This study revealed that the risk of dementia in the CKD cohort was higher than that in the non-CKD cohort yield a HR of 1.04 after controlling for demographic variables and medical conditions. This result is comparable with the findings in previous studies. Nickolas et al. found that the mild cognitive impairment in older adults with CKD is also a potentially modifiable risk factor for dementia . Another survey revealed that moderate to severe CKD in stroke-free subjects was associated with white matter hyperintensity, which is resulted from inflammation and endothelial dysfunction and is a risk for dementia [22, 23]. In addition, the present study supports previous findings of the relationship between impaired kidney function and cognitive decline [16, 17, 22, 24–26]. Kahtri et al found that patients with kidney disease even with mild CKD 訂 e at an elevated risk of cognitive impairment .
It is important to note that a large proportion of CKD patients were young, aged 20-39 years, accounting for approximately 15% in the cohort. The young CKD patients to the young non- CKD patients IRR of dementia was near 9-fold greater than that for the elderly, reflecting CKD has a strong impact for young people. The corresponding IRR for 40-64 years was 13.6-fold greater than the elderly. Our data also showed that the risk of dementia declined with longer follow-up time, indicating dementia may develop in earlier period of CKD. Prevention care should be started earlier period including younger CKD patients.
This study also found several comorbidities and medications could predict dementia. The associations between blood pressure, diabetes and dementia and cognitive impairment have received much attention in studies, but the results are somewhat in conflict [25–32]. High blood pressure increases the risk of dementia in the elderly [26, 30]. Xu et al. found that the risk of dementia was especially high for patients with diabetes mellitus and severe systolic hypertension . Our results echo most of previous findings that hypertension and diabetes are independent predictors of dementia .
An earlier study has found that very old women with myocardial infarction are 5-time more likely prone to dementia than those without the disease . The cross-sectional analysis from the Rotterdam study showed that the prevalence of dementia was increased with the degree of peripheral arterial atherosclerotic disease. The odds ratio for cognitive decline in those with severe atherosclerosis was 3:0 . Our study showed that CKD patients with ischemic heart disease were 2.8-fold (17.0 vs. 6.05 per 1000 person-years) more likely than CKD patients without the comorbidity for the risk of dementia. This association became insignificant in the multivariate analysis.
Among comorbidities, alcoholism has the strongest association with dementia in this study. Breteler found a significant relationship between alcohol intake and the risk of vascular disease . Those with moderate alcohol intake may not at an increased risk of dementia [36–38]. The congnitive impairment due to alcohol addition has been 臼 ported as alcohol dementia [29, 39]. Alcoholism was less prevalent in our study population,but it is an important risk factor of dementia.
In addition to alcoholism, hypertension and diabetes, we also found that cerebrovascular disease, Parkinson's disease and major depressive disorder were significant comorbidities associated with dementia. Studies have reported cerebrovascular disease as a major contributor to later-life dementia [31, 40–44]. Our findings reiterate previous pathological investigations. The later epidemiological studies may have raised the possibility that cerebrovascular disease and dementia are two disorders causally related . Parkinson's disease and the major depressive disorder are relatively less important than cerebrovascular disease in the association with the dementia risk [45–47].
Hyperlipidemia had a significant risk of dementia in the univariate model but it became a protective effect after being adjusted. In subjects without hyperlipidemia, the incidence of dementia in CKD patients is higher than non-CKD patients (9.36 vs. 5.33 per 1,000 person-years). However ,the incidence in CKD patients with hyperlipidemia declined to 9.14 per 1,000 person-years. The association between hyperlipidemia and dementia is not clear. The colinearity of hypertension and hyperlipidemia may explain the phenomenon.
The significant relation between dementia and medications of benzodiazepines agents and aspirin is another important finding in this study. Previous studies have reported that the long-term use of benzodiazepines agents is responsible for moderate-to-large weighted risk of dementia [48–52]. The aspirin use might pose an increased risk of intracerebral hemorrhages . It is not clear whether this is the mechanism increases the risk of dementia.
The insurance claims data provided no measures of serum creatinine and microalbuminuria, and we were unable to evaluate the dementia risk based on kidney function. CKD patients at an earlier stage might not be included in the study. This may, therefore, have resulted in estimating the risk for patients with more severe condition of CKD. Second, as diagnosis of CKD and dementia requires long-term observation for clinical manifestation, the seven-year or less observation period in this study may be insufficient to estimate the dementia risk with the full course of natural history. The associated risk measures may be thus underestimated.
Third, this study included conmorbidity information at the baseline, prior to the date of establishing the study cohorts. Comorbidities developed during the follow-up period may vary and the estimation of dementia risk may vary.