Original Article
A Population-Based Study of Dementia in 85-Year-Olds
N Engl J Med 1993; 328:153-158January 21, 1993
- 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.
Media in This Article
Table 1
Procedures in the Diagnosis of Dementia.Table 2
Prevalence of Dementia in Relation to Sex and Severity.Article Activity
- Article
Dementia has become a major health problem because of the worldwide increase in elderly populations, especially those 80 years of age or older1. From the results of 47 studies, the prevalence of moderate or severe dementia was estimated to be 10.5 percent among persons 80 to 84 years old and 20.8 percent among those 85 to 89 years old2. Few people were studied in these age groups, which makes the available prevalence figures uncertain2.
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 studies1,4,5. 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 population1,6.
The present study was conducted as part of the longitudinal gerontologic and geriatric population studies in Gothenburg, Sweden7-9. 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 elsewhere7,8. 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 1Table 1
Procedures in the Diagnosis of Dementia.). 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.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 2Table 2
Prevalence of Dementia in Relation to Sex and Severity.). 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.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 3Table 3
Proportion of Subjects with Various Causes of Dementia.). 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 4Table 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 5Table 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 6Table 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 countries1,2 and higher than reported from autopsy studies18-20 and dementia-evaluation units21,22. 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,18,23-25 and the exact relation between cerebrovascular disease and dementia is still not clear25,26. 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 studies27,28 were similar to those found in our study. The other two studies29,30 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 units1,20-22,28,29. 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 syndrome14,31-33. 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 changes31,33 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 stroke38,39 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 disease31-33,35,40.
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.
Appendix
Appendix
The Hachinski Ischemic Score. - References
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B. Karlsson, R. Sigström, M. Waern, S. Östling, D. Gustafson, I. Skoog. (2010) The prognosis and incidence of social phobia in an elderly population. A 5-year follow-up. Acta Psychiatrica Scandinavica 122:1, 4-10
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D.R. Gustafson, L. Melchior, E. Eriksson, V. Sundh, K. Blennow, I. Skoog. (2010) The ACE Insertion Deletion polymorphism relates to dementia by metabolic phenotype, APOEɛ4, and age of dementia onset. Neurobiology of Aging 31:6, 910-916
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Stefan Wiktorsson, Bo Runeson, Ingmar Skoog, Svante Östling, Margda Waern. (2010) Attempted Suicide in the Elderly: Characteristics of Suicide Attempters 70 Years and Older and a General Population Comparison Group. American Journal of Geriatric Psychiatry 18:1, 57-67
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Peter van Vliet, Roos C. van der Mast, Marianne van den Broek, Rudi G. J. Westendorp, Anton J.M. de Craen. (2009) Use of benzodiazepines, depressive symptoms and cognitive function in old age. International Journal of Geriatric Psychiatry 24:5, 500-508
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Simona Sacuiu, Deborah Gustafson, Boo Johansson, Valgeir Thorvaldsson, Stig Berg, Magnus Sjögren, Xinxin Guo, Svante Östling, Ingmar Skoog. (2009) The pattern of cognitive symptoms predicts time to dementia onset. Alzheimer's and Dementia 5:3, 199-206
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Björn Karlsson, Isak Fredén Klenfeldt, Robert Sigström, Margda Waern, Svante Östling, Deborah Gustafson, Ingmar Skoog. (2009) Prevalence of Social Phobia in Non-Demented Elderly From a Swedish Population Study. American Journal of Geriatric Psychiatry 17:2, 127-135
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Madeleine Zetterberg, Sara Landgren, Malin E. Andersson, Mona Seibt Palmér, Deborah R. Gustafson, Ingmar Skoog, Lennart Minthon, Dag S. Thelle, Anders Wallin, Nenad Bogdanovic, Niels Andreasen, Kaj Blennow, Henrik Zetterberg. (2008) Association of complement factor H Y402H gene polymorphism with Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147B:6, 720-726
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H. Luukinen, J. Jokelainen, K. Kervinen, Y. A. Kesäniemi, S. Winqvist, M. Hillbom. (2008) Risk of dementia associated with the ApoE ɛ4 allele and falls causing head injury without explicit traumatic brain injury. Acta Neurologica Scandinavica 118:3, 153-158
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P. R. Duberstein, S. P. Pálsson, M. Waern, I. Skoog. (2008) Personality and risk for depression in a birth cohort of 70-year-olds followed for 15 years. Psychological Medicine 38:05,
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B. E. Gay, K. I. Taylor, U. Hohl, M. Tolnay, H. B. Staehelin. (2008) The validity of clinical diagnoses of dementia in a group of consecutively autopsied memory clinic patients. The Journal of Nutrition Health and Aging 12:2, 132-137
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Pia Gudmundsson, Ingmar Skoog, Margda Waern, Kaj Blennow, Sigurdur Pálsson, Lars Rosengren, Deborah Gustafson. (2007) The Relationship Between Cerebrospinal Fluid Biomarkers and Depression in Elderly Women. American Journal of Geriatric Psychiatry 15:10, 832-838
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Camila Porto de Deco, Jarbas Francisco Fernandes do Santos, Vicente de Paula Prisco da Cunha, Leonardo Marchini. (2007) General health of elderly institutionalised and community-dwelling Brazilians. Gerodontology 24:3, 136-142
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