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Volume 328:153-158 January 21, 1993 Number 3 Next

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ABSTRACT

Background The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden.

Methods The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history.

Results The prevalence of dementia was 29.8 percent (147 subjects). The condition was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. There were no significant sex-related differences in prevalence or severity. Of the subjects with dementia, 43.5 percent had Alzheimer's disease, 46.9 percent had vascular dementia (multi-infarct dementia in 34.6 percent, dementia related to cerebral hypoperfusion in 4.1 percent, and mixed dementia in 8.2 percent), and 9.5 percent had dementia due to other causes. The three-year mortality rate was 23.1 percent in the subjects without dementia, 42.2 percent in the patients with Alzheimer's disease, and 66.7 percent in the patients with vascular dementia. Infarcts detected by CT scanning were significantly more common in the subjects with dementia than in those without it (27.9 percent vs. 12.6 percent).

Conclusions Dementia was present in nearly a third of unselected 85-year-olds in Sweden. Almost half these subjects appeared to have vascular dementia, which may currently be more amenable to prevention or treatment than Alzheimer's disease.

Dementia is associated with more than 60 conditions, the two most common being Alzheimer's disease and vascular dementia³. For the etiologic diagnosis, a careful clinical evaluation is necessary, including a psychiatric and physical examination, an interview with a person close to the patient, computed tomography (CT) of the head, chest radiography, biochemical screening, and in selected cases, analysis of cerebrospinal fluid³. Such testing has not generally been possible in epidemiologic field studies^1,4,5. Therefore, current beliefs about the prevalence of different types of dementia are based on studies from dementia-evaluation units or findings at autopsy. Such studies, which generally report that 50 to 70 percent of the subjects with dementia have Alzheimer's disease, may not reflect the situation in the general population^1,6.

The present study was conducted as part of the longitudinal gerontologic and geriatric population studies in Gothenburg, Sweden^7,8,9. Its aim was to estimate the prevalence of dementia and its causes in a representative urban sample of 85-year-olds, some of whom had been followed for 15 years.

Methods

Subjects

All 85-year-old persons born between July 1, 1901, and June 30, 1902, and registered for census purposes in Gothenburg were invited to take part in a health survey. Informed consent was obtained from the subjects, their relatives, or both. The study was approved by the Ethics Committee for Medical Research at the University of Gothenburg. Both people living in the community and those in institutions were included. A systematic subsample of 826 subjects, comprising every second person from the census register, was selected for a psychiatric examination. The study was performed in three steps. First, a nurse visited the subject's home; then the subject was invited for an examination at the geriatric outpatient clinic of Vasa Hospital; and finally, the psychiatric examination was performed in the subject's home.

Forty-three subjects died before their examinations took place, leaving 783 subjects. Fourteen of these (1.8 percent) had moved or could not be traced, 229 (29.2 percent) declined all participation in the investigation, 17 (2.2 percent) took part only in the interview with the nurse, and 29 (3.7 percent) declined to be examined further after visiting the geriatric outpatient clinic. The 494 remaining subjects (63.1 percent), 143 men and 351 women, were finally examined by the psychiatrist. The nonparticipants (except for those who died before the examination) and the participants were compared with regard to sex, marital status, mortality rate over the next three years (to the age of 88), and status as psychiatric outpatients or inpatients in Gothenburg. No statistically significant differences were found with regard to these characteristics.

Psychiatric and Physical Examinations

The nurse's home visit and the examination at the geriatric outpatient clinic have been described in detail elsewhere^7,8. They included a physical examination by a geriatrician, a neuropsychological examination by a psychologist, laboratory tests including electrocardiography, chest radiography, and an extensive biochemical evaluation including a serum vitamin B₁₂ determination and thyroid-function tests.

All the psychiatric examinations were performed by one of the investigators in the subjects' homes or at institutions where the subjects were residents. The mean length of the examination was 83 minutes (range, 20 to 191). The examination was semistructured and included questions about background factors (i.e., history of stroke or transient ischemic attack, alcohol consumption, previous mental disorders, and current use of psychotropic drugs), ratings of psychiatric symptoms and signs with the Comprehensive Psychopathological Rating Scale,¹⁰ ratings of signs common in dementia (personality changes and motor symptoms), and tests of mental functioning (memory, comprehension of proverbs, language, apraxia, construction, finger agnosia, agraphia, alexia, acalculia, and right-left disorientation), including the Mini-Mental State Examination¹¹.

After the examination, the subject was asked to give the interviewer permission to interview another person close to the subject. In the case of subjects with dementia, a close informant was sought in other ways. Telephone interviews with informants were conducted by the same investigator for 451 subjects (91 percent). Forty subjects declined permission or did not have a close informant, and three potential informants declined to be interviewed. The mean length of the interview was 28 minutes (range, 9 to 65) for close informants of subjects without dementia, and 52 minutes (range, 15 to 95) for informants of subjects with dementia. The informant interview was semistructured and included questions about changes in the subject's behavior and intellectual function (i.e., changes in personality, memory, difficulties the subject had in finding his or her way in familiar surroundings, intellectual ability, language, psychiatric symptoms, activities of daily living, incontinence, and neurologic symptoms), background factors (i.e., history of stroke or transient ischemic attack, head trauma, infectious diseases, alcohol abuse, deficiency states, normal-pressure hydrocephalus, and brain tumors), and in subjects with dementia, questions about age at onset and course.

The mean interval between the examination at the outpatient clinic and the psychiatric examination was 2 weeks (range, 0 to 16); the mean interval between the psychiatric examination and the interview with a close informant was 5 months (range, 0 to 11).

All 147 subjects with dementia and a systematic subsample of 269 subjects without dementia were invited to undergo CT scanning of the head. One hundred four subjects with dementia and 135 subjects without dementia agreed. Within these two subgroups, there were no differences between the participants and the nonparticipants with regard to sex, marital status, mental disorders, institutionalization, three-year mortality, and cardiovascular disorders. All the CT scans were examined by two of the investigators. One hundred thirty-three scans were performed with a Philips Tomoscan 310 and 106 with a General Electric 8800 scanner.

The first 165 study participants were invited to undergo lumbar puncture. Sixty-nine subjects (31 with dementia and 38 without) accepted. The medical records for the subjects with dementia from psychiatric and geriatric institutions and outpatient departments in Gothenburg were also examined.

Diagnostic Procedures

The diagnosis of dementia was made on the basis of the psychiatric examination and the interview with the close informant, with each considered separately, and the criteria in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) (DSM-III-R)¹² were used. Each symptom had to have attained a level at which it caused the subject substantial difficulty in social functioning. A final diagnosis was made on the basis of the combined information with the use of four diagnostic steps (Table 1). The final diagnosis and its rating of severity were established according to the DSM-III-R¹². The duration of dementia had to be at least six months.

View this table: [in this window] [in a new window]   Table 1. Procedures in the Diagnosis of Dementia.

 
Subjects with dementia were classified into subgroups according to the cause of the dementia: Alzheimer's disease, defined according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association¹³; vascular dementia (multi-infarct dementia, probable vascular dementia or mixed dementia, and hypoperfusion dementia), defined according to the criteria proposed by Erkinjuntti et al.¹⁴; and other causes, defined according to the same criteria¹⁴. Within the category of vascular dementia, multi-infarct dementia was diagnosed when either or both of the following were present: one or more infarcts detected by CT scanning and a temporal connection (within one year) between the first symptoms of dementia and a history of acute focal neurologic symptoms and signs (restricted to definite symptoms or signs, such as acute hemiparesis or acute motor aphasia). Probable vascular dementia or mixed dementia was diagnosed when there was a history of acute focal neurologic symptoms and signs without a clear temporal connection with the evolution of dementia (over a period of more than one year). Hypoperfusion dementia was diagnosed when there was a temporal connection between the onset of dementia and a history of severe systemic hypotension. Other causes were diagnosed when the dementia evolved in temporal association with a neurologic, mental, or systemic disorder of sufficient severity to produce dementia. All the criteria were closely related to those in the DSM-III-R¹².

The Hachinski ischemic score,¹⁵ an often-used checklist of clinical features known to be common in multi-infarct dementia (see the Appendix), was used, but only for comparison with other studies and not for the final etiologic diagnosis. Diseases that could contribute to dementia but were not considered the primary cause were recorded as proposed by Roth⁶. The etiologic diagnoses and the Hachinski ischemic scores were based on information gathered from all the examinations and from case records.

Interobserver reliability of assessment of symptoms and signs was found to be satisfactory by comparing simultaneous independent ratings by two of the investigators (Spearman rank-correlation coefficient,¹⁶ 0.76 to 1.00). Interobserver reliability was not studied with respect to the informant interview. Interobserver reliability was studied with regard to causes of dementia for all subjects with dementia by means of kappa statistics¹⁷. In the three main diagnostic categories, the observed agreement was 94.6 percent, with a kappa of 0.90 (P<0.001).

Statistical Analysis

Differences in proportions were tested for significance by Fisher's exact test¹⁶ with a two-tailed level of significance.

Results

Prevalence of Dementia

The overall prevalence of dementia was 29.8 percent (Table 2). Among all the subjects, dementia was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. The results were similar for men and women.

View this table: [in this window] [in a new window]   Table 2. Prevalence of Dementia in Relation to Sex and Severity.

 
Causes of Dementia

Among all the subjects with dementia, 46.9 percent had vascular dementia, 43.5 percent had Alzheimer's disease, and 9.5 percent had dementia due to other causes (Table 3). The prevalence of Alzheimer's disease was roughly the same among men and women; vascular dementia was more common among women, although this difference was not significant (P = 0.061); and dementia due to other causes was more common among men (P = 0.002). The severity of dementia according to cause is shown in Table 4.

View this table: [in this window] [in a new window]   Table 3. Proportion of Subjects with Various Causes of Dementia.

 

View this table: [in this window] [in a new window]   Table 4. Severity of Dementia in Relation to Cause.

 
The rate of institutionalization was 1.7 percent for the subjects without dementia, 37.5 percent for those with Alzheimer's disease, 62.3 percent for those with vascular dementia, and 28.6 percent for those with other causes of dementia (P<0.001 for the comparison with subjects without dementia, and P = 0.005 for the comparison of Alzheimer's disease with vascular dementia).

Other concomitant disorders that can cause dementia but were not considered to be its main cause included vitamin B₁₂ deficiency (in nine subjects), alcohol abuse (in eight), temporal arteritis (in eight), severe cardiovascular disease (in three), depression (in three), chronic schizophrenia (in two), hypothyroidism (in two), and the following in one subject each: normal-pressure hydrocephalus, syphilis, infectious disease, multiple diseases, hyperthyroidism, hypercalcemia, borrelia infection, and epilepsy.

CT scanning in the subjects with dementia showed postoperative subdural hematoma in one subject and indicated normal-pressure hydrocephalus in four, among whom the diagnosis was confirmed in one. The relation between infarcts detected by CT scanning and dementia is shown in Table 5.

View this table: [in this window] [in a new window]   Table 5. Cerebral Infarcts Detected by CT Scanning in 85-Year-Old Persons.

 
Cerebrospinal fluid was analyzed in 31 subjects with dementia; none of these analyses revealed pathological changes indicating a secondary cause of dementia.

The mean (±SD) age at the onset of Alzheimer's disease was higher among those with mild dementia (82.3 ±2.7 years) than among those with moderate dementia (79.5 ±4.5 years, P = 0.019), and higher among those with moderate dementia than among those with severe dementia (75.5 ±7.4 years, P = 0.047). There were no significant differences in the subjects' mean ages at the onset of vascular dementia, according to the severity of dementia.

The three-year mortality was 23.1 percent for subjects without dementia, as compared with 42.2 percent for those with Alzheimer's disease (P = 0.003), 66.7 percent for those with vascular dementia (P<0.001), and 57.1 percent for those with dementia from other causes (P = 0.008). The three-year mortality differed significantly between subjects with Alzheimer's disease and those with vascular dementia (P = 0.005).

The results of analyses using alternative definitions of vascular dementia or different samples of subjects are given in Table 6.

View this table: [in this window] [in a new window]   Table 6. Proportion of Subjects with Vascular Dementia among All Subjects with Dementia, When Different Definitions or Samples are Used.

 
Discussion

The prevalence of vascular dementia in this study (46.9 percent if subjects with mixed dementia are included) was higher than in most population studies from Western countries^1,2 and higher than reported from autopsy studies^18,19,20 and dementia-evaluation units^21,22. A problem encountered in comparing different types of studies is the selection bias in studies from evaluation units and in autopsy materials, and the diagnostic uncertainty inherent in epidemiologic studies¹. However, in hospital-based studies using the same criteria and the same extensive clinical evaluation that we used, the clinical diagnosis of Alzheimer's disease was confirmed at autopsy in 80 to 90 percent of subjects,^1,3,20 and that of multi-infarct dementia in 80 percent¹⁴. It must be emphasized, however, that the accuracy of the diagnoses has not been studied in population samples. Unfortunately, there are currently no definite antemortem markers for Alzheimer's disease and vascular dementia, and the clinical and pathological diagnoses are controversial. The pathological findings show an overlap with the characteristics of normal aging,^18,23,24,25 and the exact relation between cerebrovascular disease and dementia is still not clear^25,26. The validity of the etiologic diagnosis in the present study may, however, be supported by the finding that the age at the onset of disease differed significantly among subjects with Alzheimer's disease with differing severities of dementia, but not among subjects with vascular dementia, and by the fact that mortality among subjects with vascular dementia was higher¹.

Four recent epidemiologic studies used detailed clinical diagnostic procedures, including CT scanning in some cases, to assess subjects identified in population surveys as having dementia. The relative proportions of vascular dementia and Alzheimer's disease in two of these studies^27,28 were similar to those found in our study. The other two studies^29,30 found a very low prevalence of vascular dementia, but subjects living in institutions were excluded, and many subjects died between screening and examination. If we had studied only noninstitutionalized subjects and excluded those who died within 16 months (the interval between screening and examination in the study of Evans et al.³⁰), the proportion of subjects with Alzheimer's disease would have been 61 percent, and that of subjects with vascular dementia, 25 percent. Furthermore, other studies have included subjects in all age groups, and most have been under the age of 80⁶.

The use of different criteria may also contribute to differences in prevalence figures. The Hachinski ischemic score¹⁵ has been used extensively in both epidemiologic studies and evaluation units^{1,20,21,22,28,29}. If we had used this approach, 60 percent of the dementias would have been classified as vascular or mixed.

A further reason for the high proportion of vascular dementia may be the extensive examinations and collection of information. This might also lead to lower proportions of Alzheimer's disease -- today largely a diagnosis of exclusion¹³. The incidence of Alzheimer's disease may be underestimated in patients in whom both Alzheimer's encephalopathy and vascular dementia contribute to dementia³¹. In this study, cases of mixed dementia were included among the vascular dementias to point to a group in which vascular factors probably contribute to the dementia syndrome^14,31,32,33. Indeed, if the Hachinski scoring¹⁵ had been applied, all the subjects with mixed dementia would have been classified as having multi-infarct dementia.

Vascular dementia may also have been underestimated, however. First, the symptoms used as the criteria for vascular dementia were limited to definite focal symptoms and signs. Second, small infarctions are often invisible on CT scans,²¹ and cerebral areas may be damaged and nonfunctional even though the CT scan remains normal³⁴. Third, many infarcts are clinically silent³⁵. Furthermore, 30 percent of the subjects with dementia did not have a CT scan. Finally, in making the diagnosis of vascular dementia, we did not use as criteria other vascular factors that might cause dementia or contribute to it -- such as white-matter changes^31,33 and severe cardiovascular diseases.

Clinical studies of vascular dementia report infarcts detected by CT scanning in 20 to 80 percent of cases,^36,37 but the presence of infarcts on CT scanning or a history of stroke does not necessarily mean that these factors caused the dementia. The finding that infarcts on CT were significantly more common in the subjects with dementia than in those without lends support to the use of this information in diagnosis. However, there was a wide overlap between the groups.

The general opinion that Alzheimer's disease is more common in women, and vascular dementia in men,^1,2 was not confirmed in our study. The low prevalence of dementias with other causes is in accord with results from other population studies. Concomitant diseases are a diagnostic problem in dementia of old age³. In cases with abnormal findings -- i.e., hypothyroidism, vitamin B₁₂ deficiency, or depression -- the mode of onset, clinical course, and response to treatment determine whether the findings should be regarded as a cause of dementia or as merely coincidental.

Most cases of dementia occur after the age of 80. To our knowledge, this is the most comprehensive study of the prevalence of dementia in a population of this age. The prevalence of vascular dementia was higher than has been generally reported in European and North American studies, even though mortality rates from stroke in Sweden are among the lowest in the world³⁸. Mortality from stroke^38,39 and the incidence of stroke³⁹ have declined in most Western countries during recent years. Increased survival among victims of stroke³⁹ may, however, lead to increasing rates of vascular dementia.

The emergence of evidence that vascular dementia may be more common than previously supposed³¹ may have important implications, because the possibilities of preventing or postponing atheromatosis and embolization through dietary changes, withdrawal from smoking, aspirin treatment, treatment of hypertension, and treatment of atrial fibrillation suggest that vascular dementia may at present be more amenable to prevention and treatment than Alzheimer's disease^{31,32,33,35,40}.

View this table: [in this window] [in a new window]   The Hachinski Ischemic Score.

 
Supported by grants from the Swedish Medical Research Council (90-27X-09131-01A), the Delegation for Social Research within the Ministry of Health and Social Affairs, the Goteborg Medical Services and Social Services Administrations, the Bank of Sweden Tercentenary Foundation, the Stiftelsen Soderstrom-Konigska sjukhemmet, Konung Gustaf V:s och Drottning Victorias Stiftelse, Stiftelsen for Gamla Tjanarinnor, Handlanden Hjalmar Svenssons Forskningsfond, the Swedish Society of Medicine, Stiftelsen Prof Gadelius Minnesfond, the Goteborg Medical Society, and Alzheimerfonden.

We are indebted to Ms. Liselott Agren for technical assistance.

Source Information

From the Department of Psychiatry, Sahlgrenska Hospital (I.S., L.N.), and the Department of Radiology, Ostra sjukhuset (B.P., L.-A.A.), both in Gothenburg, Sweden; and the Section of Geriatric Medicine, Department of Medicine, University of Illinois, Chicago (A.S.).

Address reprint requests to Dr. Skoog at the Department of Psychiatry, Sahlgrenska Hospital, S-413 45 Gothenburg, Sweden.

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Appendix

Abstract Letters Letters Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Related Letters:

Plasma Endothelin and the Hepatorenal Syndrome
Agarwal R., Nurnberger W., Moore K.
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N Engl J Med 1993; 329:63, Jul 1, 1993. Correspondence

A Population-Based Study of Dementia in 85-Year-Olds
Roman G. C., Goldstein M., Monfort J.-C., Skoog I., Nilsson L., Svanborg A.
Extract | Full Text  
N Engl J Med 1993; 329:63-64, Jul 1, 1993. Correspondence

Sex and Swedish 85-Year-Olds
Skoog I.
Extract | Full Text  
N Engl J Med 1996; 334:1140-1141, Apr 25, 1996. Correspondence

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