Usefulness of repeated presentation of Mini-Mental State Examination as a diagnostic procedure--a population-based study.

MATERIAL AND METHODS: The 280 subjects who achieved 24 points or less in the Mini-Mental State Examination (MMSE) in the first survey of 1449 subjects were invited for a comprehensive diagnostic examination for dementia including medical history, thorough neurological and cardiovascular examinations and detailed neuropsychological evaluation, magnetic resonance imaging (MRI)-study, cerebrospinal fluid (CSF)-analysis, electrocardiogram (ECG), chest radiograph and blood tests after the first assessment. The MMSE was presented again. RESULTS: Out of 240 persons, 57 subjects were diagnosed as having dementia. When the cut-off point of 24 or less in the second MMSE was used, the sensitivity of the second MMSE was 82% and the specificity was 64%. The positive predictive value of the second MMSE was 42% and negative predictive value 92%. The non-demented subjects improved their MMSE score at the second examination. In contrast, the demented subjects maintained their low MMSE score at the second examination.

Midlife income, occupation, APOE status, and dementia: a population-based study.

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. 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, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.

Socioeconomic status and ischemic stroke: The FINMONICA Stroke Register.

BACKGROUND AND PURPOSE: It has been shown that low socioeconomic status is associated with death from stroke. More-detailed data have, however, remained scanty. The purpose of the present study was to examine the association of socioeconomic status with ischemic stroke. Besides mortality, we analyzed the incidence, case-fatality ratio, and prognosis of ischemic stroke events. METHODS: Our population-based study included 6903 first stroke events registered by the FINMONICA Stroke Register in 3 areas of Finland during 1983 to 1992. Indicators of socioeconomic status, such as taxable income and education, were obtained by record linkage of the stroke register data with files of Statistics Finland. RESULTS: Incidence, case-fatality ratio, and mortality rates for ischemic stroke were all inversely related to income. Furthermore, 28 days after the onset of symptoms, a greater proportion of patients with low income than of those with high income was still in institutionalized care and/or in need of help for their activities of daily living. Population-attributable risk of the incidence of first ischemic stroke due to low socioeconomic status was 36% for both sexes. For the death from first ischemic stroke, it was 56% for both sexes. CONCLUSIONS: Persons with low socioeconomic status have considerable excess rates of morbidity and mortality from ischemic stroke in Finland. A reduction in this excess could markedly decrease the burden of ischemic stroke to the society and thus constitute an important public health improvement.

Socioeconomic inequalities in the incidence, mortality and prognosis of subarachnoid hemorrhage: the FINMONICA Stroke Register.

Low socioeconomic status (SES) is associated with increased mortality from stroke, but usually no distinction is made between stroke subtypes. We analyzed the relationship of SES with mortality and morbidity of subarachnoid hemorrhage (SAH). In the FINMONICA Stroke Register, 956 consecutive SAH events were recorded during 1983-1992 in patients aged 25-74 years. We used taxable income stratified into three categories, low, middle, and high, as an indicator of SES. The age-standardized incidence of SAH among men and women aged 25-44 years was approximately three times higher in the low-income group than in the high-income group. In older individuals, differences between the income groups were less pronounced. Among survivors of the acute stage, a poorer prognosis was observed in patients with low income than in those with high income. In conclusion, there is a clear excess mortality and morbidity of SAH in young individuals with low income, particularly among men.

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.

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.

Socioeconomic differences in the incidence, mortality and prognosis of intracerebral hemorrhage in Finnish Adult Population. The FINMONICA Stroke Register.

We examined the association of socioeconomic status (SES) with the incidence, mortality and case fatality of intracerebral hemorrhage (ICH). During 1982-1992, 909 ICH events were registered among persons aged 25-74 years. Taxable income was used as an indicator of SES. It was stratified into three categories: low, middle and high. The age-standardized incidence and mortality of ICH were significantly higher in the low- than in the high-income group in both genders. Among men aged 25-59 years, the adjusted odds ratio (OR) of ICH death within 1 year after the onset of the event was twice as high in the low-income group as in the high-income group (OR = 2.12, 95% confidence interval 1.02-4.40). In conclusion, marked socioeconomic differences were found in the incidence and mortality of ICH, in particular among working aged men.

Trends in case-fatality of stroke in Finland during 1983 to 1992.

BACKGROUND AND PURPOSE: Stroke mortality has been declining in Finland during the past 20 years. It is not known, however, whether this favorable development is attributable to the decline in the incidence or case-fatality of stroke. For this reason we examined the trends in case-fatality of stroke, including trends by subtype of stroke. METHODS: The analyses were carried out using data of the community-based FINMONICA Stroke Register, which was operating in three geographic areas of Finland during 1983 to 1992. All stroke events (n = 11,171) in persons aged 35 to 74 years were included in this register. RESULTS: The 28-day case-fatality of stroke fell yearly by 3.6% (P = .01) in men and by 2.6% (P = .2) in women. At the end of the study period, the average 28-day case-fatality of all strokes was 20% in men and 21% in women. Considerable differences by subtype of stroke were observed. The 28-day case-fatalities at the end of the study period were in men-56% for subarachnoid hemorrhage, 42% for intracerebral hemorrhage, and 14% for cerebral infarction. In women, the corresponding figures were 49%, 49%, and 14%. The 28-day case-fatality of subarachnoid hemorrhage did not change during the study period, but for intracerebral hemorrhage, a significant decline was observed in men and there was a declining trend also in women. The 28-day case-fatality of cerebral infarction declined significantly in both genders. CONCLUSIONS: With the exception of subarachnoid hemorrhage, the 28-day case-fatality of stroke has fallen in Finland. It is likely that this fall has contributed to the decline in stroke mortality.

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).

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.

Psychometric discrimination of tetrahydroaminoacridine responders in Alzheimer patients.

Fourteen patients with probable Alzheimer's disease (AD) participated in an open tetrahydroaminoacridine (THA) treatment trial. Before initiation of THA treatment, a brief battery of neuropsychological tests was performed by an experienced neuropsychologist. The tests were repeated 120 min after a single dose of 50 mg THA had been administered perorally. Thereafter, the patients had a 4-week active treatment with THA 100 mg/day. After the treatment period, eight patients were defined as responders (increase of Mini-Mental State Examination score > or = 3) and six patients as nonresponders to the treatment. The responders showed significant improvement on Digit Span, Trail Making B, and on both Clock Setting and Clock Recognition tests after 50 mg of THA. The results suggest that in this subgroup of AD patients augmentation of the brain cholinergic systems mainly led to improvement of attentional and frontal-lobe rather than mnemonic functions.

Discrimination of Alzheimer patients responding to cholinesterase inhibitor therapy.

We have studied whether it is possible to discriminate responders to tacrine treatment from patients nonresponsive to tacrine in Alzheimer's disease. The results indicate that mildly demented patients will most likely gain a benefit of tacrine treatment. Neuropsychological tests on attention and working memory after a single dose of tacrine might be useful as well as a single dose pharmaco-EEG in discriminating responders to treatment.

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.

Discrimination of tetrahydroaminoacridine responders by a single dose pharmaco-EEG in patients with Alzheimer's disease.

We report the results of our study suggesting that a single dose pharmaco-EEG may predict treatment response to tetrahydroaminoacridine (THA) in Alzheimer's disease (AD). 14 AD patients and 7 age-matched neurologically healthy controls were selected for the study. AD patients had 7 weeks' THA treatment. 6 patients were regarded as responders and 8 patients as nonresponders, respectively. AD patients as well as controls had a baseline EEG recording and next day another recording 90 minutes after a peroral single dose of 50 mg THA. The relative change from the baseline in the alpha-theta ratio was the most sensitive discriminator of responders and nonresponders (P = 0.004, ANOVA).