Kati Juva

Apolipoprotein E Phenotypes, Dementia and Mortality in a Prospective Population Sample

OBJECTIVE: To study the relationships between apoE phenotypes, dementia, and mortality.

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.

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 Parkinsons 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.

Atrial Fibrillation, Stroke, and Cognition A Longitudinal Population-Based Study of People Aged 85 and Older

Background and Purpose— The aim of this study was to investigate the association between atrial fibrillation (AF), stroke, dementia, and their correlation with brain pathology in subjects aged 85 years or older. Methods— This is a prospective 9-year follow-up population based study in Vantaa, a town in Southern Finland; 553 subjects (92% of the total population) aged 85 years or older were clinically examined by a neurologist. The presence of AF was collected from the medical records or examined by ECG or ambulatory ECG. Neuropathological examination was conducted in more than half of the clinically examined subjects. Results— AF was significantly associated with stroke at baseline; 32% of patients with AF had clinical evidence of stroke compared with 16.7% of those without such evidence (P<0.001). Dementia at baseline was significantly associated with age, clinical stroke, and the presence of apolipoprotein E ϵ4 allele, but not with sex, education, or vascular risk factors. Multiple regression analysis including neuropathological results showed that dementia was significantly associated with education (OR, 0.89; 95% CI, 0.80 to 0.98; P=0.019), the β-amyloid load in the brain (OR, 1.26; 95% CI, 1.13 to 1.39; P<0.001) and with the vascular pathology (OR, 2.03; 95% CI, 1.14 to 3.62; P=0.016), but not with sex, age at death, apolipoprotein E ϵ4 allele, or vascular risk factors. Conclusions— AF is a significant and preventable risk factor for stroke but not for dementia in the very old. The etiology of dementia syndrome in the very old is multifactorial. Both Alzheimer disease pathology and vascular pathology, particularly multiple small infarcts, contribute to cognitive decline.

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.

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%.

Neuropathologic Findings of Dementia with Lewy Bodies (DLB) in a Population-based Vantaa 85+ Study

The consortium on dementia with Lewy bodies has established consensus guidelines for the neuropathologic diagnosis of dementia with Lewy bodies (DLB) including the likelihood that the neuropathologic findings associate with the clinical syndrome. Nevertheless, clinico-pathological correlations remain controversial. We applied the consensus guidelines for determining Lewy-related pathology (LRP) and evaluated the clinical presentation in the prospective, population-based Vantaa 85+ study consisting of individuals at least 85 years of age. LRP was seen in 36% of 304 subjects and categorized as follows: 3% brainstem-predominant, 14% limbic, 15% diffuse neocortical type (4% could not be categorized). The likelihood that the neuropathology predicts the DLB clinical syndrome was low in 6%, intermediate in 13%, and high in 13% of all 304 subjects. In the latter two groups, 77% were demented, 35% had at least one extrapyramidal symptom, and 15% had visual hallucinations. Surprisingly, DLB clinical features associated better with high neurofibrillary stage than with diffuse neocortical LRP. Moreover, the neurofibrillary stage, substantia nigra neuron loss, and grade of Lewy neurites in hippocampal CA2-3 region, each showed a significant association with the extent of LRP. In conclusion, the neuropathologic DLB in this very elderly population was common, but the clinical symptoms tended to associate better with severe neurofibrillary pathology than with extensive LRP.

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.

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.