The study design was a nested case-control study (Fig. 1). The study subjects were over 50 years old with newly diagnosed Parkinson’s disease (ICD-9-CM = 332) at least twice in outpatient department or one admission from year 2000 to 2010 (N = 7990). Patients diagnosed of dementia (ICD-9-CM = 290.0-290.4, 294.1, 331.0-331.2) before the diagnosis of Parkinson’s disease were excluded (N = 6211). The patients in the dementia group were newly diagnosed of dementia at least twice in outpatient department or one admission after diagnosis of Parkinson’s disease and at least 3 years apart (N = 1299). Non-dementia group were patients not diagnosed of dementia after the diagnosis of Parkinson’s disease and were matched in a 1:1 ratio with respect to age (± 2 years), gender and the diagnosed year of Parkinson’s disease with patients in the dementia group (N = 981).
Demographic characteristics of dementia and non-dementia in cohort of Parkinson’s disease were shown in Table 1.
Table 1
Demographic characteristics of dementia and non-dementia in cohort of Parkinson’s disease
| Dementia (N = 981) | | Non-dementia (N = 981) | |
| n | % | | n | % | p-value |
Age | | | | 0.226 |
50–64 | 42 | 4.3 | | 42 | 4.3 | |
65–79 | 515 | 52.5 | | 552 | 56.3 | |
≥ 80 | 424 | 43.2 | | 387 | 39.4 | |
Mean ± SD | 78.3 ± 7.3 | | 77.8 ± 7.1 | 0.097 |
Gender | | | | | | 1 |
Female | 517 | 52.7 | | 517 | 52.7 | |
Male | 464 | 47.3 | | 464 | 47.3 | |
Hypertension | 714 | 72.8 | | 682 | 69.5 | 0.111 |
Hyperlipidemia | 223 | 22.7 | | 280 | 28.5 | 0.003 |
Chronic liver disease | 110 | 11.2 | | 103 | 10.5 | 0.611 |
Chronic kidney disease | 90 | 9.2 | | 49 | 5.0 | < 0.001 |
Diabetes | 316 | 32.2 | | 297 | 30.3 | 0.355 |
COPD | 260 | 26.5 | | 169 | 17.2 | < 0.001 |
Autoimmune disease | 22 | 2.2 | | 16 | 1.6 | 0.326 |
Cardiovascular disease | 282 | 28.7 | | 280 | 28.5 | 0.920 |
Stroke | 496 | 50.6 | | 349 | 35.6 | < 0.001 |
Gout | 104 | 10.6 | | 112 | 11.4 | 0.564 |
Medication usage TCM | 295 | 30.1 | | 377 | 38.4 | < 0.001 |
Warfarin | 35 | 3.6 | | 28 | 2.9 | 0.370 |
Statin | 209 | 21.3 | | 289 | 29.5 | < 0.001 |
Follow-up period (years) | 5.2 ± 2.3 | | 5.2 ± 2.2 | 0.953 |
COPD: Chronic obstructive pulmonary disease.; TCM: Traditional Chinese Medicine |
In the univariate analysis, case and control patients were similar with regard to age, sex, hypertension, chronic liver disease, diabetes, autoimmune disease, cardiovascular disease, gout, warfarin usage and follow-up periods. A history of chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and stroke were more associated with dementia group. A history of TCM usage, statin usage and hyperlipidemia were more associated with non-dementia group (Table 1).
Certain kinds of diseases and medication usage were significantly associated with the risk of dementia in cohort of Parkinson’s disease after the adjustment for confounding variables (Table 2). The association decreased significantly between dementia and the usage of TCM (adjusted odds ratio = 0.67, P < 0.001) and statin (adjusted odds ratio = 0.57, P < 0.001). However, there was a markedly increasing association between dementia and CKD (adjusted odds ratio = 1.96, P = 0.001), COPD (adjusted odds ratio = 1.76, P < 0.001) and stroke (adjusted odds ratio = 1.90, P < 0.001) (Table 2).
Table 2
Conditional logistic regression of risk of dementia
| Crude OR | 95% C.I. | p-value | Adjusted OR† | 95% C.I. | p-value |
TCM | 0.68 | 0.56–0.82 | < 0.001 | 0.67 | 0.54–0.82 | < 0.001 |
Hypertension | 1.17 | 0.96–1.43 | 0.111 | 1.05 | 0.84–1.3 | 0.685 |
Hyperlipidemia | 0.72 | 0.58–0.89 | 0.002 | 0.90 | 0.69–1.18 | 0.454 |
Chronic liver disease | 1.07 | 0.81–1.41 | 0.623 | 1.18 | 0.87–1.59 | 0.289 |
Chronic kidney disease | 1.91 | 1.33–2.74 | < 0.001 | 1.96 | 1.33–2.91 | 0.001 |
Diabetes | 1.09 | 0.9–1.32 | 0.360 | 1.08 | 0.87–1.34 | 0.491 |
COPD | 1.86 | 1.47–2.35 | 0.000 | 1.76 | 1.37–2.26 | < 0.001 |
Autoimmune disease | 1.37 | 0.72–2.62 | 0.332 | 1.26 | 0.64–2.48 | 0.506 |
Cardiovascular disease | 1.01 | 0.83–1.23 | 0.918 | 1.02 | 0.81–1.27 | 0.884 |
Stroke | 1.85 | 1.54–2.23 | < 0.001 | 1.90 | 1.56–2.32 | < 0.001 |
Gout | 0.92 | 0.69–1.22 | 0.564 | 0.92 | 0.67–1.25 | 0.581 |
Warfarin | 1.28 | 0.76–2.16 | 0.355 | 1.20 | 0.68–2.1 | 0.529 |
Statin | 0.63 | 0.51–0.78 | < 0.001 | 0.57 | 0.43–0.75 | < 0.001 |
COPD: Chronic obstructive pulmonary disease. |
TCM: Traditional Chinese medicine. |
†Adjusted for TCM, hypertension, hyperlipidemia, chronic liver disease, chronic kidney disease, diabetes, COPD, autoimmune disease, cardiovascular disease, stroke, gout, warfarin, and statin. |
The risk of dementia in cohort of Parkinson’s disease was also associated with the duration of usage of Traditional Chinese Medicine (Table 3). The risk of dementia was significantly decreased with the usage of both TCM < 90 days (adjusted odds ratio, 0.69; 95% CI, 0.54–0.86) and ≥ 90 days (adjusted odds ratio, 0.62; 95% CI, 0.44–0.88), especially in the group who used TCM for more than 90 days.
Table 3
Conditional logistic regression of risk of dementia
| N | No. of dementia | Crude OR | 95% C.I. | p-value | Adjusted OR† | 95% C.I. | p-value |
TCM (days) | | | | | | | |
None | 1290 | 686 | 1 | | | 1 | | |
< 90 | 499 | 223 | 0.70 | 0.56–0.87 | 0.001 | 0.69 | 0.54–0.86 | 0.001 |
≥ 90 | 173 | 72 | 0.63 | 0.46–0.87 | 0.005 | 0.62 | 0.44–0.88 | 0.007 |
TCM: Traditional Chinese medicine. |
†Adjusted for TCM, hypertension, hyperlipidemia, chronic liver disease, chronic kidney disease, diabetes, COPD, autoimmune disease, cardiovascular disease, stroke, gout, warfarin, and statin. |
Though no statistically significant interaction was found among the risk of dementia in cohort of Parkinson’s disease and the TCM usage for < 90 days or ≥ 90 days between the age of 50 to 64 years, protection tendency was revealed (adjusted odds ratio, 0.30 and 0.07, respectively). Among the patients older than 65 years old, the risk of dementia was significantly decreased with the usage of TCM for < 90 days (adjusted odds ratio, 0.71; 95% CI, 0.56–0.9) and ≥ 90 days (adjusted odds ratio, 0.67; 95% CI, 0.47–0.95) (Table 4).
Table 4
Subgroup analysis of conditional logistic regression of risk of dementia
| N | No. of dementia | Crude OR | 95% C.I. | p-value | Adjusted OR | 95% C.I. | p-value |
Age = 50–64 | | | | | | | | |
TCM (days)† | | | | | | | | |
None | 47 | 28 | 1 | | | 1 | | |
< 90 | 26 | 11 | 0.45 | 0.13–1.53 | 0.199 | 0.30 | 0.06–1.56 | 0.152 |
≥ 90 | 11 | 3 | 0.11 | 0.01–0.97 | 0.047 | 0.07 | 0.005–1.03 | 0.052 |
Age ≥ 65 | | | | | | | | |
TCM (days)‡ | | | | | | | | |
None | 1243 | 658 | 1 | | | 1 | | |
< 90 | 473 | 212 | 0.72 | 0.58–0.90 | 0.004 | 0.71 | 0.56–0.90 | 0.004 |
≥ 90 | 162 | 69 | 0.68 | 0.49–0.94 | 0.020 | 0.67 | 0.47–0.95 | 0.025 |
Female | | | | | | | | |
TCM (days)‡ | | | | | | | | |
None | 683 | 368 | 1 | | | 1 | | |
< 90 | 269 | 117 | 0.63 | 0.46–0.85 | 0.003 | 0.64 | 0.46–0.9 | 0.010 |
≥ 90 | 82 | 32 | 0.52 | 0.32–0.86 | 0.010 | 0.50 | 0.29–0.86 | 0.013 |
Male | | | | | | | | |
TCM (days)‡ | | | | | | | | |
None | 607 | 318 | 1 | | | 1 | | |
< 90 | 230 | 106 | 0.78 | 0.57–1.06 | 0.110 | 0.71 | 0.51–0.99 | 0.042 |
≥ 90 | 91 | 40 | 0.73 | 0.48–1.12 | 0.156 | 0.70 | 0.44–1.10 | 0.124 |
TCM: Traditional Chinese medicine. |
†: Adjusted for TCM, hypertension, hyperlipidemia, chronic liver disease, diabetes, stroke, gout and statin. |
‡: Adjusted for TCM, hypertension, hyperlipidemia, chronic liver disease, chronic kidney disease, diabetes, COPD, autoimmune disease, cardiovascular disease, stroke, gout, warfarin, and statin. |
Among female patients, the risk of dementia was markedly decreased with the usage of TCM for < 90 days (adjusted odds ratio, 0.64; 95% CI, 0.46–0.9) and ≥ 90 days (adjusted odds ratio, 0.50; 95% CI, 0.29–0.86). Among male patients, TCM usage for less than 90 days was beneficial for reducing the risk of dementia (adjusted odds ratio, 0.71; 95% CI, 0.51–0.99), but TCM usage for more than 90 days demonstrated no statistical significance; nonetheless, the protection tendency in this group was also revealed (adjusted odds ratio, 0.70). (Table 4)