Does apolipoprotein E influence learning and memory in the nondemented oldest old?

The objective of this study was to analyze the relationship of the apolipoprotein E (apoE) epsilon4 and epsilon2 alleles to learning and memory performances in the nondemented oldest old. Forty-six nondemented persons aged 85 years or over from a randomly selected group of 128 subjects in Vantaa, Finland, were studied. ApoE genotyping was performed using the minisequencing technique. A structured clinical examination and interview were carried out. The test variables studied were learning and memory scores (from the Fuld Object-Memory Evaluation), verbal fluency, and conceptualization (the Similarities subtest of the WAIS-R). We compared apoE-epsilon4 carriers to noncarriers and apoE-epsilon2 carriers to noncarriers. No statistically significant differences were found in any of the test variables. The results failed to confirm the hypotheses that poor cognitive performance is associated with the apoE-epsilon4 allele and good performance with the apoE-epsilon2 allele in the oldest old. This suggests that the apoE alleles do not have a detectable relationship to learning and memory in nondemented very elderly people.

Apolipoprotein E, cognitive function, and dementia in a general population aged 85 years and over.

We examined 510 subjects representing 83.2% of all citizens of a Finnish city aged 85 years or over. Mini-Mental State Examination (MMSE) scores, diagnosis of dementia by DSM-III-R criteria, and Apo-E genotype were determined. The prevalence of dementia was 38.6%. The odds ratio (OR) of the Apo-E epsilon4 carriers (with the reference population of people with the genotype epsilon3/epsilon3) for dementia was 2.36 (95% CI 1.58 - 3.53). There was a significant sex difference: The OR in women was 3.23 (95% CI 2.02 - 5.17) whereas among men it was insignificant. The mean MMSE score (+/- SD) among the Apo-E epsilon4 carriers (15.0 +/- 10.0) and noncarriers (18.7 8.6) (p < .001) differed among the whole population, but not within the demented or nondemented subjects analyzed separately. This study does not support the hypothesis that the Apo-E epsilon4 allele impairs cognitive functions of nondemented elderly, at least in those surviving to very old age.

APOE epsilon4 does not predict mortality, cognitive decline, or dementia in the oldest old.

OBJECTIVE: To examine the effect of the epsilon 4 allele on cognitive decline in the oldest old. METHODS: We studied all 601 citizens of the city of Vantaa age 85 years and older in 1991. A total of 553 subjects (92%) took part in the study, which used the Mini-Mental State Examination (MMSE) and assessment of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, third ed., revised (DSM-III-R) criteria. The survivors were re-examined 3 years later. APOE genotype was determined in 510 subjects, representing 83.2% of the original population. RESULTS: Approximately one-half of the subjects (n = 250) died before the follow-up, and 253 subjects (97.3% of the survivors) were re-examined. The occurrence of the APOE epsilon 4 allele did not have any significant effect on survival. Of the 187 previously nondemented subjects, 58 (31%) had developed dementia. The OR for the epsilon 4 carriers to develop dementia was not significant: OR = 1.78; 95% CI = 0.88 to 3.60. In individuals with a follow-up MMSE score (n = 222), the mean decline in the score was 3.1 points. APOE epsilon 4 carrier status did not have a significant effect on the mean MMSE change except in the previously demented subjects, among whom the drop was larger in the APOE epsilon 4 carriers. CONCLUSIONS: The lack of association between APOE epsilon 4 carrier status and mortality, or development of dementia, or cognitive decline in these very elderly people, whether analyzed in the whole population or among the nondemented subjects only, suggests that the APOE epsilon 4 effect in younger subjects is age-dependent, and that it is no longer present in very old age.

Apolipoprotein E phenotypes, dementia and mortality in a prospective population sample.

OBJECTIVE: To study the relationships between apoE phenotypes, dementia, and mortality. SETTING: A population-based study in Helsinki, Finland (the Helsinki Ageing Study). DESIGN: A prospective birth cohort study with 5-year follow-up. PARTICIPANTS: A total of 550 subjects of three birth cohorts of 75 (n = 182), 80 (n = 185), and 85 (n = 183) years of age. MEASUREMENTS: ApoE phenotype was determined from baseline blood samples. The cognitive function of the subjects was tested at baseline and at a 5-year follow-up using the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Diagnosis and type of dementia were determined by a neurologist. The cohorts were followed for 5 years, and causes of death were determined. Cox proportional hazards model was used for survival analyses. Analyses were performed comparing the apoE e4 allele and others. RESULTS: At baseline, the apoE e4 allele was found in 148 of 550 subjects (27%), in 24% of nondemented persons, in 51% of patients with probable or uncertain Alzheimer's disease (AD), and in 34% patients with vascular dementia. The CDR score was worse among subjects with an e4 allele compared with others at baseline (P < .001) and after a 5-year follow-up (P = .007). The crude mortality rates of subjects with and without an e4 allele were 48% (n = 71) and 37% (n = 148), respectively. After controlling for age and gender, the hazard ratio of an e4 allele was 1.61 (95% CI, 1.21-2.14) for all-cause mortality, deaths caused by dementia 2.20 (95% CI, 1.03-4.72), and presence of AD 3.24 (95% CI, 1.67-6.25). CONCLUSIONS: In a population aged 75 to 85 years, the presence of an apoE e4 allele is associated with impaired cognitive function, clinical dementia, AD, and excess 5-year mortality resulting from dementia and all causes.

Functional assessment scales in detecting dementia.

AIM: to evaluate the use of different functional scales in detecting dementia in a population study. METHODS: the study is part of the Helsinki Ageing Study. A random sample of 795 subjects aged 75 (n = 274), 80 (n = 266) and 85 years (n = 255) was taken. The prevalences of dementia (DSM-III-R criteria) in these age groups were 4.6, 13.1 and 26.7% respectively. The functional scale scores were known for 71% of the non-demented and 66% of the demented subjects. A structured questionnaire completed by a close informant included four functional scales: the index of activities of daily living (ADL), the modified Blessed dementia scale (DS), the instrumental activities of daily living scale (IADL) and the Functional Assessment Questionnaire (FAQ). RESULTS: all the functional scales discriminated demented from non-demented subjects. Based on receiver operating characteristics analysis, the area under the curve (95% confidence interval) was 0.90 (0.80-0.94) for the ADL, 0.94 (0.87-0.97) for the DS, 0.95 (0.90-0.98) for the IADL and 0.96 (0.92-0.98) for the FAQ. The effects of age, sex and education in detecting dementia were minor or non-existent in the ADL, DS and FAQ scales, but age had an effect on the performance of the IADL scale. All the scales detected even mild dementia adequately. CONCLUSIONS: functional scales can be used in detecting dementia when functional assessment is already used for other purposes, such as among elderly primary care patients.

One-year risk of institutionalization in demented outpatients with caretaking relatives.

In order to determine the factors associated with good and poor 1-year prognosis of demented patients, the caretakers of 100 home-based patients attending a specialist memory clinic were interviewed. After the follow-up, 71% continued to live at home. Mild dementia, independence in activities of daily living, fair independence in functions of instrumental activities of daily living, and lack of depression were clear signs for a good prognosis. Some patients with severe dementia and poor functional capacity continued to live at home. Continuing home care was also more likely if memory impairment, as opposed to functional problems, was expressed as the main concern. The proportion of caretakers mentioning memory decline as the main problem decreased during 1 year from 38% to 9% and the proportion mentioning functional problems increased from 48% to 64% among those continuing in home care. Memory disturbances are the first to appear and cause problems, but only functional decline threatens living at home.

Major depression in the elderly: a population study in Helsinki.

The aim of the study was to estimate the prevalence of major depression and to evaluate associated features in random age cohorts of 75, 80, and 85 years (N = 651). A clinical examination was made by experienced health center physicians, and major depression was diagnosed according to DSM-III criteria. The prevalence increased with age and was 1% to 4% in the age groups of 75 and 80 years, but 13% at the age of 85 years. No sex difference was found. The frequency of major depression was fourfold among institutionalized patients (16%) as compared to those living at home (4%). Major depression was strongly associated with objective health, intellectual functioning, and functional capacity. Depression was most common in subjects suffering from poor vision, urinary incontinence, or Parkinson's disease (odd ratios 4.2 to 4.9). Depression was also correlated with musculoskeletal disorders, coronary heart disease, and cerebrovascular diseases (odd ratios 2.5 to 3.4). The survey suggests that major depression is quite rare in healthy elderly people but common in disabled institutionalized patients.

Usefulness of the Clinical Dementia Rating scale in screening for dementia.

The Clinical Dementia Rating (CDR) scale is a qualitative staging instrument that has traditionally been used for assessing the severity of dementia. We used it for screening dementia in a population study of 75-, 80-, and 85-year-old people. The modified CDR scale was easy to establish and it proved to be useful in screening dementia. A more thorough examination is needed in the second phase to identify the false positives. The sensitivity of the CDR scale was 95% and the specificity 94%.

Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data.

We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health-related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases.

Staging the severity of dementia: comparison of clinical (CDR, DSM-III-R), functional (ADL, IADL) and cognitive (MMSE) scales.

The Helsinki Aging Study is based on a random sample of 795 subjects aged 75 years (N = 274), 80 years (N = 266) and 85 years (N = 255). Ninety-three demented patients were found. All were assessed for severity of dementia by Clinical Dementia Rating (CDR) scale by a general practitioner and according to the DSM-III-R criteria by a neurologist. The Mini-Mental State Examination (MMSE) was carried out by a community nurse and the Index of ADL and the IADL-scale by a close informant. The correlation of the severity of dementia between the DSM-III-R criteria and the CDR scale was moderate. The overall agreement was 64.5% and the Kappa index 0.56. The CDR scale tended to put patients in milder categories than the DSM-III-R criteria. The correlation between the clinical scales and categorized MMSE was moderate to fair. The overall agreement between MMSE and DSM-III-R criteria was 64% (Kappa 0.44) and between MMSE and CDR scale 55% (Kappa 0.33%). The dispersion of the functional scales (ADL, IADL) was much greater indicating that there were also other factors influencing the functional capacity than the degree of dementia. Different methods in staging dementia give different results thus influencing for instance the results of epidemiological studies. Functional scales are needed in clinical practice in addition to the assessment of the severity of dementia. The CDR scale is useful in assessing the need for support services.

Prevalence of dementia in the city of Helsinki.

The Helsinki Aging Study is based on a random sample of 795 subjects aged 75-years (N = 274), 80-years (N = 266) and 85-years (N = 255). A clinical examination including Clinical Dementia Rating (CDR)-scale was carried out in 82% of the cases. 93 demented subjects were found, 17 of whom had mild dementia. The prevalence of moderate and severe dementia was 2.9%, 10.3% and 23.3% in the age groups of 75-year-olds, 80-year-olds and 85-year-olds, respectively. If we take into account also the mild cases, we get the prevalence of dementia 4.6%, 13.1% and 26.7% in the above mentioned age groups, respectively. The proportion of mild dementias was lower than expected, which probably reflects both the difficulties to recognize mild dementia in an elderly population and the relatively small compensatory capacity of elderly people.

A programme for assigning target values for external quality assessment schemes in countries with no authorized reference laboratories. Annex. Experiences with deviating results on Ektachem 700 XR.

The use of consensus values in external quality assessment schemes (EQAS) involves several problems and should preferably be replaced with target values obtained by methods of high metrological level. However, such values are difficult to obtain. In the present study we transferred values from the NIST (former NBS) certified reference serum SRM 909 to lyophilized and frozen test sera for various inorganic components using flame absorption or flame emission spectrometry. Enzyme values were assigned by laboratories of members of the former Scandinavian Enzyme Committee. The assignment was based on 2-4 determinations each day through 3 days of experiment. A total of 10 laboratories participated in the work. The results were utilized in a Danish EQAS. One practical concern is the fairly long time (9 months) which was needed for production, collection and compiling all data. To get an impression of how much dry chemistry analysers, e.g, could influence consensus values a Kodak Ektachem 700 XR was studied using lyophilized and frozen sera. The results are reported in the annex. On NIST SRM 909 the values found for sodium(I) were 6% too high even though the findings on frozen human sera were accurate. For aspartate aminotransferase a result three times the target values was found on a human lyophilized serum, while the values on the frozen sera only were slightly too high.

The demented elderly in the city of Helsinki: functional capacity and placement.

OBJECTIVE: To study prevalence, functional capacity, and placement of demented patients in a randomly selected population. DESIGN: Survey. SETTING: Random sample from population registry of the City of Helsinki. PARTICIPANTS: Nine hundred subjects aged 75 years, 80 years and 85-years, 300 in each group. MEASUREMENTS: For each participant, we completed a questionnaire for the subject and an informant and a functional-capacity scale and Mini-Mental Status Examination by a community nurse, including the Clinical Dementia Rating (CDR) scale. Subjects with CDR of 0.5 or greater were examined by a neurologist who diagnosed the presence or absence of dementia according to DSM-III-R. RESULTS: Ninety-three subjects of the 656 whose CDR was known were found to have dementia. Three-quarters of them lived in institutions, and they comprised 33%, 60%, and 68% of all institutionalized patients in the above-mentioned age groups, respectively. Community residents suffering from dementia often lived with a caring relative and needed many services. A considerable part of the need was not met. CONCLUSIONS: In the older age groups, the need for institutional placement due to dementia is great. According to our study, it seems unlikely that these patients could be cared for in any other way, at least not on a large scale. The need for services for home-dwelling patients is also great, and the relatives carry a heavy load in taking care of demented patients.

Correction for age, education and other demographic variables in the use of the Mini Mental State Examination in Finland.

The population-based Helsinki Aging Study was comprised of three age groups: 75-, 80- and 85-year-olds. A random sample of 511 subjects completed the Mini Mental State Examination (MMSE) and were assessed on the Clinical Dementia Rating-scale (CDR). According to the CDR results 446 subjects were screened as non-demented. Of these subjects 30% scored below or at 24 MMSE points. Age, education and social group had a significant effect on the MMSE scores, even after excluding the demented cases. Together they explained 10% of the total variance within the MMSE. Social group correlated with education. The MMSE scores were corrected according to age and education. Adjustment of the originally used cutpoint of 24 resulted in cutpoints of 25 and 26 among the 75-year-olds, in the low and high education groups respectively; 23 and 26 in the 80-year-olds; 22 and 23 in the 85-year-olds.