Cause of Death in Alzheimer's Disease ALISTAIR BURNS, ROBIN JACOBY, PHILIP LUTHERT, RAYMOND LEVY
Introduction Alzheimer's disease (AD) is a progressive neurological disorder associated with an increased mortality rate [1, 2]. It affects about 6% of elderly people over the age of 65 and this prevalence rate trebles for those over 85 [3]. Although there has been progress in the last two decades in our understanding of the disorder, one aspect which has received remarkably little attention is the final cause of death [1]. The aim of the present study was to investigate the cause of death in AD as recorded on the death certificate and as found at post-mortem examination. Method All subjects were participants in a longitudinal study of patients satisfying the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA [4]) criteria for AD. These have been well validated neuropathologically [5, 6]. All were resident in the Camberwell Health Authority area (which comprises the South London boroughs of East Lambeth and South Southwark) and all had been seen at the only two psychiatric hospitals in the area as inpatients, day
patients, outpatients or on domiciliary consultations. The study consisted of annual assessments of cognitive function, mental state and computed tomography of the head. A request for autopsy was routinely made either before or at the time of death, and in all cases a copy of the death certificate was obtained. The present report is based on those who died during the first 3 years of the study. The primary cause of death was divided into 'nonspecific causes' (e.g. bronchopneumonia, respiratory failure, cardiorespiratory failure) or 'specific causes' (all other specified diseases such as myocardial infarction or pulmonary embolism). This classification was chosen to allow comparisons with previous studies [2, 7, 8]. It was also noted whether dementia was recorded on the certificate. In cases where autopsy was performed, the primary cause of death considered by the pathologist was noted. (Details of the neuropathological diagnoses will be reported elsewhere.)
Results One hundred and seventy-eight patients were recruited into the study. The mean age of the sample was 80.4 years (range 56-99 years), the mean age of onset was 75.2 years (range 50-95 years) and the mean duration of illness was 63 months (range 6-240 months). There were 140 Age and Ageing 1990:19:341 -344
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
Summary Bronchopneumonia was the commonest cause of death in 84 elderly patients suffering from Alzheimer's disease. The cause of death as stated on the death certificate agreed with the pathological diagnosis in 77% of cases. In 30%, no mention of the presence of a dementia syndrome was recorded on the death certificate. An increased willingness to record the presence of a dementia syndrome and a higher autopsy rate would increase the accuracy of death certification in Alzheimer's disease.
A. BURNS ET AL.
342
Table I. Cause of death in AD as recorded on death certificates (n = 84) Cause Primary: non-specific Bronchopneumonia Dementia Old age Total Primary: specific Cardiovascular disease Cerebrovascular disease Pulmonary embolus Septicaemia Renal failure Acute obstructive airways disease Total Secondary Senile dementia/dementia Alzheimer's disease 'Senile cardiovascular degeneration' None of the above Total
Number
%
57 1 1 59
tion of the presence of a dementia syndrome on the certificate despite very clear evidence in each case that the subject was demented. Seven patients had a contributory diagnosis of 'senile cardiovascular degeneration' (all were attributable to the same medical practitioner). Table II shows the pathological diagnoses in the 53 patients in whom autopsy was performed (12 from the Coroner's office). Bronchopneumonia was the commonest cause, followed by myocardial infarction (with or without cardiac arrhythmia). Dementia was considered the primary cause in one case in view of the absence of other significant disease. In 30 cases, the death certificate was signed before the autopsy was performed. In these cases, it was considered by the clinicians that the autopsy was purely for research purposes and there was no reason to doubt the cause of death. The pathologist's view agreed with the clinicians in 23 cases (77%). In the other seven, five had been considered due to non-specific causes by the clinicians but specific causes were found at autopsy—myocardial infarction (2 cases), pulmonary embolism, septicaemia and congestive cardiac failure. In two cases where the clinician had assigned stroke as the primary cause of death, the pathologists found bronchopneumonia and myocardial infarction to be the cause. In three cases, small extradural haematomata (considered to be clinically insignificant) were found. Four patients were found to have cancer—two with primary lung tumours (one diagnosed during life) and two with colonic
70
Table II. Cause of death in AD as determined at postmortem (n = 53)
13 2 4 4
Cause
1 1 25
30
37 15 7 25
44
84
100
18 8 30
Bronchopneumonia Myocardial infarction/cardiac arrhythmia Septicaemia Congestive cardiac failure Pulmonary embolism Renal failure Dementia Total
Number
O
o
34 6
64 11
4 3 4 1 1
8 5 8 2 2
53
100
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
women (79%) and 38 men (21 %) in the sample. During the first 3 years of follow-up, 84 had died (19 men and 65 women). Autopsies were carried out on 53 subjects (63%). The primary cause of death as reported on the death certificate is shown on Table I. Seventy per cent died of a non-specific cause, which included one patient to whom a primary diagnosis of dementia was assigned and another where 'old age' was put down as the main cause of death (the patient was aged 88 at the time of death). Subjects dying of non-specific causes were more likely to be in hospital than in their own or residential homes (*2 test 7.20, 2 df, p < 0.03). The majority dying of specific disorders did so from diseases affecting the cardiovascular system. Only two patients had cerebrovascular disease as the primary cause of death, reflecting the specific exclusion of vascular disease inherent in the N I N C D S / A D R D A criteria. Sixty-two per cent had either dementia/ senile dementia or AD as a contributory (secondary) cause of death; 30% had no men-
CAUSE OF DEATH IN ALZHEIMER'S DISEASE
tumours (both suspected during life, but neither confirmed).
Discussion
343
There were three main findings of this study. First, that agreement between the certified cause of death and that determined by autopsy was 77%. Second, that bronchopneumonia was the commonest mode of death, both as stated on the death certificate and proven at autopsy, in elderly AD patients. Third, that in one third of cases, no mention was made of the presence of a dementia syndrome on the death certificate. There is evidence that the clinically judged cause of death does not correspond to that found at autopsy. For example, Cameron and McGoogan [9] found that 42% of clinical diagnoses were not substantiated by autopsy. This was particularly true in cases of infection and cerebrovascular disease. Pulmonary embolism is underdiagnosed particularly often [10]. All four cases of pulmonary embolism in the current study were associated with sudden death, unexpected clinically, and all four were referred to the Coroner. The rate of agreement in this study between clinical and pathological diagnoses may be unrepresentatively high for three reasons. First, the scope for misdiagnosis was relatively small due to the homogeneity of the population and the fact that the majority died in hospital after a long illness. Second, the clinical diagnosis was not just the impression of Katzman [17] noted that, in the USA, AD the clinician (as has been used in other studies), rarely appeared on death certificates thus leadbut was the definitive diagnosis as recorded on ing to a gross underestimation of the prevalence the death certificate. It is possible that for some of the condition. As far as we are aware, ours is reason the diagnosis recorded on the certificate the first study to assess the proportion of cases was more accurate than that which would have in which dementia has been recorded on certifibeen given if the clinician had merely been cates. In only one case was 'dementia' consiasked his opinion as to the cause of death. dered to be the primary cause. As Katzman [17] Third, doubtful cases would have been referred has pointed out, a subject suffering from a to the Coroner biasing the sample to those cases primary lung neoplasm with a terminal bronwhere the diagnosis was fairly certain. The chopneumonia would have the former diagnostandard of accuracy of death certificates is low sis appearing first on the certificate but this is and recommendations have been suggested for not the case in dementia. Thirty per cent of improvements [11]. The autopsy examination cases in our sample had no mention of dementia is the ultimate validation of the clinical diagno- and the idiosyncratic (and probably unhelpful) sis [9] but in a small number of cases the cause of diagnosis of 'senile cardiovascular degeneradeath remains uncertain [12]. Autopsy rates are tion' did not convey sufficient information to declining with rates of only 20-30% common- allow the presence of dementia to be assumed.
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
place [12,13], and the success rate in the present study was due to a high level of contact with the relatives and the manner in which the request was made [14]. Kay [7] divided the cause of death in elderly psychiatric patients into specific (including cerebrovascular disease) and non-specific (bronchopneumonia) based on original work by Alstrom [15]. The justification for including bronchopneumonia as a non-specific cause was that the dementia led to a period of inanition resulting in a hypostatic pneumonia and death [7, 10]. Kay's study [7] was carried out to test the proposed distinction between functional and organic illness in the elderly. He showed that 90% of subjects with senile dementia died from non-specific causes, whereas functionally ill patients had similar proportions of specific and non-specific deaths compared with the general population. The proportion dying from bronchopneumonia in our study (70%) was very similar to that of Whitehead and Hunt [8] and Molsa et al. [2] who both found that 68% of patients succumbed to bronchopneumonia as the terminal event. Corsellis [16], in a neuropathological study, found that 20% of 101 cases of dementia died of bronchopneumonia. The reason for this lower proportion may be that his diagnoses were based on neuropathological examination and not death certification. Bronchopneumonia has also been found to be the commonest mode of death found in elderly medically ill geriatric patients [12].
344
A. BURNS ET AL.
In conclusion, over-reliance on the certified cause of death will lead to serious statistical inaccuracies. In particular, the prevalence of dementia in general and AD in particular will be significantly underestimated. Clinicians should be more aware of the importance of recording dementia on the death certificate and autopsies should be routinely sought in an attempt to improve the accuracy of death certification.
References 1. Christie A. Survival in dementia: a review. In: Arie T, ed. Recent advances in psychogeriatrics Edinburgh: Churchill Livingstone, 1985;33-44. 2. Molsa P, Marttila R, Rinne U. Survival and cause of death in Alzheimer's disease and multiinfarct dementia. Ada Neurol Scand 1986;74:103-7. 3. Bergmann K. Epidemiological aspects of dementia and considerations in planning services. Dan Med Bull 1985;32 (suppl. 1):84—91. 4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E. Clinical diagnosis of Alzheimer's disease. Neurology 1984;34:939-44. 5. Tierney M, Fisher R, Lewis A, et al. The NINCDS/ADRDA Workshop criteria for the clinical diagnosis of probable Alzheimer's disease. Neurology 1988;38:3 59-64. 6. Martin E, Wilson R, Penn R, Forkes J, Clasen R, Savoy S. Cortical biopsy results in Alzheimer's disease. Neurology 1987;37:1201-4.
Authors' address Section of Old Age Psychiatry, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF Received 17 January 1990
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
Acknowledgements We are grateful to Drs Janota and Honavar of the Neuropathology Department at the Institute of Psychiatry and the other pathologists involved in performing the autopsies. The current work was supported by a Medical Research Council project grant to R.L. and R.J. and in part through Medical Research Council funding of the Alzheimer's Disease Brain Bank.
7. Kay D. Outcome and cause of death in mental disorders of old age: a long-term follow-up of functional and organic psychoses. Ada Psychiatr Scand 1962;38:249-76. 8. Whitehead A, Hunt A. Elderly psychiatric patients: a 5-year prospective study. Psychol Med 1982;12:149-57. 9. Cameron H, McGoogan E. Necropsy: a yardstick for clinical diagnosis. Br Med J 1980;281:985-7. 10. Cameron H, McGoogan E. A prospective study of 1152 hospital autopsies: 2. Analysis of inaccuracies in clinical diagnosis and their significance. J' Pathol 1981; 133:285-300. 11. Medical aspects of death certification: a joint report of the Royal College of Physicians and the Royal College of Pathologists. J R Coll Phys (Lond) 1982;16:205-18. 12. Puxty J, Horan M, Fox R. Necropsies in the elderly. Lancet 1983;i:1262-4. 13. Birkett D. Differentiation between senile and arterosclerotic psychoses. Br J Psychiatry 1972;12O:321-5. 14. Burns A, Reith M, Jacoby R, Levy R. 'How to do it'—obtaining consent for autopsy in Alz1. heimer's disease. Int J Geriatr Psychiatr (in press). 15. Alstrom C. Mortality in mental hospitals with especial regard to tuberculosis. Ada Psychiatr Scand 1942;Suppl. 24. 16. Corsellis J. Mental illness in the aging brain. (Maudsley Monographs No. 9). Oxford: Oxford University Press, 1962. 17. Katzman R. The prevalence and malignancy of Alzheimer disease. Arch Neurol 1976;33:217-8.
Introduction Alzheimer's disease (AD) is a progressive neurological disorder associated with an increased mortality rate [1, 2]. It affects about 6% of elderly people over the age of 65 and this prevalence rate trebles for those over 85 [3]. Although there has been progress in the last two decades in our understanding of the disorder, one aspect which has received remarkably little attention is the final cause of death [1]. The aim of the present study was to investigate the cause of death in AD as recorded on the death certificate and as found at post-mortem examination. Method All subjects were participants in a longitudinal study of patients satisfying the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA [4]) criteria for AD. These have been well validated neuropathologically [5, 6]. All were resident in the Camberwell Health Authority area (which comprises the South London boroughs of East Lambeth and South Southwark) and all had been seen at the only two psychiatric hospitals in the area as inpatients, day
patients, outpatients or on domiciliary consultations. The study consisted of annual assessments of cognitive function, mental state and computed tomography of the head. A request for autopsy was routinely made either before or at the time of death, and in all cases a copy of the death certificate was obtained. The present report is based on those who died during the first 3 years of the study. The primary cause of death was divided into 'nonspecific causes' (e.g. bronchopneumonia, respiratory failure, cardiorespiratory failure) or 'specific causes' (all other specified diseases such as myocardial infarction or pulmonary embolism). This classification was chosen to allow comparisons with previous studies [2, 7, 8]. It was also noted whether dementia was recorded on the certificate. In cases where autopsy was performed, the primary cause of death considered by the pathologist was noted. (Details of the neuropathological diagnoses will be reported elsewhere.)
Results One hundred and seventy-eight patients were recruited into the study. The mean age of the sample was 80.4 years (range 56-99 years), the mean age of onset was 75.2 years (range 50-95 years) and the mean duration of illness was 63 months (range 6-240 months). There were 140 Age and Ageing 1990:19:341 -344
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
Summary Bronchopneumonia was the commonest cause of death in 84 elderly patients suffering from Alzheimer's disease. The cause of death as stated on the death certificate agreed with the pathological diagnosis in 77% of cases. In 30%, no mention of the presence of a dementia syndrome was recorded on the death certificate. An increased willingness to record the presence of a dementia syndrome and a higher autopsy rate would increase the accuracy of death certification in Alzheimer's disease.
A. BURNS ET AL.
342
Table I. Cause of death in AD as recorded on death certificates (n = 84) Cause Primary: non-specific Bronchopneumonia Dementia Old age Total Primary: specific Cardiovascular disease Cerebrovascular disease Pulmonary embolus Septicaemia Renal failure Acute obstructive airways disease Total Secondary Senile dementia/dementia Alzheimer's disease 'Senile cardiovascular degeneration' None of the above Total
Number
%
57 1 1 59
tion of the presence of a dementia syndrome on the certificate despite very clear evidence in each case that the subject was demented. Seven patients had a contributory diagnosis of 'senile cardiovascular degeneration' (all were attributable to the same medical practitioner). Table II shows the pathological diagnoses in the 53 patients in whom autopsy was performed (12 from the Coroner's office). Bronchopneumonia was the commonest cause, followed by myocardial infarction (with or without cardiac arrhythmia). Dementia was considered the primary cause in one case in view of the absence of other significant disease. In 30 cases, the death certificate was signed before the autopsy was performed. In these cases, it was considered by the clinicians that the autopsy was purely for research purposes and there was no reason to doubt the cause of death. The pathologist's view agreed with the clinicians in 23 cases (77%). In the other seven, five had been considered due to non-specific causes by the clinicians but specific causes were found at autopsy—myocardial infarction (2 cases), pulmonary embolism, septicaemia and congestive cardiac failure. In two cases where the clinician had assigned stroke as the primary cause of death, the pathologists found bronchopneumonia and myocardial infarction to be the cause. In three cases, small extradural haematomata (considered to be clinically insignificant) were found. Four patients were found to have cancer—two with primary lung tumours (one diagnosed during life) and two with colonic
70
Table II. Cause of death in AD as determined at postmortem (n = 53)
13 2 4 4
Cause
1 1 25
30
37 15 7 25
44
84
100
18 8 30
Bronchopneumonia Myocardial infarction/cardiac arrhythmia Septicaemia Congestive cardiac failure Pulmonary embolism Renal failure Dementia Total
Number
O
o
34 6
64 11
4 3 4 1 1
8 5 8 2 2
53
100
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
women (79%) and 38 men (21 %) in the sample. During the first 3 years of follow-up, 84 had died (19 men and 65 women). Autopsies were carried out on 53 subjects (63%). The primary cause of death as reported on the death certificate is shown on Table I. Seventy per cent died of a non-specific cause, which included one patient to whom a primary diagnosis of dementia was assigned and another where 'old age' was put down as the main cause of death (the patient was aged 88 at the time of death). Subjects dying of non-specific causes were more likely to be in hospital than in their own or residential homes (*2 test 7.20, 2 df, p < 0.03). The majority dying of specific disorders did so from diseases affecting the cardiovascular system. Only two patients had cerebrovascular disease as the primary cause of death, reflecting the specific exclusion of vascular disease inherent in the N I N C D S / A D R D A criteria. Sixty-two per cent had either dementia/ senile dementia or AD as a contributory (secondary) cause of death; 30% had no men-
CAUSE OF DEATH IN ALZHEIMER'S DISEASE
tumours (both suspected during life, but neither confirmed).
Discussion
343
There were three main findings of this study. First, that agreement between the certified cause of death and that determined by autopsy was 77%. Second, that bronchopneumonia was the commonest mode of death, both as stated on the death certificate and proven at autopsy, in elderly AD patients. Third, that in one third of cases, no mention was made of the presence of a dementia syndrome on the death certificate. There is evidence that the clinically judged cause of death does not correspond to that found at autopsy. For example, Cameron and McGoogan [9] found that 42% of clinical diagnoses were not substantiated by autopsy. This was particularly true in cases of infection and cerebrovascular disease. Pulmonary embolism is underdiagnosed particularly often [10]. All four cases of pulmonary embolism in the current study were associated with sudden death, unexpected clinically, and all four were referred to the Coroner. The rate of agreement in this study between clinical and pathological diagnoses may be unrepresentatively high for three reasons. First, the scope for misdiagnosis was relatively small due to the homogeneity of the population and the fact that the majority died in hospital after a long illness. Second, the clinical diagnosis was not just the impression of Katzman [17] noted that, in the USA, AD the clinician (as has been used in other studies), rarely appeared on death certificates thus leadbut was the definitive diagnosis as recorded on ing to a gross underestimation of the prevalence the death certificate. It is possible that for some of the condition. As far as we are aware, ours is reason the diagnosis recorded on the certificate the first study to assess the proportion of cases was more accurate than that which would have in which dementia has been recorded on certifibeen given if the clinician had merely been cates. In only one case was 'dementia' consiasked his opinion as to the cause of death. dered to be the primary cause. As Katzman [17] Third, doubtful cases would have been referred has pointed out, a subject suffering from a to the Coroner biasing the sample to those cases primary lung neoplasm with a terminal bronwhere the diagnosis was fairly certain. The chopneumonia would have the former diagnostandard of accuracy of death certificates is low sis appearing first on the certificate but this is and recommendations have been suggested for not the case in dementia. Thirty per cent of improvements [11]. The autopsy examination cases in our sample had no mention of dementia is the ultimate validation of the clinical diagno- and the idiosyncratic (and probably unhelpful) sis [9] but in a small number of cases the cause of diagnosis of 'senile cardiovascular degeneradeath remains uncertain [12]. Autopsy rates are tion' did not convey sufficient information to declining with rates of only 20-30% common- allow the presence of dementia to be assumed.
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
place [12,13], and the success rate in the present study was due to a high level of contact with the relatives and the manner in which the request was made [14]. Kay [7] divided the cause of death in elderly psychiatric patients into specific (including cerebrovascular disease) and non-specific (bronchopneumonia) based on original work by Alstrom [15]. The justification for including bronchopneumonia as a non-specific cause was that the dementia led to a period of inanition resulting in a hypostatic pneumonia and death [7, 10]. Kay's study [7] was carried out to test the proposed distinction between functional and organic illness in the elderly. He showed that 90% of subjects with senile dementia died from non-specific causes, whereas functionally ill patients had similar proportions of specific and non-specific deaths compared with the general population. The proportion dying from bronchopneumonia in our study (70%) was very similar to that of Whitehead and Hunt [8] and Molsa et al. [2] who both found that 68% of patients succumbed to bronchopneumonia as the terminal event. Corsellis [16], in a neuropathological study, found that 20% of 101 cases of dementia died of bronchopneumonia. The reason for this lower proportion may be that his diagnoses were based on neuropathological examination and not death certification. Bronchopneumonia has also been found to be the commonest mode of death found in elderly medically ill geriatric patients [12].
344
A. BURNS ET AL.
In conclusion, over-reliance on the certified cause of death will lead to serious statistical inaccuracies. In particular, the prevalence of dementia in general and AD in particular will be significantly underestimated. Clinicians should be more aware of the importance of recording dementia on the death certificate and autopsies should be routinely sought in an attempt to improve the accuracy of death certification.
References 1. Christie A. Survival in dementia: a review. In: Arie T, ed. Recent advances in psychogeriatrics Edinburgh: Churchill Livingstone, 1985;33-44. 2. Molsa P, Marttila R, Rinne U. Survival and cause of death in Alzheimer's disease and multiinfarct dementia. Ada Neurol Scand 1986;74:103-7. 3. Bergmann K. Epidemiological aspects of dementia and considerations in planning services. Dan Med Bull 1985;32 (suppl. 1):84—91. 4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E. Clinical diagnosis of Alzheimer's disease. Neurology 1984;34:939-44. 5. Tierney M, Fisher R, Lewis A, et al. The NINCDS/ADRDA Workshop criteria for the clinical diagnosis of probable Alzheimer's disease. Neurology 1988;38:3 59-64. 6. Martin E, Wilson R, Penn R, Forkes J, Clasen R, Savoy S. Cortical biopsy results in Alzheimer's disease. Neurology 1987;37:1201-4.
Authors' address Section of Old Age Psychiatry, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF Received 17 January 1990
Downloaded from http://ageing.oxfordjournals.org/ at City University, London on April 25, 2016
Acknowledgements We are grateful to Drs Janota and Honavar of the Neuropathology Department at the Institute of Psychiatry and the other pathologists involved in performing the autopsies. The current work was supported by a Medical Research Council project grant to R.L. and R.J. and in part through Medical Research Council funding of the Alzheimer's Disease Brain Bank.
7. Kay D. Outcome and cause of death in mental disorders of old age: a long-term follow-up of functional and organic psychoses. Ada Psychiatr Scand 1962;38:249-76. 8. Whitehead A, Hunt A. Elderly psychiatric patients: a 5-year prospective study. Psychol Med 1982;12:149-57. 9. Cameron H, McGoogan E. Necropsy: a yardstick for clinical diagnosis. Br Med J 1980;281:985-7. 10. Cameron H, McGoogan E. A prospective study of 1152 hospital autopsies: 2. Analysis of inaccuracies in clinical diagnosis and their significance. J' Pathol 1981; 133:285-300. 11. Medical aspects of death certification: a joint report of the Royal College of Physicians and the Royal College of Pathologists. J R Coll Phys (Lond) 1982;16:205-18. 12. Puxty J, Horan M, Fox R. Necropsies in the elderly. Lancet 1983;i:1262-4. 13. Birkett D. Differentiation between senile and arterosclerotic psychoses. Br J Psychiatry 1972;12O:321-5. 14. Burns A, Reith M, Jacoby R, Levy R. 'How to do it'—obtaining consent for autopsy in Alz1. heimer's disease. Int J Geriatr Psychiatr (in press). 15. Alstrom C. Mortality in mental hospitals with especial regard to tuberculosis. Ada Psychiatr Scand 1942;Suppl. 24. 16. Corsellis J. Mental illness in the aging brain. (Maudsley Monographs No. 9). Oxford: Oxford University Press, 1962. 17. Katzman R. The prevalence and malignancy of Alzheimer disease. Arch Neurol 1976;33:217-8.
