In this study, we explored the association between serum lipid profiles and cognitive impairment in China Hainan centenarians. We found that high HDL-C were associated with an decreased prevalence of cognitive impairment, and this association remained significant after adjusting for demographic and other potential confounders. Serum concentrations of TC, TG, and LDL-C showed no association with cognitive impairment. Our results expanded the knowledge that high levels of HDL-C are associated with better cognitive function in centenarian.
Table 2 Significant associates for cognitive impairments by multiple logistic regression
|
OR
|
95% CI
|
P
|
TC
|
1.612
|
0.798
|
3.255
|
0.183
|
TG
|
0.941
|
0.685
|
1.294
|
0.709
|
HDL-C
|
0.350
|
0.159
|
0.774
|
0.009
|
LDL-C
|
0.598
|
0.273
|
1.308
|
0.198
|
Age
|
0.986
|
0.929
|
1.045
|
0.631
|
Female
|
0.887
|
0.551
|
1.428
|
0.621
|
Illiterate
|
0.742
|
0.395
|
1.393
|
0.354
|
Han ethnic
|
1.429
|
0.819
|
2.493
|
0.209
|
Current smoker
|
0.803
|
0.325
|
1.987
|
0.635
|
Current alcohol drinker
|
1.025
|
0.588
|
1.788
|
0.929
|
Current tea drinker
|
0.807
|
0.286
|
2.280
|
0.686
|
ADL impairments
|
2.283
|
1.533
|
3.400
|
0.000
|
Outdoor activities >1 h/d
|
0.485
|
0.346
|
0.681
|
0.000
|
Living with families
|
0.940
|
0.584
|
1.511
|
0.797
|
Relatives contacts
|
0.543
|
0.305
|
0.966
|
0.038
|
Frequent meat intake
|
1.183
|
0.733
|
1.907
|
0.491
|
Frequent poultry intake
|
1.101
|
0.760
|
1.596
|
0.611
|
Frequent fish intake
|
0.553
|
0.393
|
0.779
|
0.001
|
Frequent milk drinking
|
0.963
|
0.642
|
1.443
|
0.854
|
Frequent eggs intake
|
0.617
|
0.421
|
0.905
|
0.013
|
Frequent fruit intake
|
0.832
|
0.579
|
1.196
|
0.321
|
Frequent vegetable intake
|
0.474
|
0.212
|
1.058
|
0.068
|
SBP
|
0.991
|
0.983
|
1.000
|
0.049
|
DBP
|
1.007
|
0.990
|
1.024
|
0.417
|
BMI
|
0.966
|
0.913
|
1.022
|
0.228
|
Elevated serum HDL-C levels have been shown to be protective against adverse health outcomes in elderly subjects, including cardiovascular disease, stroke and cognitive impairment [10, 11, 21, 22]. Among people aged 80 years or older, higher
Table 3 ORs for Cognitive Impairment over Strata of Lipid Concentrations
|
Q1
|
Q2
|
Q3
|
Q4
|
P for trend
|
TC
|
|
|
|
|
|
Mean (range)
|
3.47 (1.34-4.02)
|
4.33 (4.03-4.58)
|
4.90 (4.59-5.26)
|
6.01 (5.27-8.85)
|
|
Model 1
|
1.00 (Reference)
|
1.03 (0.64, 1.67)
|
1.63 (0.88, 3.02)
|
1.20 (0.53, 2.72)
|
0.285
|
Model 2
|
1.000(Reference)
|
0.86 (0.48, 1.56)
|
1.49 (0.71, 3.15)
|
1.22 (0.46, 3.22)
|
0.348
|
TG
|
|
|
|
|
|
Mean (range)
|
0.66 (0.34-0.80)
|
0.91 (0.81-1.03)
|
1.20 (1.04-1.40)
|
1.18 (1.41-9.99)
|
|
Model 1
|
1.00 (Reference)
|
0.73 (0.49, 1.07)
|
0.82 (0.55, 1.21)
|
0.74 (0.48, 1.14)
|
0.332
|
Model 2
|
1.00 (Reference)
|
0.64 (0.40, 1.02)
|
0.90 (0.56, 1.45)
|
0.87 (0.52, 1.47)
|
0.959
|
HDL
|
|
|
|
|
|
Mean (range)
|
0.98 (0.50-1.17)
|
1.28 (1.18-1.39)
|
1.52 (1.40-1.67)
|
1.97 (1.68-2.87)
|
|
Model 1,
|
1.00 (Reference)
|
0.67 (0.46, 0.98)
|
0.50 (0.33, 0.76)
|
0.49 (0.30, 0.78)
|
0.001
|
Model 2
|
1.00 (Reference)
|
0.69 (0.44, 1.10)
|
0.553 (0.34, 0.91)
|
0.51 (0.29, 0.92)
|
0.012
|
LDL
|
|
|
|
|
|
Mean (range)
|
1.88 (0.64-2.28)
|
2.48 (2.29-2.72)
|
2.97 (2.73-3.25)
|
3.87 (3.26-6.76)
|
|
Model 1
|
1.00 (Reference)
|
0.99 (0.63, 1.56)
|
0.51 (0.28, 0.91)
|
0.66 (0.31, 1.40)
|
0.057
|
Model 2
|
1.00 (Reference)
|
1.25 (0.72, 2.17)
|
0.72 (0.36, 1.46)
|
0.80 (0.32, 1.97)
|
0.274
|
Mean (range): mmol/L; Model 1 and Model 2: OR (95% CI).
Model 1: No adjusted. Model 2: Adjusted for the potential covariates listed in Table 2.
HDL-C concentration was independently associated with better functional status, physical performance and survival [23, 24]. Serum HDL-C was found to be a protective predictor of executive function in older patients with diabetes mellitus[25]. Lower HDL-C concentration was associated with cognitive impairment and clinical diagnosis of dementia in the oldest old [10]. In our study, high HDL-C levels were found to be associated with lower adjusted odds (OR=0.51) of cognitive impairment. This result is in accordance with previous studies.
Several studies reported that TC and LDL-C are related to cognitive impairment in China old adults [12, 13]. In our study, no associations were found between TC, TG and LDL-C and cognitive impairment in China centenarians. Further studies are required to explore the possible roles of TC and LDL-C in maintaining cognitive function in the oldest-old.
There are some hypotheses that may explain the observed association between HDL-C and cognitive impairment. First, HDL-C prevents atherosclerosis progression and cause regression of established atherosclerotic lesions through its reverse cholesterol transport capacity [26]. Increasing HDL-C concentration reduces the risk for atherosclerotic disease and stroke which are important risk factors for cognitive impairment [27]. Second, HDL-C has effects of antioxidant, anti-inflammatory, inhibition of platelet aggregation, and improvement of endothelial function [26]. Those effects are also critical in atheroprotective progression. Third, HDL cholesterol is the predominant lipoprotein in the human brain, where it can prevent aggregation of amyloid-β peptide and the development of neurodegeneration [7, 28]. This might slow or even prevent the development of cognitive impairment.
Age is a significant risk determinant of cognitive impairment [3, 29] and the incidence of severe cognitive impairment continues to rise exponentially after the age of 90 [30]. In this study, the incidence of cognitive impairment in China centenarians was 38.7% (95% CI, 35.6–41.9%). Given that HDL-C is a protective factor for cognitive impairment, normalization of HDL-C levels may become a future strategy to prevent the development of cognitive impairment in long-lived persons. The change of blood HDL-C concentration may be as an effective indicator for cognitive functions change in elderly persons. These hypotheses should be further tested in appropriately designed, randomized, controlled trials.
While highlighting the strengths of our study, several limitations must be mentioned. First, this study was cross-sectional designed, and thus causality could not be inferred. Further longitudinal studies are needed to confirm the association between HDL-C and cognitive impairment in the Chinese oldest-old. Second, the diagnosis of cognitive impairment were not confirmed by clinical neurologists and errors were exist possibly in the detection by general practitioners. Therefore, the effects of HDL-C, TC, TG and LDL-C on cognitive impairment might be overestimated or underestimated in this study. Although MMSE is a widely used test in evaluation of cognitive function, it is problematic when specifically used in examining cognitive performance in oldest old participants [31, 32]. MMSE scores of centenarians were easily influenced by health problems, illiteracy (the majority of Hainan centenarians received no education), sensory impairment and physical disability, and might not reflect the actual level of cognitive function in centenarians. Objective and practical methods should be developed to evaluate the cognitive functions of centenarians. Third, our subjects are unlikely to be completely representative of the entire China centenarians, because they were all recruited from Hainan Province which is an independent sea island area and has a low proportion of immigrants.