Plasma Cholesterol Levels as Potential Nutritional Biomarkers for Lewy Body Dementia

Abstract

Background:

The relationship between cholesterol level and the risk of developing Alzheimer’s disease has been well established, but the relationship between cholesterol level and Lewy body dementia (LBD) is still not well known.

Objective:

The aim of this case-control study was to explore the association between blood cholesterol levels and LBD in Chinese older adults.

Methods:

A total of 65 patients with LBD and 110 older adult controls were enrolled during the study period. The levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting glucose were measured separately. The associations between LBD, blood cholesterol levels, and fasting glucose levels were assessed using multiple binary logistic regression analyses adjusted for multiple covariates.

Results:

Increased plasma LDL-C levels and lower HDL-C levels were independently associated with the risk of LBD in models adjusted for age, sex, education, alcohol use status, smoking status, and vascular disorders. Higher fasting glucose levels may be associated with the risk of LBD.

Conclusion:

The results of this study suggest that elevated levels of LDL-C and reduced levels of HDL-C were associated with LBD development and therefore are potential nutritional risk factors for LBD. Adjusting diet and individualized and effective cholesterol-lowering therapy in high-risk adults may aid in the prevention or management of LBD.

Keywords

Cholesterol fasting glucose high-density lipoprotein cholesterol Lewy body dementia low-density lipoprotein cholesterol

INTRODUCTION

Lewy body dementia (LBD) is the second most frequent cause of neurodegenerative dementia after Alzheimer’s disease (AD) affecting older adults [1]. There are both differences and similarities in the clinical and pathological features between LBD and other neurodegenerative diseases such as AD and Parkinson’s disease (PD) [2, 3]. All these diseases are characterized by the accumulation of α-synuclein protein, a major component of Lewy bodies [2, 4]. Cholesterol is vital to neuronal structure and function, and high cholesterol levels have been reported to be a prognostic risk factor for neurodegenerative dementia, particularly AD [5]. Normally, the blood-brain barrier effectively prevents the exchange of brain tissue and plasma lipoproteins. High cholesterol levels in plasma increases the permeability of blood-brain barrier, allowing the peripheral cholesterol to enter the central nervous system, resulting in abnormal cholesterol metabolism in the brain [6]. Cholesterol plays potentially important roles in the synthesis, deposition, and clearance of amyloid-β (Aβ) [7], which is the main pathological basis for AD. Apolipoprotein E (APOE) ɛ4 is a well-established genetic risk factor for AD; it has been reported that individuals who are homozygous for APOE ɛ4 and who have hypercholesterolemia are at a 13-fold increased risk of developing AD [8]. The role of APOE in LBD has also been established, and APOE ɛ4 may also represent a genetic risk factor for LBD [9].

There is convincing evidence that α-synuclein is a major component of the aggregates that form the amyloid fibrils in LBD [10]; therefore, the factors that change the regulatory mechanism of α-synuclein may be also related to the pathogenesis of LBD. It has been demonstrated that oxidative cholesterol metabolites accelerate α-synuclein aggregation and hasten the formation of α-synuclein fibrils in LBD [10]. The α-synuclein protein has been implicated in the regulation of neuronal cholesterol. Cholesterol facilitates interactions between α-synuclein oligomers, and abnormal cholesterol can lead to the loss of dopaminergic neurons in individuals with PD who are positive for GBA1, the gene coding for GCase [11]. Nevertheless, the strict relationship between serum cholesterol levels and LBD has been, to our knowledge, evaluated by few studies. Nevertheless, to our knowledge, the strict relationship between serum cholesterol levels and LBD remains unclear. In order to better understand the relationship between serum cholesterol levels and LBD, we conducted this case-control study.

METHODS

Patients and controls

From September 2018 and April 2021, a total of 65 patients in the LBD group and 110 older adult controls were recruited from the cognitive impairment clinic of Tianjin Huanhu Hospital. The study was conducted in accordance with local clinical research regulations and informed consent was required.

Cases were diagnosed as probable LBD by experienced neurologists on the basis of published criteria [12]. The controls were included if they lacked serious physical diseases, were able to complete the neuropsychological tests, and had no known neurologic disorders or cognitive impairment. None of the subjects used statin medications or other lipid-modifying agents.

Adopted exclusionary criteria were 1) a history of psychiatric disorder; 2) cerebrovascular disorders, hydrocephalus, and intracranial mass, documented by computed tomography or magnetic resonance imaging within the past 12 months; 3) abnormalities in serum folate and vitamin B12, syphilis serology, or thyroid hormone levels; 4) a history of traumatic brain injury or another neurologic disease; and 5) significant unstable systemic illness or organ failure.

Clinical assessment

The medical history was collected from the patients’ medical records and a formal questionnaire. Data included the number of years of education, Mini-Mental State Examination (MMSE) score, current smoking status (yes/no), alcohol status (yes/no), heart disease, hypertension, stroke, and type 2 diabetes mellitus (T2DM). Heart disease was defined as a history of angina pectoris, coronary artery disease, atrial fibrillation, myocardial infarction, and congestive heart failure.

Serum cholesterol and fasting glucose levels measurement

All participants started fasting at 8 pm. On the morning following enrolment into the study, blood samples were drawn through vein puncture after at least a 12-h fasting period. Blood from each patient was collected into a 5 mL tube (BD, Plymouth, United Kingdom) containing inert separation glue and coagulant. The tube was centrifuged at 3000 g for 10 min, after which serum samples were obtained [5].

Serum samples were collected for measuring fasting glucose, total cholesterol (TC), low-den-sity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Fasting glucose levels were detected by hexokinase (Beckman Coulter, USA). The concentrations of TG, TC, and HDL were measured using an automatic chemical analyzer (Beckman AU5800, USA) [13]. The LDL levels were estimated using the Friedewald formula: LDL = TC –HDL –(TG/5) [14]. The concentrations of serum lipids, lipoproteins, and fasting glucose were grouped into four equal strata each representing decreasing concentrations.

Ethical consideration

This research, which involves human subjects, has complied with all the relevant national regulations and institutional policies and is in accordance with the tenets of the Declaration of Helsinki. Further, this study has been approved by the Medical Ethics Committee of Tianjin Huanhu Hospital.

Statistical analysis

All statistical tests were performed using SPSS, version 19.0 for Windows (SPSS Inc, Chicago, IL, USA). p values < 0.05 were considered statistically significant. The data were presented as mean±SD, median (interquartile range [IQR]), or absolute numbers and proportions. The quantitative variables were assessed for normality using histograms and quartile-quartile plots. Differences in the study characteristics between the cases and controls were assessed using Student t tests for quantitative variables that showed a normal distribution or that were normally distributed after logarithmic transformation. Differences between categorical variables were assessed using χ² tests. Logistic regression models were used to evaluate odds ratios (ORs) and 95% CIs for the associations between LBD and serum lipid levels. After adjusting for sex, age, and education, a second model was created, further adjusting for current smoking status, alcohol use status, stroke, T2DM, hypertension, heart disease, spouse/partner, and family medical history.

RESULTS

A total of 175 participants were enrolled during the study period. Among them, a total of 65 patients in the LBD group (mean±SD age, 71.48±8.04 years; 35 women [53.85%]) and 110 older adult controls (mean±SD age, 70.47±5.83 years; 59 women [53.64%]) were recruited. Table 1 summarizes the demographic and clinical characteristics of all patients. There were significant differences in the family medical history, current smoking status, and alcohol use status between the patients with LBD and the controls. The LBD group had lower MMSE scores but higher fasting glucose and LDL-C levels than the controls (Table 1). There were no significant differences in sex, age, or education level among the LBD groups and control groups. Further comparisons of the clinical characteristics showed that a history of stroke was higher in the LBD group than in the control group (p = 0.01) (Table 1). The following are the interquartile ranges measured for each of the blood lipid levels: TC (1.00–9.24 mmol/L), TG (0.44–7.20 mmol/L), HDL-C (0.88–3.32 mmol/L), LDL-C (0.92–6.71 mmol/L), and fasting glucose (3.99–11.82 mmol/L) (Table 2).

Table 1

Clinical and demographic characteristics in elderly patients

Characteristics	Control group (n = 110)	LBD group (n = 65)	p
Age, y (mean±SD)	70.47±5.83	71.48±8.04	0.381
Female sex, n (%)	59 (53.64)	35 (53.85)	0.979
Education, y (mean±SD)	9.07±3.01	9.85±4.96	0.258
MMSE score (mean±SD)	25.59±1.21	15.77±6.41	0.000
Spouse, n (%)	12 (10.91)	13 (20.00)	0.097
Family medical history, n (%)	3 (2.73)	19 (29.23)	0.000
Current smoking, n (%)	12 (10.91)	15 (23.08)	0.031
Alcohol, n (%)	5 (4.55)	12 (18.46,)	0.003
Lipid, mmol/L
TC (mean±SD)	5.02±0.96	5.18±1.29	0.381
TG (median [IQR])	1.30 (1.00–1.80)	1.16 (0.82–2.06)	0.370
HDL-C (median [IQR])	1.63 (1.35, 1.71)	1.34 (1.13, 1.62)	0.351
LDL-C (mean±SD)	2.62±0.79	3.23±1.00	0.000
Fast glucose, mmol/L, (median [IQR])	5.40 (5.10, 5.89)	5.86 (5.49, 6.31)	0.028
Vascular disorders, n (%)
Stroke	3 (2.73)	9 (13.85)	0.010
T2DM	14 (12.73)	12 (18.46)	0.303
Hypertension	37 (33.64)	26 (40.00)	0.397
Heart disease	5 (4.55)	6 (9.23)	0.217

HDL-C, high-density lipoprotein cholesterol; IQR, interquartile range; LBD, Lewy body dementia; LDL-C, low-density lipoprotein cholesterol; MMSE, Mini-Mental State Exam; TC, total cholesterol; TG, triglycerides; T2DM, type 2 diabetes mellitus.

Table 2

Biochemical status categories based on blood lipid levels^a

Lipid, Quartile (Range, mmol/l)	n	TC 1.00–9.24 mmol/l	TG 0.44–7.20 mmol/l	HDL-C 0.88–3.32 mmol/l	LDL-C 0.92–6.71 mmol/l	Fast glucose 3.99–11.82 mmol/l
TC
1 (≤4.39)	39	3.72±0.62	1.10 (0.90–1.40)	1.58 (1.26–1.71)	2.06±0.44	5.60 (5.10–6.12)
2 (4.40–5.09)	40	4.72±0.21	1.28 (1.00–1.60)	1.64 (1.29–1.74)	2.40±0.60	5.62 (5.11–5.98)
3 (5.10–5.89)	38	5.42±0.25	1.40 (0.98–2.22)	1.40 (1.18–1.64)	3.02±0.66	5.52 (5.10–6.15)
4 (≥5.90)	42	6.36±0.60	1.40 (0.97–2.09)	1.62 (1.35–1.69)	3.76±0.83	5.44 (5.11–5.96)
TG
1 (≤0.90)	40	4.86±1.03	0.78 (0.63–0.90)	1.67 (1.56–1.72)	2.61±0.81	5.51 (5.16–5.86)
2 (0.91–1.29)	38	4.96±0.96	1.08 (1.00–1.17)	1.58 (1.30–1.71)	2.72±0.86	5.48 (5.10–6.10)
3 (1.30–1.82)	41	5.11±1.19	1.50 (1.35–1.59)	1.66 (1.46–1.71)	2.67±0.91	5.50 (5.20–6.10)
4 (≥1.83)	40	5.32±1.10	2.51 (2.10–3.00)	1.19 (1.07–1.35)	3.23±0.94	5.70 (5.10–6.10)
HDL-C
1 (≤1.23)	41	5.05±0.94	2.30 (1.53–2.82)	1.11 (1.02–1.16)	3.05±0.88	5.79 (5.20–6.20)
2 (1.24–1.57)	43	5.13±1.01	1.20 (0.95–1.88)	1.35 (1.28–1.48)	3.07±0.82	5.62 (5.15–6.18)
3 (1.58–1.69)	43	5.16±1.19	1.20 (0.90–1.42)	1.63 (1.62–1.67)	2.82±0.70	5.54 (5.16–6.12)
4 (≥1.70)	42	4.99±1.14	1.00 (0.90–1.40)	1.76 (1.71–1.84)	2.52±1.15	5.30 (5.08–5.80)
LDL-C
1 (≤2.13)	42	4.29±0.64	1.01 (0.90–1.50)	1.71 (1.32–1.76)	1.78±0.24	5.40 (5.05–5.85)
2 (2.14–2.80)	43	4.59±0.85	1.20 (0.90–1.50)	1.64 (1.33–1.71)	2.41±0.21	5.44 (5.10–5.82)
3 (2.81–3.43)	43	5.35±0.96	1.28 (1.00–2.00)	1.40 (1.19–1.63)	3.16±0.16	5.70 (5.20–6.20)
4 (≥3.44)	42	6.19±0.74	1.53 (0.94–2.40)	1.37 (1.14–1.64)	4.09±0.59	5.60 (5.20–6.30)
Fast glucose
1 (≤5.10)	40	5.06±1.02	1.29 (0.99–1.88)	1.63 (1.31–1.72)	2.62±0.83	4.86 (4.60–5.10)
2 (5.11–5.57)	39	5.17±1.06	1.08 (0.90–1.40)	1.64 (1.38–1.70)	2.75±0.89	5.30 (5.22–5.49)
3 (5.58–6.09)	39	5.01±0.90	1.35 (0.90–2.00)	1.50 (1.23–1.69)	2.75±0.80	5.80 (5.70–5.90)
4 (≥6.10)	40	4.96±1.31	1.46 (1.02–2.23)	1.55 (1.19–1.66)	1.06±0.17	6.88 (6.20–8.28)

HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride. ^aValues are presented as No., mean±SD, or median (interquartile range).

A multivariate logistic regression analysis was conducted to assess the association between the quartiles of serum lipid and fasting glucose levels and the risk of LBD. A higher serum LDL-C level was found to be positively associated with the risk of LBD in the model adjusted for age, sex, and education (basic model) (Table 3). This association was strengthened after further adjusting for current smoking status, alcohol use status, spouse, family medical history, history of stroke, hypertension, T2DM, and heart disease (final model) (Table 3).

Table 3

Multivariate logistic regression analysis of the associations between the quartiles of serum lipid levels and risk of Lewy body dementia

Lipid, Quartile (Range, mg/dL)	No. (%) of subjects		Basic model^a		Final model^b
	Control group (n = 110)	LBD group (n = 65)	OR (95% CI)	p	OR (95% CI)	p
TC
1 (≤4.39)	26 (24.30)	13 (25.00)	1 (reference)		1 (reference)
2 (4.40–5.09)	30 (28.04)	10 (19.23)	0.786 (0.282–2.190)	0.645	0.913 (0.275–3.032)	0.882
3 (5.10–5.89)	25 (23.36)	13 (25.00)	1.129 (0.431–2.957)	0.806	1.021 (0.316–3.299)	0.972
4 (≥5.90)	26 (24.30)	16 (30.77)	1.405 (0.541–3.647)	0.485	1.208 (0.360–4.051)	0.759
Trend test				0.704		0.975
TG
1 (≤0.90)	24 (22.43)	16 (30.78)	1 (reference)		1 (reference)
2 (0.91–1.29)	24 (22.43)	14 (26.92)	0.874 (0.349–2.189)	0.773	1.335 (0.396–4.495)	0.641
3 (1.30–1.82)	33 (30.84)	8 (15.38)	0.362 (0.131–0.999)	0.050	0.689 (0.200–2.371)	0.555
4 (≥1.83)	26 (24.30)	14 (26.92)	0.816 (0.325–2.046)	0.664	1.399 (0.421–4.647)	0.584
Trend test				0.228		0.624
HDL-C
1 (≤1.23)	17 (15.89)	24 (38.71)	1 (reference)		1 (reference)
2 (1.24–1.57)	24 (22.43)	19 (30.65)	0.554(0.231–1.327)	0.185	0.653 (0.232–1.834)	0.418
3 (1.58–1.69)	31 (28.97)	12 (19.35)	0.263 (0.105–0.659)	0.004	0.205 (0.064–0.656)	0.008
4 (≥1.70)	35 (32.71)	7 (11.29)	0.141 (0.051–0.395)	0.000	0.173 (0.052–0.577)	0.004
Trend test				0.001		0.006
LDL-C
1 (≤2.13)	34 (31.78)	8 (12.70)	1 (reference)		1 (reference)
2 (2.14–2.80)	32 (29.90)	11 (17.46)	1.476 (0.525–4.147)	0.460	1.152 (0.317–4.180)	0.830
3 (2.81–3.43)	23 (21.50)	20 (31.75)	3.730 (1.403–9.915)	0.008	3.039 (0.897–10.299)	0.074
4 (≥3.44)	18 (16.82)	24 (38.09)	5.556 (2.059–14.992)	0.001	6.919 (2.055–23.297)	0.002
Trend test				0.001		0.004
Fast glucose
1 (≤5.10)	35 (32.41)	5 (10.00)	1 (reference)		1 (reference)
2 (5.11–5.57)	27 (25.00)	12 (24.00)	3.075 (0.964–9.815)	0.058	2.239 (0.593–8.450)	0.234
3 (5.58–6.09)	25 (23.15)	14 (28.00)	3.949 (1.258–12.396)	0.019	2.495 (0.657–9.482)	0.179
4 (≥6.10)	21 (19.44)	19 (38.00)	6.273 (2.033–19.354)	0.001	5.348 (1.443–19.826)	0.012
Trend test				0.015		0.090

HDL-C, high-density lipoprotein cholesterol; LBD, Lewy body dementia; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; TC, total cholesterol; TG, triglyceride. ^aAdjusted for age, sex, and education level. ^bAdjusted for age, sex, education level, spouse, family medical history, current smoking, alcohol, stroke, hypertension, type 2 diabetes mellitus, and heart disease.

We also found that lower serum HDL-C levels were significantly associated with the risk of LBD in the basic model and the final model. On the other hand, TC and TG were not significant predictors of LBD, and adjusting for demographics and vascular disorders did not change this relationship (Table 3).

Moreover, we also observed a positive correlation between higher fasting glucose levels and risk of LBD in the basic model (Table 3). In the final model, an association was also found for the fourth quartiles (odds ratio, 5.348; 95% CI, 1.443–19.826; p = 0.01); however, this trend did not reach statistical significance with respect to the control group (Trend test: p = 0.09) (Table 3).

DISCUSSION

Currently, there is no effective management of LBD, one of the most common forms of neurodegenerative dementia affecting older adults. Therefore, it is imperative to evaluate the risk factors of LBD. The family of LBD diseases is characterized by the accumulation of aggregated α-synuclein into Lewy bodies, which include PD, PD with dementia, and LBD [15]. Thus, the factors that change the regulatory mechanism of α-synuclein may be related to the pathogenesis of LBD. Results from a previous cohort study suggest that cholesterol exposure at age 70 years was predictive of LBD, and cholesterol exposures decades earlier in life may be important for the development of LBD [16]. Studies have demonstrated that hypercholesterolemia is involved in nigral dopaminergic neurodegeneration, and a high-fat diet exacerbates parkinsonian pathologies [17, 18]. The protein α-synuclein has been implicated in the regulation of neuronal cholesterol, and cholesterol facilitates interactions between α-synuclein oligomers. High blood cholesterol levels can lead to the loss of dopaminergic neurons in GBA1 PD [11]. In recent years, study results have reported serum cholesterol level to be a risk factor for multiple diseases involving neurodegenerative dementia, such as AD and frontotemporal dementia [19]. AD and LBD share many risk factors. A retrospective cohort study found that participants who had one or more metabolic risk factors (hypertension, T2DM, and hyperlipidemia) had significantly higher odds of developing AD or LBD, but no significant difference in metabolic risk factors was observed between patients with LBD and AD [20]. Nevertheless, the strict relationship between serum cholesterol levels and LBD remains unclear. In order to better understand the relationship between serum cholesterol levels and LBD, we conducted this case-control study.

Cholesterol and fasting glucose are risk factors that can be modified through a change in diet, lifestyle habits, and medications, thereby allowing for early intervention that can be used to prevent and delay LBD progression. We explored the associations between serum cholesterol and fasting glucose levels and the risk of LBD among 175 participants by adjusting for potentially confounding factors.

In this study, the serum LDL-C and fasting glucose levels were significantly different between the LBD group and control group. However, there was no significant different in TC or TG between the control group and LBD group. Initially, we observed that higher plasma LDL-C concentrations were associated with higher risk of LBD after adjusting for age, sex, and education level; these associations were strengthened after further adjusting for smoking, alcohol use status, history of stroke, hypertension, T2DM, and heart disease. Consistent with our study, several other studies found that cholesterol is vital to neuronal structure and function, and its disturbance has been shown to play a potentially important role in dementia. In a longitudinal study of Chinese older adults, higher blood TC and LDL-C levels were associated with higher risks of cognitive decline after adjusting for sociodemographic information, behavior and lifestyle, depression symptoms, physical examination, hypertension, and laboratory indices [21]. Other researchers have also suggested that higher TC and LDL-C concentrations are associated with faster cognitive decline and progression of AD [22, 23]. Another study also found that TC and LDL were positively correlated with the density of neuritic plaques in one of the AD markers [24]. A study on the relationship between plasma-oxidized LDL (OxLDL) levels, AD, and vascular dementia found that increased OxLDL levels were significantly associated with an increased risk of AD in men with a history of cardiovascular disease [25]. A possible biological mechanism may be that LDL-C is susceptible to oxidation, and the polymorphism of the OxLDL receptor limits the clearance of Aβ [26]. Normally, the blood-brain barrier effectively prevents the exposure of brain tissue to plasma lipoproteins. However, high cholesterol levels in the plasma increase the permeability of the blood-brain barrier, allowing for the peripheral cholesterol to enter the central nervous system [6]. In our study, higher levels of serum LDL-C were found to be positively associated with the risk of LBD development after adjusting for demographics and vascular disorders. However, we also found that TC and TG levels were not significantly associated with the risk of LBD development.

After adjusting for age, sex, and education, we found that lower HDL-C concentrations were associated with the higher risk of LBD; these associations were strengthened after further adjusting for current smoking status, history of stroke, hypertension, T2DM, and heart disease.

Consistent with the findings from our study, lower HDL-C levels have been previously reported to be associated with more severe white matter lesion changes, leading to AD and mild cognitive impairment; this represents a transitional stage between normal aging and AD [27]. The APOE ɛ4 allele is the strongest known genetic risk factor for sporadic AD and is also a risk factor for LBD [28]. Results from a meta-analysis revealed that APOE ɛ4 may influence the association between white matter hyperintensity volume and cognitive performance in AD and LBD [9]. In a longitudinal study, ApoE was confirmed to be a lipid carrier in both the peripheral and central nervous system, and HDL-C was found to be facilitated by APOE4 and to possibly have a protective effect on cognitive decline later in life [29, 30]. It has been reported that HDL-C might prevent aggregation and polymerization of Aβ in the human brain and that the anti-inflammatory properties of HDL-C could also prevent inflammation caused by neurodegenerative processes [31, 32]. In this study, we found that lower HDL-C levels were associated with a higher risk of LBD after adjusting for demographics and vascular disorders, which suggests that a higher plasma HDL-C level may be a protective factor against LBD development.

We also observed that a higher fasting glucose level was associated with LBD risk after adjusting for age, sex, and education (Trend test: p = 0.02). However, this association was weakened after further adjusting for current smoking status, alcohol use status, family history, stroke, hypertension, T2DM, and heart disease. In the final model, an association was also found for the fourth quartiles (odds ratio, 5.348; 95% CI, 1.443–19.826; p = 0.01); however, this trend did not reach statistical significance with respect to the control group (Trend test: p = 0.09) (Table 3). This may have been due to the small sample size.

Impaired glucose tolerance and diabetes are potential risk factors for the development of AD, but evidence for this assertion is conflicting. Some studies have shown that older patients with diabetes have higher rates of cognitive impairment [33]. Multiple linear regression analyses have revealed that persistent reduced glucose tolerance is associated with impaired cognitive function and hippocampal atrophy in the older adult population. However, other arguments take exactly the opposite point of view. A prospective longitudinal cohort study reported that there were no significant correlations between impaired glucose tolerance, diabetes, or insulin resistance and AD pathology or brain Aβ accumulation [34].

To our knowledge, few studies have addressed the relationship between fasting glucose level and LBD. Similarly, we did not find an association between diabetes and LBD. Yet, we observed that a higher fasting glucose level was associated with the risk of LBD after adjusting for age, sex, and education. However, this association was weakened after further adjusting for multiple factors. The relatively small sample size may have resulted in weakened associations. Additionally, we did not further evaluate the correlation between glucose tolerance and insulin resistance and LBD, which is a limitation of this study.

Conclusions

Results of this case-control study suggest that high plasma LDL-C levels were associated with a risk of LBD development, and higher fasting glucose level may also be an associated risk factor for LBD. However, high plasma HDL-C concentration may have a protective association in the development of LBD. Our study suggests that better lifestyle, diet, and medications geared toward the management of metabolic risk factors may lower the risk of LBD. Further studies to understand the mechanisms of blood cholesterol and blood glucose in the development of LBD are warranted.

Footnotes

ACKNOWLEDGMENTS

This work was funded by the Science and Technology Project of Tianjin Health and Health Committee (ZC20121), the Science and Technology Project of Tianjin Health and Health Committee (KJ20048), National Natural Science Foundation of China (82171182), Tianjin Key Medical Discipline (Specialty) Construction Project, and the Scientific Program of the Tianjin Education Committee (2016YD20).

Authors’ disclosures available online ().

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