A cross-sectional study of inpatients with late stage of dementia in Southeast China and the associations between biochemical parameters and apolipoprotein E genotypes
Clinical Interventions in Aging
A cross-sectional study of inpatients with late stage of dementia in southeast China and the associations between biochemical parameters and apolipoprotein e genotypes
Bin Jiang 0
Xue-Ping Zhang 0
Mei-Fang Chen 0
Zheng Wang 0
Ming-Xue Zhao 0
Bin-hua Chen 0
0 Bin-hua Chen The seventh People's hospital of hangzhou, Mental health Center of Zhejiang University school of Medicine , no 305 Tianmushan road, hangzhou 310013, People's republic of China Tel
PowerdbyTCPDF(ww.tcpdf.org) Background: The purpose of this study was to analyze the disease distribution of patients in the late stage of dementia through a cross-sectional investigation and to clarify the association between apolipoprotein E (APOE) genotypes and the serum levels of total cholesterol, total triglycerides, and blood glucose in the late-stage Alzheimer's disease (AD) patients. Methods: Patients who were in the late stage of dementia in a mental health center were enrolled in this study. A broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. The APOE genotype was determined by the multiplex amplification refractory mutation system polymerase chain reaction. The association between APOE genotype and the blood level of biochemical parameters was studied. Results: A total of 155 patients were enrolled in this study. The majority of patients had AD (67.8%), followed by vascular dementia (15.5%), mixed dementia (9%), and others (7.7%). The APOE ε4 allele frequency was significantly different in the different groups. The serum level of total cholesterol (TC) in APOE ε4 carriers was higher than in non-carriers (P,0.05). No statistically significant differences were found in the blood glucose and triglycerides (TG) levels between these two groups. Conclusion: To our knowledge, this is the first paper to study the characteristics of late-stage dementia in hospital patients in Southeast China. We found that the disease distribution was quite consistent with previous prevalence studies. Moreover, we found that the serum level of TC was higher in APOE ε4 carriers group. However, no association was found between the APOE ε4 allele and serum levels of glucose, TC and TG in the late stage of AD.
Alzheimer's disease; APOE; glucose; cholesterol; triglycerides
open access to scientific and medical research
1Department of n eurology and
research Center of n eurology,
The s econd Affiliated h ospital
of Zhejiang University s chool of
Medicine, hangzhou, 2Department
of n eurology, The First Affiliated
hospital of Xiamen University,
Xiamen, 3The s eventh People’s
hospital of hangzhou, Mental health
Center of Zhejiang University s chool
of Medicine, h angzhou, People’s
republic of China
*These authors contributed equally
to this work
Dementia is a broad battery of brain diseases that cause a long-term cognitive decline
and is to affect a person’s daily living. Alzheimer’s disease (AD) is the most common
cause of dementia, which is characterized by irreversible decline of memory and other
cognitive domains. More than 44 million individuals are afflicted with AD nowadays,
and the prevalence is expected to increase to 115.4 million by 2050.1 Many patients
gradually lost the ability to work due to decline in cognitive abilities and finally lost the
capability of physical self-maintenance in the late stage of the disease. In the People’s
Republic of China, many patients who are in the late stage of dementia are sent to
mental disorder hospitals. In our opinion, these patients provide a very good resource
to study the characteristics of dementia. However, there was no existing study about
Clinical Interventions in Aging 2018:13 159–163 159
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the late stage of dementia patients in the People’s Republic
of China. Therefore, one of our aims is to analyze the
distribution of patients in the late stage of dementia through a
The apolipoprotein E (APOE) gene encodes a glycoprotein
that plays an important role in central nervous system (CNS)
lipid homeostasis during neuronal growth and in nerve
regeneration. There are three major APOE isoforms: ApoE ε2,
ApoE ε3 and ApoE ε4. The ε4 allele of APOE was believed
to be a detrimental factor for sporadic Alzheimer’s disease
(SAD).2,3 It has been reported that the ε4 allele is associated
with a higher level of serum total cholesterol (TC) as well
as with low-density lipoprotein cholesterol.4–6 Besides,
previous studies also found that the ε4 allele affected cerebral
glucose metabolism and resulted in increased deposition of
Aβ.7,8 However, most of these studies were performed in the
Caucasian population with controversial results and there
has been no study about the association between the APOE
.rvdoepww ll.syeuon tgheenloattyepsetaagnedotfhdeelmeveenltsiaoifnsAerDumpabtiieoncthse. mInicthael pcuarraremnettsetursdiyn,
//:sw ano we analyzed the proportion of AD among these dementia
h pe patients and studied the associations of APOE genotypes
with the levels of TC, total triglycerides (TG) and the blood
glucose of the AD patients.
Methods and materials
All the patients were enrolled at the Mental Health Center of
Zhejiang University School of Medicine in Hangzhou from
March 2014 to July 2016. The disease duration was more than
5 years (mean 10.26 years, standard deviation 3.974 years).
The Diagnostic and Statistical Manual of Mental Disorders,
4th Edition,Text Revision (DSM-IV-TR) and National
Institute of Neurological and Communicative Disorders and
Stroke-Alzheimer’s Disease and Related Disorders
Association (NINCDS-ADRDA) criteria were applied to obtain the
diagnosis of probable clinical AD. Moreover, the criterion9 for
dementia with Lewy bodies (DLB), the criterion10 for
frontotemporal dementia (FTD) and the NINDS–AIREN criteria for
vascular dementia (VaD) were applied to obtain the diagnosis
of non-SAD forms of dementia.9–11 Furthermore, the routine
medical examination, neurological examination,
neuroimaging tests (CT or MRI), the Mini-Mental State Examination
(MMSE), the Activity of Daily Living Scale (ADL) and
the Clinical Dementia Rating (CDR) were applied to
evaluate each participant. The exclusion criteria were described
in our previous study.12 Briefly, patients with depression,
mental retardation and other psychiatric disorders;
hydrocephalus; syphilis; cognitive disorders caused by head trauma;
poisoning; Huntington’s disease; and severe heart, lung or
kidney disease were excluded. This study was approved by
the ethics committee of the Mental Health Center of Zhejiang
University School of Medicine. All participants were Han
people, and written informed consents were obtained from
the patients or the guardians of the patients.
genotyping of APOe
Genomic DNA was extracted from peripheral blood using a
Blood Genomic DNA Extraction Kit (Tiangen, People’s
Republic of China). The primer for genotyping of APOE included
GGACATGGAGGACGTTC-3′) and a common primer
(5′-GTTCAGTGATTGTCGCTGGGCA-3′). The multiplex
amplification refractory mutation system polymerase chain
reaction was applied to determine APOE genotypes.13
Measurement and analysis serum levels
of TC and Tg
Serum TC, TG and fasting blood glucose levels were
determined on the same auto-analyzer (Olympus, Tokyo,
Japan, AU640). The serum TC level .5.7 mmol/L, TG
level .1.8 mmol/L and fasting blood glucose .6.1 mmol/L
were defined as hypercholesterolemia, hypertriglyceridemia
and hyperglycemia, respectively.
The APOE ε4 allele frequency and ε4ε4 genotype were
compared using the chi-square test, and the age and the
MMSE scores were assessed by one-way analysis of variance
in the different groups. The mean value of glucose, TC and
TG were assessed by independent-samples t-test in the
different groups. Logistic regression analyses were performed to
evaluate the possible associations between APOE genotype
and the biochemical parameters. Covariates were age, history
of hypertension and history of smoking and alcohol drinking.
All statistical analyses were performed by the SPSS version
15.0 software (SPSS Inc., Chicago, IL, USA). P-values less
than 0.05 were considered statistically significant.
The disease distribution and APOe
A total of 155 patients who were in the late stage of dementia
were enrolled in this study. In our study cohort, the majority
of the subjects were patients with AD, which accounted for
67.8% of total subjects. In all, 15.5% and 9% of patients
had VaD and mixed dementia, respectively. The remaining
7.7% consisted of subjects with FTD, DLB and patients who
were very difficult to classify. The detailed disease
distribution and APOE genotype are shown in Table 1. Age, sex,
the ADL and the ε4ε4 genotype did not have statistically
significant differences. The MMSE scores, the CDR and the
APOE ε4 allele frequency were significantly different in the
Association between the serum levels
of biochemical parameters and APOe
genotypes in AD patients
The characteristics of AD patients with different APOE
isoforms are shown in Table 2. The serum level of TC in
APOE ε4 carriers was higher than in non-carriers. No
statistically significant differences were found in the blood glucose
and TG levels between these two groups. No correlations
were found between the APOE ε4 carrier status and serum
levels of glucose (adjusted odds radio 1.179, 95% confidence
interval 0.334–4.168, P=0.798), TC (adjusted odds radio
2.028, 95% confidence interval 0.392–10.502, P=0.400)
and TG (adjusted odds radio 1.238, 95% confidence interval
0.518–2.958, P=0.630). Details are shown in Table 3.
With the increase in human lifespan, the age-related
neurodegenerative diseases have become the biggest challenges
of the 21st century. Dementia, including AD, is one of the
most devastating neurodegenerative disorders that affect
millions of people annually. In the People’s Republic of China,
many late-stage dementia patients are sent to mental disorder
hospitals due to loss of ability of physical self-maintenance
and mental confusion. In this study, we analyzed the disease
distribution of patients who were in the late stage of dementia
in a mental disorder hospital in Southeast China. We found
that the most common type of dementia was AD (67.8%),
followed by VaD (15.5%) and mixed dementia (9%), while
FTD and DLB were comparatively rare in our study cohort.
These results were quite consistent with previous studies.
For example, researchers studied the disease distribution of
1,194 cases of dementia in patients aged above 70 years in
Spanish populations and found that 707 (59.2%) had AD
and 238 (19.9%) had VaD.14 Besides, in Italy, a prevalence
study of dementia in an elderly rural population found that
AD accounted for 64%, VaD for 27% and other dementia
diseases for 9%.15 Moreover, in a meta-analysis of prevalence
of dementia in developing countries, AD was reported to
account for 60%, whereas VaD accounted for about 30%.16
Although these were all results from prevalence studies and
our study was a cross-sectional study of inpatients of
latestage dementia, the results were comparable. As a result, we
Table 3 effects of APOE ε4 allele on biochemical parameters
Biochemical OR 95% CI P-value
Blood glucose 1.179 0.334–4.168 0.798
Total cholesterol 2.028 0.392–10.502 0.400
Total triglycerides 1.238 0.518–2.958 0.630
Note: logistic regression model was adjusted for age, history of hypertension,
alcohol use and smoking use.
Abbreviations: APOE, apolipoprotein E; OR, odds ratio; CI, confidence interval.
.rvdoepww ll.syeuon in the development of AD.
higher serum level of total cholesterol was associated with
APOE ε4 carriers in a cognitively normal aging
population.18 Previous studies reported the APOE ε4 status had an
influence on the level of low-density lipoprotein cholesterol
and high-density lipoprotein cholesterol.19 In our study,
the serum level of TC was higher in the APOE ε4 carriers,
compared with the non-APOE ε4 carrier group. This result
suggested that the APOE protein might be involved in a
specific pathophysiologic mechanism of lipid metabolism
Lately, it has been reported that dysregulation of glucose
metabolism in the brain is a risk factor for mild cognitive
impairment and AD.20,21 Besides, one study suggested that
high serum glucose levels may worsen cognitive function
as well as accelerate the cognitive decline.22 Some studies
reported that APOE ε4 modulates regional cerebral glucose
metabolism and affects the signal of glucose and amyloid
metabolic pathways in the pathogenesis of AD.23,24 Another
research indicated that the mean prevalence of PET
amyloid positivity is 95% in APOE ε4-positive AD patients.25
In addition, previous studies have reported that the APOE
ε3 genotype had higher glucose levels than the APOE
ε4 genotype.26 Furthermore, APOE ε4 carrier status and
elevated blood glucose were associated with more severe
AD pathology.27 Overall, all these studies have
demonstrated that the APOE protein plays an important role in
the pathogenesis of late-onset AD, not only in the aspect
of Aβ deposition but also in the aspect of cerebral glucose
metabolism. However, in our study, we were unable to find
a positive association between the level of blood glucose
and APOE genotypes.
There are some limitations of our study. First and most
important of all, the sample size was comparatively small.
It will be necessary to replicate these study results in a large
population. Besides, we have only analyzed some basic
biochemical parameters in this current study. A further
extension of these parameters, for example, the level of glucose
intolerance and insulin resistance, will be more accurate
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postulate that inpatients in the late stage of dementia are a
small focus group of these disease groups, which makes it a
To the best of our knowledge, this is the first paper to study
good resource for investigating this disorder.
the characteristics of late-stage dementia in hospital patients
In our study results, the APOE ε4 allele frequency
difin Southeast China. We found that the disease distribution
fered significantly between the four subgroups, which was
was quite consistent with previous prevalence studies.
Moreconsistent with previous studies in Chinese AD patients.17
over, we found that the serum level of TC was higher in the
The APOE protein is believed to play an important role
APOE ε4 carrier group. However, no association was found
in CNS lipid homeostasis during neuronal growth and in
between the APOE ε4 allele and serum levels of glucose, TC
nerve regeneration. Recently, one study indicated that a
and TG in the late stage of AD.
This work was supported by grants from the National Natural
Science Foundation (81500908).
The authors report no conflicts of interest in this work.
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