Key Points
Question
What are the age-specific incidence and prevalence of dementia among older US adults with schizophrenia?
Findings
In this cohort study of 8 011 773 individuals in a national Medicare database from 2007 to 2017, at 66 years of age, 27.9% of individuals with schizophrenia also had a dementia diagnosis compared with 1.3% of individuals without a serious mental illness. The prevalence of dementia diagnoses among people with schizophrenia at 66 years of age was similar to the prevalence at 88 years of age for the group without serious mental illness.
Meaning
The findings suggest that further study is needed about the processes and impairments that lead to dementia diagnoses in patients with schizophrenia as well as prevention and treatment strategies.
This cohort study estimates the age-specific incidence and prevalence of dementia diagnoses among older US adults with schizophrenia compared with those in a group without serious mental illness.
Abstract
Importance
People with schizophrenia are at high risk of receiving a diagnosis of dementia. Understanding the magnitude and timing of this increased risk has important implications for practice and policy.
Objective
To estimate the age-specific incidence and prevalence of dementia diagnoses among older US adults with schizophrenia and in a comparison group without serious mental illness (SMI).
Design, Setting, and Participants
This retrospective cohort study used a 50% random national sample of Medicare beneficiaries 66 years or older with fee-for-service plans and Part D prescription drug coverage from January 1, 2007, to December 31, 2017. The cohort with schizophrenia included adults with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and at least 2 outpatient claims or at least 1 inpatient claim for schizophrenia during the qualifying years. The comparison group included adults with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and without a diagnosis of schizophrenia, bipolar disorder, or recurrent major depressive disorder during the qualifying year. Data were analyzed from January 1 to July 31, 2020.
Main Outcomes and Measures
Dementia was defined using the Centers for Medicare & Medicaid Services Chronic Conditions Warehouse diagnosis codes for Alzheimer disease and related disorders or senile dementia. Incident diagnoses were defined by at least 12 consecutive eligible months without a qualifying code before meeting dementia criteria.
Results
The study population of 8 011 773 adults 66 years or older (63.4% women; mean [SD] age, 74.0 [8.2] years) included 74 170 individuals with a diagnosis of schizophrenia (56.6% women) and 7 937 603 without an SMI diagnosis (63.5% women) who contributed 336 814 and 55 499 543 person-years of follow-up, respectively. At 66 years of age, the prevalence of diagnosed dementia was 27.9% (17 640 of 63 287) among individuals with schizophrenia compared with 1.3% (31 295 of 2 389 512) in the group without SMI. By 80 years of age, the prevalence of dementia diagnoses was 70.2% (2011 of 2866) in the group with schizophrenia and 11.3% (242 094 of 2 134 602) in the group without SMI. The annual incidence of dementia diagnoses per 1000 person-years at 66 years of age was 52.5 (95% CI, 50.1-54.9) among individuals with schizophrenia and 4.5 (95% CI, 4.4-4.6) among individuals without SMI and increased to 216.2 (95% CI, 179.9-252.6) and 32.3 (95% CI, 32.0-32.6), respectively, by 80 years of age.
Conclusions and Relevance
In this cohort study, compared with older adults without SMI, those with schizophrenia had increased risk of receiving a diagnosis of dementia across a wide age range, possibly because of cognitive and functional deterioration related to schizophrenia or factors contributing to other types of dementia. High rates of dementia among adults with schizophrenia have implications for the course of illness, treatment, and service use.
Introduction
Schizophrenia is characterized by psychotic symptoms such as hallucinations and delusions, cognitive impairment, and functional deficits. The disorder typically begins in early adulthood and is associated with premature mortality and often with substantial disability.1,2 Dementia is defined by impaired cognition and function. Owing to its effects on behavior and the ability to function independently, dementia markedly affects individuals, families, the health care system, and social welfare programs.3,4 Accumulating evidence from outside the US suggests that people with schizophrenia have a higher than expected risk of dementia.5,6,7,8,9 In the US, a prevalence study of 18 740 Medicare beneficiaries reported that 21% of older adults with schizophrenia (n = 208) were diagnosed with dementia, which translated into an increased odds of approximately 5.8 after controlling for age, sex, race, and educational level.10
The causes and neuropathological basis of dementia among people with schizophrenia are not well understood. For example, in a postmortem study of 100 consecutive brains of middle-aged and older adult patients with schizophrenia,11 72% had moderate or severe cognitive impairment but only 9% met neuropathological criteria for Alzheimer disease (AD). In the largest epidemiologic study on this topic to date, which involved 20 683 individuals with schizophrenia in Denmark,6 a 2-fold excess risk of dementia diagnoses among patients with schizophrenia was not meaningfully diminished after controlling for medical comorbidities, such as diabetes, coronary artery disease, or cerebrovascular diseases, which are risk factors for dementia. Thus, the excess risk of developing dementia among patients with schizophrenia may not be due to an increased risk of AD neuropathology11 or to high prevalence of metabolic problems that are known risk factors for dementia.12,13 Instead, individuals with schizophrenia are hypothesized to have decreased cognitive reserve that, combined with the cognitive decline of aging, puts them at increased risk of crossing a clinical threshold to warrant a dementia diagnosis.14
A recent meta-analysis of 6 studies on rates of dementia among people with schizophrenia,15 all of which were from outside the US, noted a paucity of relevant US research. A better understanding of the incidence and prevalence of dementia among adults with schizophrenia in the US may inform efforts to improve prevention, treatment, and service delivery. For this study, 11 years of US Medicare data were used to examine the age-specific incidence and prevalence of dementia diagnoses among people 66 years or older who had received a diagnosis of schizophrenia and in a comparison group of older adults without serious mental illness (SMI).
Methods
Data Source
This cohort study used data from national Medicare Parts A, B, and D claims from January 1, 2007, to December 31, 2017. Because of Centers for Medicare & Medicaid Services regulations on the size of research data sets, a random sample of approximately 50% of all Part D–enrolled beneficiaries with fee-for-service coverage were included. These beneficiaries had complete claims data on Medicare-covered health services and prescription medications. The institutional review boards of the New York State Psychiatric Institute, New York; Columbia University Department of Psychiatry, New York, New York; and Rutgers University, New Brunswick, New Jersey, approved the study and deemed that informed consent was not required for use of retrospective data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Study Population
The cohort with schizophrenia for the prevalence analysis included all individuals 66 years or older with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and at least 2 outpatient claims or at least 1 inpatient claim for schizophrenia during the qualifying period. The comparison group included all individuals 66 years or older with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and without a diagnosis of schizophrenia, bipolar disorder, or recurrent major depressive disorder during the qualifying year. Individuals with bipolar disorder or recurrent major depressive disorder were excluded from the comparison condition to reduce the possibility of diagnostic overlap with schizophrenia. Because of the 1-year qualifying period and because Medicare eligibility typically begins at 65 years of age, only individuals 66 years or older met the eligibility criteria. For the analyses of incident dementia diagnoses, individuals with any claims with dementia diagnoses or prescription claims for a cholinesterase inhibitor or memantine hydrochloride in the 12-month baseline period were excluded. Race/ethnicity is assigned by self-report in Medicare claims and was included in the study because of previous research showing differences in the prevalence and incidence of dementia among racial/ethnic groups.2
Measurement
Two outpatient codes or 1 inpatient code in any position in the diagnosis list were required to meet the diagnostic criteria for schizophrenia, dementia, and other SMI.16 When individuals met the criteria for schizophrenia, they were considered to retain the condition at all future ages of observation. Dementia was defined using the diagnostic codes used by Centers for Medicare & Medicaid Services Chronic Conditions Warehouse algorithm for AD and related disorders or senile dementia.17 eTable 1 in the Supplement gives the codes from the International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision that were used to define these conditions. Compared with in-person cognitive impairment assessments among older members of the general population, a claims-based definition using this list of diagnostic codes has shown a sensitivity of 85.5%, a specificity of 85.9%, and a κ of 0.70 for the diagnosis of dementia.18 For dementia, 2 outpatient diagnoses had to have been received within a 365-day period. The type of dementia was determined according to diagnostic codes given in the first year, starting with the initial dementia diagnosis, and were categorized as AD, vascular dementia, or unspecified/other. For the incident case analyses, the second observed qualifying code defined the date of diagnosis. For sensitivity analysis, we used a narrower definition of dementia that excluded potentially reversible causes of dementia (eTable 2 in the Supplement gives the narrower list of codes). The broader Centers for Medicare & Medicaid Services Chronic Conditions Warehouse list of diagnoses codes was used in the primary analysis because of its authoritative source and prior validation work.18
Statistical Analysis
Data were analyzed from January 1 to July 31, 2020. The prevalence and incidence of diagnosed dementia were calculated for each year of age for the overall sample and separately by sex. Follow-up for the prevalence analyses began after the 1-year qualifying period was completed and ended with death, end of data availability, or loss of eligibility, whichever came first. For the incidence calculations, follow-up ended with death, diagnosis of dementia, end of data availability, or loss of eligibility, whichever came first. Prevalence rates were also calculated by race/ethnicity and for AD and vascular dementia diagnoses. Stratification by age, sex, and race/ethnicity directly controlled for differences in the demographic distributions between people with schizophrenia and those without SMI. Because individuals diagnosed with dementia were also considered to retain the condition at all future ages, prevalent dementia cases for each year of age included incident cases and all previously identified cases. We provide 95% CIs in the text for selected outcomes to show the significance of findings in these population-based analyses.
To empirically evaluate 1 aspect of the validity of a dementia diagnosis, which is a known risk factor for mortality,19 mortality rates for a given age were compared between the cohorts with schizophrenia alone and with co-occurring dementia and schizophrenia. To examine the possibility that for individuals with schizophrenia, dementia was diagnosed to facilitate admission to nursing homes, rates of nursing home admission within 30 and 90 days of new dementia diagnoses were calculated for the cohort with schizophrenia and the cohort without SMI.
Results
Among the study population of 8 011 773 adults 66 years or older (63.4% women and 36.6% men; mean [SD] age, 74.0 [8.2] years), the group with schizophrenia included 74 170 individuals who met the claims-based diagnostic criteria for schizophrenia. The comparison group included 7 937 603 individuals without SMI. Table 1 provides the sex and race/ethnicity of the 2 groups. The group with schizophrenia included a higher percentage of men (43.4% vs 36.5%) and Black individuals (20.5% vs 7.8%) and a lower percentage of women (56.6% vs 63.5%) and non-Hispanic White individuals (68.6% vs 81.4%).
Table 1. Demographic Characteristics of the Cohort With Schizophrenia and the Cohort Without SMIa.
| Characteristic | Individuals, No. (%) | |
|---|---|---|
| Schizophrenia (n = 74 170) | Without SMI (n = 7 937 603) | |
| Sex | ||
| Male | 32 155 (43.4) | 2 897 000 (36.5) |
| Female | 42 015 (56.6) | 5 040 603 (63.5) |
| Race/ethnicity | ||
| Non-Hispanic White | 50 868 (68.6) | 6 464 119 (81.4) |
| Black | 15 230 (20.5) | 621 835 (7.8) |
| Hispanic | 5686 (7.7) | 478 407 (6.0) |
| Asian or Pacific Islander | 1171 (1.6) | 231 941 (2.9) |
| American Indian or Alaska Native | 418 (0.6) | 32 478 (0.4) |
| Other | 458 (0.6) | 47 945 (0.6) |
| Unknown | 339 (0.5) | 60 878 (0.8) |
Abbreviation: SMI, serious mental illness.
Includes Medicare recipients with schizophrenia and those without SMI from 2007 to 2017.
Prevalence of Dementia Diagnoses
At 66 years of age, the prevalence of dementia diagnoses was 27.9% (17 640 of 63 287) in the group with schizophrenia compared with 1.3% (31 295 of 2 389 512) in the group without SMI (21.5 times higher). By 80 years of age, the prevalence of dementia diagnoses was 70.2% (2011 of 2866) in the group with schizophrenia and 11.3% (242 094 of 2 134 602) in the group without SMI (6.2 times higher) (Table 2 and eFigure 1 in the Supplement). With use of the narrower definition, at 66 years of age, the prevalence of dementia diagnoses was 23.2% (14 660 of 63 287) in the group with schizophrenia compared with 1.0% (24 885 of 2 389 512) in the group without SMI (23.2 times higher). By 80 years of age, with the narrower definition of dementia diagnoses, the prevalence was 61.7% (1768 of 2866) in the group with schizophrenia and 9.6% (204 275 of 2 134 602) in the group without SMI (6.4 times higher) (eTable 3 in the Supplement).
Table 2. Prevalence of Dementia Diagnoses Among Medicare Recipients With Schizophrenia vs Without SMI by Age and Sex.
| Age, y | Cohort with schizophrenia | Cohort without SMI | ||||
|---|---|---|---|---|---|---|
| Dementia diagnoses, No./total No. (%) | Dementia diagnoses, No./total No. (%) | |||||
| All | Male | Female | All | Male | Female | |
| 66 | 17 640/63 287 (27.9) | 8559/28 963 (29.6) | 9081/34 324 (26.5) | 31 295/2 389 512 (1.3) | 15 040/978 590 (1.5) | 16 255/1 410 922 (1.2) |
| 67 | 17 204/54 977 (31.3) | 8170/24 670 (33.1) | 9034/30 307 (29.8) | 44 095/2 558 834 (1.7) | 20 696/1 040 944 (2.0) | 23 399/1 517 890 (1.5) |
| 68 | 15 345/45 262 (33.9) | 7020/19 795 (35.5) | 8325/25 467 (32.7) | 52 919/2 507 420 (2.1) | 23 850/1 012 607 (2.4) | 29 069/1 494 813 (1.9) |
| 69 | 13 417/36 801 (36.5) | 5961/15 730 (37.9) | 7456/21 071 (35.4) | 61 492/2 466 109 (2.5) | 26 939/992 543 (2.7) | 34 553/1 473 566 (2.3) |
| 70 | 11 421/29 302 (39.0) | 4945/12 237 (40.4) | 6476/17 065 (37.9) | 71 259/2 452 488 (2.9) | 30 435/984 477 (3.1) | 40 824/1 468 011 (2.8) |
| 71 | 9357/22 444 (41.7) | 3875/9093 (42.6) | 5482/13 351 (41.1) | 81 987/2 443 326 (3.4) | 34 057/978 226 (3.5) | 47 930/1 465 100 (3.3) |
| 72 | 7634/17 115 (44.6) | 3077/6717 (45.8) | 4557/10 398 (43.8) | 94 158/2 450 901 (3.8) | 38 447/978 083 (3.9) | 55 711/1 472 818 (3.8) |
| 73 | 6150/12 935 (47.5) | 2426/4937 (49.1) | 3724/7998 (46.6) | 110 193/2 494 190 (4.4) | 44 021/990 639 (4.4) | 66 172/1 503 551 (4.4) |
| 74 | 4697/9276 (50.6) | 1770/3391 (52.2) | 2927/5885 (49.7) | 127 176/2 511 907 (5.1) | 49 727/990 084 (5.0) | 77 449/1 521 823 (5.1) |
| 75 | 3327/6136 (54.2) | 1203/2131 (56.5) | 2124/4005 (53.0) | 145 631/2 500 564 (5.8) | 55 657/974 136 (5.7) | 89 975/1 525 428 (5.9) |
| 76 | 2208/3725 (59.3) | 715/1179 (60.6) | 1493/2546 (58.6) | 166 706/2 497 736 (6.7) | 62 357/961 484 (6.5) | 104 349/1 536 252 (6.8) |
| 77 | 2211/3531 (62.6) | 683/1065 (64.1) | 1528/2466 (62.0) | 184 548/2 412 795 (7.6) | 67 386/913 688 (7.4) | 117 162/1 499 107 (7.8) |
| 78 | 2125/3262 (65.1) | 604/927 (65.2) | 1521/2335 (65.1) | 203 698/2 325 789 (8.8) | 72 680/863 898 (8.4) | 131 018/1 461 891 (9.0) |
| 79 | 2056/3048 (67.5) | 558/819 (68.1) | 1498/2229 (67.2) | 223 625/2 232 872 (10.0) | 77 477/812 663 (9.5) | 146 148/1 420 209 (10.3) |
| 80 | 2011/2866 (70.2) | 532/758 (70.2) | 1479/2108 (70.2) | 242 094/2 134 602 (11.3) | 81 368/759 405 (10.7) | 160 726/1 375 197 (11.8) |
| 81 | 1894/2650 (71.5) | 486/674 (72.1) | 1408/1976 (71.3) | 261 205/2 037 312 (12.8) | 84 606/705 840 (12.0) | 176 599/1 331 472 (13.3) |
| 82 | 1851/2489 (74.4) | 459/610 (75.2) | 1392/1879 (74.1) | 279 753/1 936 645 (14.4) | 87 253/651 627 (13.4) | 192 500/1 285 018 (15.0) |
| 83 | 1794/2362 (76.0) | 419/556 (75.4) | 1375/1806 (76.1) | 296 831/1 829 573 (16.2) | 88 896/595 371 (14.9) | 207 935/1 234 202 (16.8) |
| 84 | 1763/2229 (79.1) | 400/514 (77.8) | 1363/1715 (79.5) | 311 978/1 724 490 (18.1) | 89 939/542 727 (16.6) | 222 039/1 181 763 (18.8) |
| 85 | 1643/2040 (80.5) | 354/442 (80.1) | 1289/1598 (80.7) | 324 525/1 618 299 (20.1) | 89 763/493 491 (18.2) | 234 762/1 124 808 (20.9) |
| 86 | 1500/1847 (81.2) | 312/387 (81.3) | 1188/1460 (81.4) | 331 711/1 498 390 (22.1) | 88 221/441 758 (20.0) | 243 490/1 056 632 (23.0) |
| 87 | 1374/1666 (82.5) | 261/317 (82.3) | 1113/1349 (82.5) | 334 669/1 375 574 (24.3) | 85 073/390 414 (21.8) | 249 596/985 160 (25.3) |
| 88 | 1223/1463 (83.6) | 208/251 (82.9) | 1015/1212 (83.8) | 329 283/1 239 661 (26.6) | 80 162/338 050 (23.7) | 249 121/901 611 (27.6) |
| 89 | 1059/1234 (85.8) | 172/203 (84.7) | 887/1031 (86.0) | 316 800/1 096 090 (28.9) | 73 579/286 280 (25.7) | 243 221/809 810 (30.0) |
| 90 | 909/1051 (86.5) | 139/164 (84.8) | 770/887 (86.8) | 296 595/954 827 (31.1) | 65 210/237 619 (27.4) | 231 385/717 208 (32.3) |
| 91 | 794/907 (87.5) | 113/133 (85.0) | 681/774 (88.0) | 271 706/816 719 (33.3) | 56 709/194 255 (29.2) | 214 997/622 464 (34.5) |
| 92 | 636/726 (87.6) | 94/109 (86.2) | 542/617 (87.8) | 243 818/685 909 (35.5) | 48 253/155 750 (31.0) | 195 565/530 159 (36.9) |
| 93 | 498/571 (87.2) | 61/74 (82.4) | 437/497 (87.9) | 213 815/565 331 (37.8) | 40 065/122 338 (32.7) | 173 750/442 993 (39.2) |
| 94 | 391/442 (88.5) | 37/47 (78.7) | 354/395 (89.6) | 182 293/455 682 (40.0) | 32 058/93 492 (34.3) | 150 235/362 190 (41.5) |
| 95 | 311/348 (89.4) | 27/36 (75.0) | 284/312 (91.0) | 150 480/357 766 (42.1) | 24 817/69 163 (35.9) | 125 663/288 603 (43.5) |
Abbreviation: SMI, serious mental illness.
Figure 1 shows the prevalence of dementia diagnoses in the 3 largest racial/ethnic study groups. At 66 years of age, the prevalence of dementia diagnoses among non-Hispanic White individuals was 27.6% (12 021 of 43 483); among Black individuals, 28.8% (3808 of 13 217); and among Hispanic individuals, 28.6% (1290 of 4508). At 80 years of age, the prevalence was 69.3% (1305 of 1883) among non-Hispanic white individuals, 74.6% (405 of 543) among Black individuals, and 67.7% (243 of 359) among Hispanic individuals (Figure 1 and eTable 4 in the Supplement).
Figure 1. Prevalence of Dementia Diagnoses by Age and Race/Ethnicity in Cohorts With Schizophrenia (SZ) and Without Serious Mental Illness (SMI).
eTable 4 in the Supplement includes the number of individuals in each of the 6 groups at each age.
Incidence of Dementia Diagnoses
Among 46 048 adult Medicare beneficiaries 66 years or older who had schizophrenia but not preexisting dementia, the annual incidence of dementia diagnoses per 1000 person-years increased from 52.5 (95% CI, 50.1-54.9) for adults aged 66 years to 216.2 (95% CI, 179.9-252.6) for adults aged 80 years. Among 7 300 048 adults without SMI and preexisting dementia, the corresponding increase per 1000 person-years was from 4.5 (95% CI, 4.4-4.6) for adults aged 66 years to 32.3 (95% CI, 32.0-32.6) for adults aged 80 years (Figure 2 and Table 3).
Figure 2. Incidence of Dementia Diagnoses by Age in Cohorts With Schizophrenia (SZ) and Without Serious Mental Illness (SMI).
Table 3. Incidence of Dementia Diagnoses Among Medicare Recipients With Schizophrenia vs Recipients Without SMI by Age and Sex.
| Age, y | Cohort with schizophrenia | Cohort without SMI | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All | Male | Female | All | Male | Female | |||||||||
| No. of patients | Incidence, per 1000 person-years (95% CI) | No. of patients | Incidence, per 1000 person-years (95% CI) | No. of patients | Incidence, per 1000 person-years (95% CI) | No. of patients | Incidence, per 1000 person-years (95% CI) | No. of patients | Incidence, per 1000 person-years (95% CI) | No. of patients | Incidence, per 1000 person-years (95% CI) | |||
| Total | New dementia diagnoses | Total | New dementia diagnoses | |||||||||||
| 66 | 41 335 | 1819 | 52.5 (50.1-54.9) | 18 435 | 52.4 (48.8-56.0) | 22 900 | 52.6 (49.3-55.8) | 2 341 437 | 9919 | 4.5 (4.4-4.6) | 956 593 | 5.2 (5.0-5.3) | 1 384 844 | 4.0 (3.9-4.1) |
| 67 | 31 977 | 1650 | 60.4 (57.5-63.4) | 13 847 | 61.2 (56.7-65.7) | 18 130 | 59.9 (56.0-63.7) | 2 359 510 | 12 282 | 5.8 (5.6-5.9) | 952 055 | 6.5 (6.3-6.7) | 1 407 455 | 5.2 (5.1-5.4) |
| 68 | 23 851 | 1334 | 66.0 (62.4-69.5) | 10 130 | 70.6 (65.0-76.3) | 13 721 | 62.6 (58.0-67.1) | 2 222 272 | 13 064 | 6.5 (6.4-6.6) | 888 113 | 7.1 (6.9-7.2) | 1 334 159 | 6.1 (5.9-6.2) |
| 69 | 17 640 | 1027 | 68.8 (64.6-73.0) | 7324 | 70.4 (63.7-77.0) | 10 316 | 67.7 (62.2-73.1) | 2 115 877 | 14 706 | 7.6 (7.5-7.7) | 841 652 | 8.2 (8.0-8.4) | 1 274 225 | 7.2 (7.1-7.4) |
| 70 | 13 008 | 807 | 74.8 (69.6-80.0) | 5278 | 74.4 (66.3-82.5) | 7730 | 75.1 (68.4-81.8) | 2 054 458 | 16 562 | 8.8 (8.6-8.9) | 814 722 | 9.1 (8.8-9.3) | 1 239 736 | 8.6 (8.4-8.8) |
| 71 | 9234 | 647 | 86.3 (79.7-93.0) | 3658 | 80.8 (70.5-91.1) | 5576 | 89.9 (81.2-98.6) | 2 000 219 | 17 968 | 9.8 (9.6-9.9) | 790 940 | 10.0 (9.8-10.2) | 1 209 279 | 9.6 (9.4-9.8) |
| 72 | 6553 | 530 | 100.2 (91.7-108.8) | 2511 | 100.9 (87.0-114.8) | 4042 | 99.8 (89.5-115.6) | 1 966 332 | 20 682 | 11.3 (11.1-11.4) | 775 256 | 11.6 (11.4-11.9) | 1 191 076 | 11.0 (10.8-11.2) |
| 73 | 4601 | 368 | 101.6 (91.2-117.9) | 1679 | 99.9 (82.8-117.0) | 2922 | 102.5 (89.5-115.6) | 1 963 967 | 23 467 | 12.8 (12.6-13.0) | 770 929 | 12.9 (12.7-13.2) | 1 193 038 | 12.7 (12.5-12.9) |
| 74 | 3141 | 250 | 104.9 (91.9-117.9) | 1090 | 112.8 (89.6-135.9) | 2051 | 100.8 (85.2-116.5) | 1 945 199 | 26 721 | 14.7 (14.5-14.9) | 758 057 | 14.9 (14.7-15.2) | 1 187 142 | 14.6 (14.4-14.8) |
| 75 | 2127 | 179 | 116.9 (99.8-134.0) | 670 | 125.3 (93.0-157.5) | 1457 | 113.4 (93.2-133.6) | 1 904 886 | 30 113 | 16.9 (16.8-17.1) | 733 735 | 17.0 (16.7-17.3) | 1 171 151 | 16.9 (16.7-17.1) |
| 76 | 1347 | 158 | 143.5 (121.1-165.9) | 392 | 118.2 (80.1-156.3) | 955 | 153.6 (126.2-180.9) | 1 876 256 | 33 429 | 19.3 (19.1-19.6) | 712 871 | 19.6 (19.2-19.9) | 1 163 385 | 19.2 (18.9-19.5) |
| 77 | 1195 | 154 | 162.3 (136.6-187.9) | 351 | 180.8 (130.2-231.4) | 844 | 155.1 (125.4-184.8) | 1 799 011 | 36 773 | 22.3 (22.0-22.5) | 672 315 | 22.6 (22.2-23.0) | 1 126 696 | 22.1 (21.8-22.4) |
| 78 | 1027 | 124 | 151.6 (124.9-178.3) | 290 | 120.7 (76.0-165.4) | 737 | 163.8 (131.1-196.6) | 1 723 060 | 39 770 | 25.2 (24.9-25.4) | 632 054 | 25.2 (24.8-25.6) | 1 091 006 | 25.2 (24.9-25.5) |
| 79 | 905 | 114 | 159.0 (129.8-188.2) | 250 | 205.0 (142.2-267.8) | 655 | 141.2 (10.8.8-173.6) | 1 639 281 | 42 677 | 28.5 (28.3-28.8) | 589 900 | 28.5 (28.1-29.0) | 1 049 381 | 28.6 (28.2-28.9) |
| 80 | 798 | 136 | 216.2 (179.9-252.6) | 219 | 241.2 (167.4-315.0) | 579 | 207.0 (165.4-248.6) | 1 552 326 | 45 581 | 32.3 (32.0-32.6) | 546 595 | 32.0 (31.5-32.5) | 1 005 731 | 32.4 (32.0-32.8) |
| 81 | 683 | 86 | 161.7 (127.5-195.8) | 176 | 175.2 (105.1-245.3) | 507 | 157.4 (118.2-196.5) | 1 464 288 | 48 681 | 36.5 (36.2-36.9) | 502 695 | 36.1 (35.6-36.7) | 961 593 | 36.7 (36.3-37.1) |
| 82 | 610 | 93 | 196.2 (156.3-236.1) | 146 | 220.2 (132.1-308.3) | 464 | 189.0 (144.4-233.6) | 1 371 758 | 51 388 | 41.3 (41.0-41.7) | 457 688 | 40.7 (40.0-41.3) | 914 070 | 41.6 (41.2-42.1) |
| 83 | 540 | 104 | 254.9 (205.9-303.9) | 125 | 247.3 (146.2-348.4) | 415 | 257.1 (201.1-313.1) | 1 273 856 | 53 614 | 46.6 (46.2-47.0) | 411 327 | 45.3 (44.7-46.0) | 862 529 | 47.1 (46.6-47.6) |
| 84 | 429 | 68 | 204.2 (155.7-252.7) | 94 | 114.3 (35.1-193.5) | 335 | 228.1 (170.4-285.9) | 1 178 492 | 55 594 | 52.2 (51.8-52.7) | 368 864 | 51.4 (50.6-52.2) | 809 628 | 52.6 (52.1-53.1) |
| 85 | 360 | 49 | 173.8 (125.1-222.4) | 76 | 133.3 (40.9-225.7) | 284 | 183.9 (127.6-240.1) | 1 080 843 | 56 635 | 58.4 (57.9-58.9) | 328 644 | 57.6 (56.7-58.5) | 752 199 | 58.7 (58.1-59.3) |
| 86 | 328 | 48 | 191.2 (137.1-245.3) | 74 | 211.5 (86.5-336.5) | 254 | 185.9 (126.0-245.8) | 975 933 | 56 321 | 64.7 (64.1-65.2) | 287 628 | 62.6 (61.6-63.6) | 688 305 | 65.5 (64.9-66.1) |
| 87 | 274 | 45 | 206.4 (146.1-266.7) | 54 | 190.5 (58.5-322.5) | 220 | 210.2 (142.5-278.0) | 873 552 | 56 454 | 73.0 (72.4-73.6) | 248 710 | 71.7 (70.6-72.9) | 624 842 | 73.5 (72.8-74.2) |
| 88 | 237 | 52 | 292.1 (212.7-371.5) | 48 | 375.0 (162.8-587.2) | 189 | 274.0 (189.1-358.9) | 764 724 | 53 975 | 80.2 (79.6-80.9) | 209 994 | 80.1 (78.8-81.4) | 554 730 | 80.3 (79.5-81.1) |
| 89 | 186 | 44 | 312.1 (219.9-404.3) | 32 | 333.3 (102.3-564.3) | 154 | 310.3 (209.0-411.7) | 654 331 | 50 279 | 88.1 (87.4-88.9) | 172 722 | 85.6 (84.1-87.1) | 481 609 | 89.0 (88.1-89.9) |
| 90 | 145 | 31 | 292.5 (189.5-395.4) | 24 | 375.0 (74.9-675.1) | 121 | 277.8 (168.9-386.7) | 551 617 | 45 206 | 94.7 (93.9-95.6) | 139 669 | 92.0 (90.2-93.7) | 411 948 | 95.7 (94.7-96.7) |
| 91 | 108 | 26 | 333.3 (205.2-461.5) | 11 | 333.3 (0-710.5) | 97 | 333.3 (197.1-469.6) | 456 476 | 41 073 | 104.9 (103.9-105.9) | 111 102 | 103.0 (101.0-115.1) | 345 374 | 105.5 (104.4-106.7) |
| 92 | 85 | 13 | NRa | NRa | 142.9 (0-422.9) | 75 | 206.9 (89.8-324.0) | 369 869 | 36 478 | 116.2 (115.0-117.4) | 86 466 | 112.8 (110.3-115.2) | 283 403 | 117.2 (115.9-118.6) |
| 93 | 75 | 21 | NRa | NRa | 400.0 (0-954.4) | 67 | 413.0 (227.3-598.8) | 293 622 | 31 195 | 126.7 (125.3-128.1) | 65 991 | 123.8 (120.8-126.8) | 227 631 | 127.5 (125.9-129.1) |
| 94 | 53 | 13 | NRa | NRa | 200.0 (0-592.0) | 47 | 363.6 (157.9-569.4) | 227 275 | 25 773 | 136.7 (135.1-138.4) | 48 901 | 134.3 (130.7-137.9) | 178 374 | 137.4 (135.5-139.3) |
| ≥95 | 99 | 24 | 338.0 (202.8-473.3) | 25 | 200.0 (4.0-396.0) | 74 | 392.2 (220.3-564.0) | 563 080 | 73 252 | 162.9 (161.8-164.1) | 104 099 | 155.3 (152.6-158.0) | 458 981 | 164.6 (163.3-165.9) |
Abbreviations: NR, not reported; SMI, serious mental illness.
Users of data from the Centers for Medicare & Medicaid Services may not display cells of 10 or less.
Using the narrower set of dementia diagnoses, the annual incidence of dementia diagnoses per 1000 person-years increased from 46.6 (95% CI, 44.4-48.8) for adults aged 66 years to 180.3 (95% CI, 150.5-210.1) for adults aged 80 years. Among 7 390 157 adults without SMI and preexisting dementia, the corresponding increase was from 3.6 (95% CI, 3.5-3.7) for adults aged 66 years to 28.1 (95% CI, 27.8-28.4) for adults aged 80 years (eTable 5 in the Supplement).
Dementia Types
At 66 years of age, 5.0% (3147 of 63 287) of individuals with schizophrenia had a diagnosis of vascular dementia compared with 0.2% (4476 of 2 389 512) in the non-SMI comparison group. By 80 years of age, the prevalence of vascular dementia diagnoses was 15.6% (446 of 2866) in the group with schizophrenia and 1.5% (32 141 of 2 134 602) in the group without SMI. The prevalence of AD diagnoses at 66 years of age was 8.2% (5179 of 63 287) in the group with schizophrenia and 0.4% (8677 of 2 389 512) in the group without SMI. By 80 years of age, the prevalence of AD diagnoses was 37.2% (1065 of 2866) in the group with schizophrenia and 5.1% (108 836 of 2 134 602) in the comparison group (eTables 6 and 7 in the Supplement).
Nursing Home Residence and Dementia Diagnoses
In the group with schizophrenia, 29.4% (2948 of 10 014) first received a dementia diagnosis while in a nursing home compared with 16.5% (184 872 of 1 119 632) in the group without SMI. Among people who were not in a nursing home at the time of their first diagnosis of dementia, 25.2% in the group with schizophrenia (1779 of 7066) and in the group without SMI (235 817 of 934 760) were admitted to a nursing home within 30 days of dementia diagnosis. Within 90 days of dementia diagnosis, this rate increased to 30.8% (2178 of 7066) in the group with schizophrenia and 28.7% (268 708 of 934 760) in the group without SMI (eTable 8 in the Supplement).
Mortality
At 66 years of age, the mortality rate per 1000 person-years was 125.2 (95% CI, 119.0-131.5) for persons with schizophrenia and dementia diagnoses compared with 60.8 (95% CI, 58.2-63.5) for persons with schizophrenia without a dementia diagnosis. At 80 years of age, the corresponding mortality rates were 199.7 (95% CI, 177.4-222.1) and 172.7 (95% CI, 139.7-205.7) (eTable 9 and eFigure 2 in the Supplement).
In the group without SMI, the annual mortality rate at 66 years of age per 1000 person-years was 138.4 (95% CI, 133.5-143.2) for persons with dementia diagnoses and 17.8 (95% CI, 17.6-18.0) for persons without a dementia diagnosis. At 80 years of age, the corresponding mortality rates were 181.9 (95% CI, 179.9-183.9) and 45.9 (95% CI, 45.6-46.2) (eTable 9 and eFigure 2 in the Supplement).
Discussion
This retrospective longitudinal cohort study found a markedly elevated rate of dementia diagnoses among US Medicare beneficiaries 66 years or older who had schizophrenia compared with beneficiaries who did not have an SMI diagnosis. Age-specific analyses revealed that people with schizophrenia compared with those without SMI received dementia diagnoses at younger ages. Notably, the prevalence of diagnosed dementia among people with schizophrenia at 66 years of age was similar to the prevalence of diagnosed dementia at 88 years of age for the group without SMI. Increased incidence of dementia diagnoses in the group with schizophrenia showed the greatest increase at younger ages but was apparent across the older adult life span. Elevated rates of dementia diagnoses among older adults with schizophrenia were present in men, women, and all racial/ethnic groups. In the population with schizophrenia, which is known to be associated with a high risk of premature death,2 dementia diagnoses were associated with an additional increased risk of mortality, especially among those who were younger.
The elevated risk of dementia diagnoses among people with schizophrenia found in the present study is consistent with results from other countries5,6,7,8,9 and 1 earlier US report.10 Compared with the findings from a study of the long-term risk of dementia in persons with schizophrenia in Denmark,6 the rates of dementia diagnoses in the US were higher. One possible contributor to this difference is the substantially higher rates of dementia in the general population in the US compared with Denmark.20 Prior work in the US10 included all Medicare recipients 65 years or older and found an adjusted odds ratio of 5.8 for a diagnosis of dementia among individuals diagnosed with schizophrenia. This overall odds ratio is consistent with the results of the present study, but the prior investigation did not examine age-specific prevalence. Because dementia was diagnosed at younger ages in the group with schizophrenia than in the group without SMI, the magnitude of the increased incidence and prevalence was larger among people in their late 60s than among older people.
The causes of increased rates of dementia among people with schizophrenia are not fully understood. Factors associated with dementia, such as cardiovascular disease, hyperlipidemia, smoking, and substance use disorders, are especially common among individuals with schizophrenia.12,13 Prior research, however, suggests that the risk of dementia among people with schizophrenia is largely independent of substance use disorders or comorbid medical conditions, although lower adherence to treatments prescribed for hypertension, diabetes, and vascular disease may contribute to the risk.6 Decreased cognitive reserve associated with schizophrenia and the cumulative effect of behavioral and metabolic factors associated with dementia that are common in individuals with schizophrenia may accelerate the rate at which individuals in this group cross a cognitive functioning threshold warranting a clinical dementia diagnosis.
Individuals with schizophrenia commonly take several psychotropic medications during the course of their lifetime. Whether and how these affect the onset and course of dementia need further investigation. For example, benzodiazepines, which are commonly prescribed to people with schizophrenia,21 are associated with worsened cognition and may be associated with increased risk of dementia in the general population.22,23,24 For individuals with schizophrenia, antipsychotics are associated with improved clinical outcomes25 and lower mortality rates,26 but effects on other and longer-term outcomes are less clear.27 Antipsychotics are labeled with a cautionary warning for use in individuals with dementia because of an increased risk of death. Investigations of the effects of antipsychotic treatment on mortality and other key clinical outcomes among older adults with schizophrenia and dementia are urgently needed.
The current population-based analyses did not attempt to control for comorbidities that might contribute to the differences in risk of incident dementia diagnosis. Instead, results were stratified by sex and race/ethnicity to assess outcomes in demographic groups. This approach aligned with our primary goal of defining the real-world clinical burden of dementia diagnoses in individuals with schizophrenia.
The high proportion of older adults with schizophrenia who had dementia diagnoses in Medicare claims may have been attributable in part to factors that are not neuropathological. For example, life events such as the death of a spouse or other caregivers that necessitate skilled nursing care or other assistance may be associated with a lower threshold for clinical dementia diagnoses. In these situations, dementia diagnoses may facilitate nursing home admissions because of the stringent federal eligibility criteria for placing adults with schizophrenia or other mental illnesses in long-term nursing facilities.28 However, the present analyses did not reveal a large excess of nursing home admissions within 30 or 90 days of the first dementia diagnosis in the group with schizophrenia.
As expected, dementia diagnoses were associated with higher mortality rates, although this association among people with schizophrenia was smaller than in the comparison population without SMI. One reason for this attenuation may be that, among people with schizophrenia, the mortality rate due to other causes was high and any additional effects of dementia were therefore modest. As suggested by postmortem research,11 dementia diagnosed in people with schizophrenia may be less severe or neuroanatomically different from dementia diagnosed in the general population and may reflect progression of or accelerated aging associated with schizophrenia.29
Cognitive and functional decline that surpasses the threshold for a dementia diagnosis in individuals with schizophrenia brings serious clinical challenges, including proper assessment and management. For example, the US Food and Drug Administration’s black box warning of increased risk of death when antipsychotics are used by people with dementia30 directly contradicts recommendations for first-line treatment of schizophrenia. In the absence of evidence-based guidance on pharmacologic treatment strategies, an innovative approach is a cognitive health toolkit that provides materials for assessment and service planning.31 Additional research is needed to determine evidence-based pharmacotherapies for individuals with schizophrenia who develop dementia.
Much remains to be learned about the onset, course, and management of schizophrenia in patients with comorbid dementia. It is not known why some adults but not others with schizophrenia undergo progressive cognitive decline decades before the usual onset of dementia in the general population.32 Identification of modifiable risk factors, possibly including anticholinergic medications,33 inadequately treated psychosis, and comorbid medical conditions such as hypertension and diabetes, may help focus prevention efforts. Further investigation is also needed of the clinical assessment of dementia in patients with schizophrenia, particularly broad neuropsychological assessment that covers the characteristic cognitive deficits of both schizophrenia and dementia and the evaluation of different medication classes for treatment and the course of illness in people with schizophrenia and dementia. Given the large number of affected individuals, high priority should be given to research in these areas that will aid in the development of clinical practice guidelines for the prevention, assessment, and management of dementia in adults with schizophrenia.
Limitations
A limitation of large-scale, claims-based research of neuropsychiatric conditions is that the research relies on clinical diagnoses that cannot be confirmed by clinical interview or pathologic results. The validity of claims-based diagnoses of dementia used in these analyses has been demonstrated in the general population, and age-specific prevalence estimates of diagnosed dementia from the cohort without SMI closely tracked population estimates from prior investigations using Medicare data10 and from other sources.34 However, this algorithm has not been validated for patients with schizophrenia.
Because cognitive impairment is a core component of schizophrenia, deciding when an individual’s cognitive functioning warrants a dementia diagnosis is a clinical challenge that has been the subject of considerable research and commentary.35 Factors contributing to diagnostic challenges include preexisting cognitive impairment and difficulties conducting comprehensive neuropsychological testing in individuals with schizophrenia.
Analyses using Medicare claims may reveal increased rates of dementia diagnoses compared with actual rates of confirmed dementia. The list of diagnosis codes included in the validated dementia algorithm in the primary analyses included some potentially reversible causes of cognitive impairment. Clinically it is important to identify and address these causes. However, use of a narrower set of dementia diagnoses in sensitivity analyses revealed reduced dementia diagnoses rates of only about 20%, with proportionate reductions in the group with schizophrenia and the group without SMI; the prevalence of dementia diagnoses among individuals with schizophrenia remained more than 20 times higher than that in the group without SMI at 66 years of age.
Conclusions
In this cohort study, the prevalence and incidence of dementia diagnoses was markedly elevated among older adults with schizophrenia compared with individuals without an SMI. Approximately 28% of the group with schizophrenia had received a diagnosis of dementia before 66 years of age, indicating early-onset dementia. The implications of this high rate of comorbidity are substantial for families and for the service system, which must provide high levels of care for individuals with a combination of disabling conditions and uncertain treatment pathways.
eTable 1. CMS Chronic Conditions Warehouse Diagnostic Codes for Alzheimer Disease and Related Disorders or Senile Dementia
eTable 2. Narrower List of Dementia Codes for Sensitivity Analysis
eTable 3. Prevalence of Dementia Diagnoses Using Narrower Definition of ADRD
eTable 4. Prevalence of Dementia Diagnoses by Race/Ethnicity and Sex by SZ and Non-SMI
eTable 5. Incidence of Dementia Diagnoses With Narrower Dementia Definition
eTable 6. Prevalence of Vascular Dementia by Age
eTable 7. Prevalence of Alzheimer Disease in Schizophrenia Patients vs Non-SMI Patients
eTable 8. Timing of Dementia Diagnoses Relative to Nursing Home Admission
eTable 9. Mortality SZ and Non-SMI With and Without ADRD:
Deaths per 1000 Person-Years
eFigure 1. Prevalence of Dementia Diagnoses by Age in Schizophrenia and Non-SMI Cohorts
eFigure 2. Incidence of Mortality in Schizophrenia and Non-SMI Cohorts
With and Without ADRD Diagnoses
References
- 1.World Health Organization . The Global Burden of Disease. WHO Press; 2008. [Google Scholar]
- 2.Olfson M, Gerhard T, Huang C, Crystal S, Stroup TS. Premature mortality among adults with schizophrenia in the United States. JAMA Psychiatry. 2015;72(12):1172-1181. doi: 10.1001/jamapsychiatry.2015.1737 [DOI] [PubMed] [Google Scholar]
- 3.Alzheimer’s Association . 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459-509. doi: 10.1016/j.jalz.2016.03.001 [DOI] [PubMed] [Google Scholar]
- 4.Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(8):a006239. doi: 10.1101/cshperspect.a006239 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ku H, Lee EK, Lee KU, Lee MY, Kwon JW. Higher prevalence of dementia in patients with schizophrenia: a nationwide population-based study. Asia Pac Psychiatry. 2016;8(2):145-153. doi: 10.1111/appy.12239 [DOI] [PubMed] [Google Scholar]
- 6.Ribe AR, Laursen TM, Charles M, et al. Long-term risk of dementia in persons with schizophrenia: a Danish population-based cohort study. JAMA Psychiatry. 2015;72(11):1095-1101. doi: 10.1001/jamapsychiatry.2015.1546 [DOI] [PubMed] [Google Scholar]
- 7.Kessing LV, Olsen EW, Mortensen PB, Andersen PK. Dementia in affective disorder: a case-register study. Acta Psychiatr Scand. 1999;100(3):176-185. doi: 10.1111/j.1600-0447.1999.tb10843.x [DOI] [PubMed] [Google Scholar]
- 8.Zilkens RR, Bruce DG, Duke J, Spilsbury K, Semmens JB. Severe psychiatric disorders in mid-life and risk of dementia in late-life (age 65-84 years): a population based case-control study. Curr Alzheimer Res. 2014;11(7):681-693. doi: 10.2174/1567205011666140812115004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Lin CE, Chung CH, Chen LF, Chi MJ. Increased risk of dementia in patients with schizophrenia: a population-based cohort study in Taiwan. Eur Psychiatry. 2018;53:7-16. doi: 10.1016/j.eurpsy.2018.05.005 [DOI] [PubMed] [Google Scholar]
- 10.Brown MT, Wolf DA. Estimating the prevalence of serious mental illness and dementia diagnoses among Medicare beneficiaries in the Health and Retirement Survey. Res Aging. 2018;40(7):668-686. doi: 10.1177/0164027517728554 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Purohit DP, Perl DP, Haroutunian V, Powchik P, Davidson M, Davis KL. Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases. Arch Gen Psychiatry. 1998;55(3):205-211. doi: 10.1001/archpsyc.55.3.205 [DOI] [PubMed] [Google Scholar]
- 12.McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005;80(1):19-32. doi: 10.1016/j.schres.2005.07.014 [DOI] [PubMed] [Google Scholar]
- 13.Subramaniam M, Lam M, Guo ME, et al. Body mass index, obesity, and psychopathology in patients with schizophrenia. J Clin Psychopharmacol. 2014;34(1):40-46. doi: 10.1097/JCP.0000000000000058 [DOI] [PubMed] [Google Scholar]
- 14.Kirkpatrick B, Messias E, Harvey PD, Fernandez-Egea E, Bowie CR. Is schizophrenia a syndrome of accelerated aging? Schizophr Bull. 2008;34(6):1024-1032. doi: 10.1093/schbul/sbm140 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Cai L, Huang J. Schizophrenia and risk of dementia: a meta-analysis study. Neuropsychiatr Dis Treat. 2018;14:2047-2055. doi: 10.2147/NDT.S172933 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Lurie N, Popkin M, Dysken M, Moscovice I, Finch M. Accuracy of diagnoses of schizophrenia in Medicaid claims. Hosp Community Psychiatry. 1992;43(1):69-71. doi: 10.1176/ps.43.1.69 [DOI] [PubMed] [Google Scholar]
- 17.Chronic Conditions Data Warehouse. Condition categories. Accessed August 21, 2020. https://www2.ccwdata.org/web/guest/condition-categories
- 18.Taylor DH Jr, Fillenbaum GG, Ezell ME. The accuracy of Medicare claims data in identifying Alzheimer’s disease. J Clin Epidemiol. 2002;55(9):929-937. doi: 10.1016/S0895-4356(02)00452-3 [DOI] [PubMed] [Google Scholar]
- 19.Fitzpatrick AL, Kuller LH, Lopez OL, Kawas CH, Jagust W. Survival following dementia onset: Alzheimer’s disease and vascular dementia. J Neurol Sci. 2005;229-230:43-49. doi: 10.1016/j.jns.2004.11.022 [DOI] [PubMed] [Google Scholar]
- 20.Ferri CP, Prince M, Brayne C, et al. ; Alzheimer’s Disease International . Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112-2117. doi: 10.1016/S0140-6736(05)67889-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Stroup TS, Gerhard T, Crystal S, et al. Psychotropic medication use among adults with schizophrenia and schizoaffective disorder in the United States. Psychiatr Serv. 2018;69(5):605-608. doi: 10.1176/appi.ps.201700356 [DOI] [PubMed] [Google Scholar]
- 22.Billioti de Gage S, Pariente A, Bégaud B. Is there really a link between benzodiazepine use and the risk of dementia? Expert Opin Drug Saf. 2015;14(5):733-747. doi: 10.1517/14740338.2015.1014796 [DOI] [PubMed] [Google Scholar]
- 23.Zhong G, Wang Y, Zhang Y, Zhao Y. Association between benzodiazepine use and dementia: a meta-analysis. PLoS One. 2015;10(5):e0127836. doi: 10.1371/journal.pone.0127836 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Islam MM, Iqbal U, Walther B, et al. Benzodiazepine use and risk of dementia in the elderly population: a systematic review and meta-analysis. Neuroepidemiology. 2016;47(3-4):181-191. doi: 10.1159/000454881 [DOI] [PubMed] [Google Scholar]
- 25.Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379(9831):2063-2071. doi: 10.1016/S0140-6736(12)60239-6 [DOI] [PubMed] [Google Scholar]
- 26.Torniainen M, Mittendorfer-Rutz E, Tanskanen A, et al. Antipsychotic treatment and mortality in schizophrenia. Schizophr Bull. 2015;41(3):656-663. doi: 10.1093/schbul/sbu164 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry. 2013;70(9):913-920. doi: 10.1001/jamapsychiatry.2013.19 [DOI] [PubMed] [Google Scholar]
- 28.Linkins K, Robinson G, Karp J, Cooper S, Liu J, Bush S. Screening for mental illness in nursing facility applications: understanding federal requirements. Policy Report. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration publication 01-3542. Published July 2001. Accessed February 4, 2021. https://secure.ce-credit.com/articles/100898/CMHS2a.pdf
- 29.Harvey PD, Rosenthal JB. Cognitive and functional deficits in people with schizophrenia: evidence for accelerated or exaggerated aging? Schizophr Res. 2018;196:14-21. doi: 10.1016/j.schres.2017.05.009 [DOI] [PubMed] [Google Scholar]
- 30.Janssen Pharmaceutical Companies . Risperdal (risperidone) [package insert]. US Food and Drug Administration website. Revised January 2019. Accessed February 4, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020272s082,020588s070,021444s056lbl.pdf
- 31.Saperstein AM, Medalia A, Malinovsky I, Bello I, Dixon LB. Toolkit for assessing and addressing cognitive health in early psychosis: evaluation of feasibility and utility in a coordinated specialty care setting. Early Interv Psychiatry. Published online November 12, 2020. doi: 10.1111/eip.13070 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Gupta S, Kulhara P. What is schizophrenia: a neurodevelopmental or neurodegenerative disorder or a combination of both? a critical analysis. Indian J Psychiatry. 2010;52(1):21-27. doi: 10.4103/0019-5545.58891 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Tsoutsoulas C, Mulsant BH, Kumar S, et al. Anticholinergic burden and cognition in older patients with schizophrenia. J Clin Psychiatry. 2017;78(9):e1284-e1290. doi: 10.4088/JCP.17m11523 [DOI] [PubMed] [Google Scholar]
- 34.Corrada MM, Brookmeyer R, Berlau D, Paganini-Hill A, Kawas CH. Prevalence of dementia after age 90: results from the 90+ study. Neurology. 2008;71(5):337-343. doi: 10.1212/01.wnl.0000310773.65918.cd [DOI] [PubMed] [Google Scholar]
- 35.Lyketsos CG, Peters ME. Dementia in patients with schizophrenia: evidence for heterogeneity. JAMA Psychiatry. 2015;72(11):1075-1076. doi: 10.1001/jamapsychiatry.2015.1745 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. CMS Chronic Conditions Warehouse Diagnostic Codes for Alzheimer Disease and Related Disorders or Senile Dementia
eTable 2. Narrower List of Dementia Codes for Sensitivity Analysis
eTable 3. Prevalence of Dementia Diagnoses Using Narrower Definition of ADRD
eTable 4. Prevalence of Dementia Diagnoses by Race/Ethnicity and Sex by SZ and Non-SMI
eTable 5. Incidence of Dementia Diagnoses With Narrower Dementia Definition
eTable 6. Prevalence of Vascular Dementia by Age
eTable 7. Prevalence of Alzheimer Disease in Schizophrenia Patients vs Non-SMI Patients
eTable 8. Timing of Dementia Diagnoses Relative to Nursing Home Admission
eTable 9. Mortality SZ and Non-SMI With and Without ADRD:
Deaths per 1000 Person-Years
eFigure 1. Prevalence of Dementia Diagnoses by Age in Schizophrenia and Non-SMI Cohorts
eFigure 2. Incidence of Mortality in Schizophrenia and Non-SMI Cohorts
With and Without ADRD Diagnoses