were lower than the median. The increased risk group showed impairment on tests of immediate and delayed memory, attention, visuomotor speed and verbal fluency. Moreover, the increased risk group did not differ from patients with NIDDM on any cognitive tests. Our results suggest that increased risk for NIDDM is associated with widely affected cognitive function in the normoglycaemic elderly, highlighting the importance of healthy living habits.

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Relationship between EEG reactivity and neuropsychological tests in vascular dementia.

17 patients with vascular dementia (VaD) representing moderate to severe stage of the disease and 11 age-matched control subjects were examined with spectral analysis of EEG and a neuropsychological test battery comprising visual, praxic, verbal and memory functions as well as Mini-Mental Status test. VaD patients did not have less activity in the alpha band than control subjects, but the alpha amplitude ratio between eyes closed (EC) and eyes open (EO) situations (EC/EO ratio) was decreased in VaD patients, compared to controls. In VaD the variables of the awake background EEG with eyes closed (amplitude of alpha, beta, theta and delta activity; mean frequency) had only a few correlations to neuropsychological test scores. However, the (EC)/(EO) alpha ratio showed significant correlations with several neuropsychological variables in the temporo-occipital and centro-parietal derivations and some of these correlations were lateralized to the left or right hemisphere. Frontal EEG derivations with less alpha activity did not reveal any correlations to neuropsychological variables. We conclude that the dynamic EC/EO alpha ratio variable may be even more sensitive in the assessment of brain dysfunction in VaD than the background EEG variables.

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Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study.

The apolipoprotein E epsilon4 allele is the most common risk factor for Alzheimer's disease (AD). The epsilon2 allele may play a protective role in AD. Our previous cross-sectional study showed that in non-demented elderly subjects the epsilon2 allele is associated with better learning ability than other alleles. We wished to investigate the influence of different apolipoprotein E (apoE) phenotypes on cognitive functions in a 3-year follow-up study starting with a random sample of 917 non demented elderly subjects. Episodic memory was examined with the List Learning Test (Buschke's selective reminding method), as well as with immediate and delayed recall of figures. Retrieval from semantic memory was assessed with the Category and Verbal Fluency tests. Constructional abilities were examined by copying figures. Attention functions were examined with the Trail Making A and B tests. A total of 632 subjects completed the 3-year follow-up study. The subjects with apoE phenotypes E2/2 or E2/3 were able to maintain their verbal learning performance, while the learning ability of the subjects with other apoE phenotypes deteriorated. We suggest that successful mental aging may be at least in part associated with genetic factors.

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Slow-wave activity in the spectral analysis of the electroencephalogram and volumes of hippocampus in subgroups of Alzheimer's disease patients.

This study examined patients who fulfilled the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association Work Group criteria for probable Alzheimer's disease (AD; n = 35) and controls for magnetic resonance imaging and psychometric data (n = 16) and for quantitative electroencephalogram data (n = 34). A cluster analysis performed on neuropsychological variables identified 2 AD subgroups: The AD1 group (n = 12) had impaired memory and executive functions but preserved verbal and visuospatial functions. The AD2 group (n = 23) had global impairment. The AD2 group had higher theta amplitude in the temporo-occipital, centroparietal, and frontal derivation and lower peak and mean frequency than the AD1 group or controls. Both AD groups had more severe memory deficits and clearly smaller hippocampal volumes than controls. This may implicate that the degree of damage in ascending activating systems differs in these subgroups, although the damage in the hippocampus is equal.

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Prevalence of ageing-associated cognitive decline in an elderly population.

Different diagnostic definitions have been proposed for use in the characterization of mild cognitive disorders associated with ageing. Previously, we reported a high (38.4%) prevalence of age-associated memory impairment (AAMI) using the National Institute of Mental Health criteria in an elderly population. Recently, a work group of the International Psychogeriatric Association proposed criteria for 'ageing-associated cognitive decline' (AACD). The objective of this study was to evaluate the prevalence of AACD in an elderly population. We examined 403 randomly selected subjects (68-78 years of age) with tests of memory, cognitive processing, attention, verbal and visuoconstructive functions and with a structured questionnaire for health status and subjective complaints of cognitive decline. In all, 26.6% of the subjects (24.4% of women, 30. 1% or men) fulfilled the AACD criteria. The prevalence was slightly related to age and education. The rate was lowest in the oldest age of 75 - 78 years (20.5%) and highest in the age of 71 -74 years (30%). Subjects with less than 4 years of education had the lowest (14.3%) and subjects with more than 6 years of education had the highest rate (29.4%) for AACD. However, the differences between these subgroups were not statistically significant. These results suggest that the prevalence of AACD is lower than that of AAMI. As AAMI tends to identify a very heterogeneous subject group, the AACD diagnosis, which takes into account age and education specific norms in its inclusion criteria, might prove superior to AAMI in differentiating a meaningful subgroup from an elderly population both for research purposes and in clinical settings.

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EEG reactivity correlates with neuropsychological test scores in Down's syndrome.

INTRODUCTION: Down's syndrome patients express a neurodegenerative disorder and mental retardation. We studied the reactivity of EEG and its correlation with neuropsychological test score in Down's syndrome. MATERIAL AND METHODS: We studied 32 patients with Down's syndrome and 31 controls for blocking of occipital EEG activity. The temporo-occipital EEG with eyes open (EO) was compared with resting EEG with eyes closed (EC), (EC/EO ratio). RESULTS: Both Down patients and controls showed significant diminution of alpha, beta and theta activity and decrease of EEG frequency with EO. However, there was a significant impairment in Down patients in the EC/EO ratio in alpha band, compared to controls. The controls had no correlation of the alpha EC/EO ratio with age or gender. The Down patients showed a significant correlation of this variable with age which is in accordance with a gradually progressing disease. They had also significant correlations of the alpha EC/EO ratio and neuropsychological test scores which indicates that this ratio may be a more general measure of cerebral or hemispherical dysfunction than a mere impairment of visual activation. Down patients also showed significant differences in resting EEG variables, compared to the controls, even if the conventional EEG showed normal or mildly slowed dominant occipital rhythm in most of the patients. The correlation analysis between resting EEG and EC/EO ratio variables pointed out that they are relatively independent, representing different factors in the regulation of EEG. CONCLUSIONS: We believe that the alpha EC/EO ratio of EEG add a new domain in the assessment of cerebral dysfunction in Down's syndrome.

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Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism.

Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease. In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (> or = 65 years), familial late-onset (FLO) (> or = 65 years), sporadic early-onset (SEO) (<65 years), and familial early-onset (FEO) (<65 years) patients and into three subgroups according to their ApoE genotype zero epsilon4, one epsilon4, and two epsilon4 alleles. The AD subgroups did not differ in the global clinical severity of dementia or the duration of the disease. SLO, FLO, SEO, and FEO subgroups did not differ in clinical characteristics such as occurrence of rigidity, hypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions. The epsilon4++ allele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of onset. Patients with two epsilon4 alleles had earlier age at onset of dementia than those with no epsilon4 allele (63 +/- 9 versus 68 +/- 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 alleles had lowest scores on memory tests and differed significantly from those with one or zero epsilon4 allele in the delayed list learning (p<0.05) and from those with zero epsilon4 allele in the immediate and delayed story recall. In contrast, verbal functions were better preserved in two epsilon4 patients than in those with other ApoE genotypes. This study failed to confirm the earlier reports of severe aphasia, agnosia, and apraxia in familial AD patients, but the clinical phenotype was similar irrespective to the familial aggregation. However, AD patients with two epsilon4 alleles are characterized by more severe memory loss and earlier age of onset than those without the epsilon4 allele.

Age of Onset↗