Sex differences in neuropsychiatric symptoms of Alzheimer’s disease (AD) have been demonstrated in previous studies, and apolipoprotein E (ApoE)
Although Alzheimer’s disease (AD), as the most common dementia and the major cause for senile dementia, is usually characterized by cognitive impairments, neuropsychiatric symptoms affect most of patients with AD [
Apolipoprotein E (ApoE)
In this study, we investigated the interactions between gender and ApoE
All subjects were selected from consecutive patients diagnosed with AD in the baseline stage of China Cognition and Aging Study (China COAST), which is a national study on the mild cognitive impairment (MCI) and dementia based on hospital population [
All the participants in the present study underwent the following cognitive and neuropsychiatric assessments. The Mini-Mental State Examination (MMSE) [
The ApoE genotypes were determined using the restriction enzyme digestion approach previously described [
To summarize demographic data of our patients, we used
A total of 315 patients were included in our study, including 158 mild AD patients (CDR = 1) and 157 moderate to severe AD patients (113 with the CDR = 2 and 46 with the CDR = 3). The characteristics of our subjects are presented in Table
Characteristics of subjects and ApoE genotype frequencies.
Mild AD | Moderate to severe AD | |||||
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Male | Female |
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Male | Female |
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( |
( |
( |
( |
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Age | 71.0 (9.1) | 70.9 (10.0) | 0.967 | 69.0 (10.1) | 66.7 (10.6) | 0.156 |
Education (yr) | 9.2 (4.6) | 6.4 (5.4) |
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8.0 (4.6) | 4.8 (4.4) |
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MMSE | 17.9 (5.6) | 17.1 (4.9) | 0.294 | 12.8 (6.0) | 12.0 (5.1) | 0.803 |
ApoE genotype |
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56 (75.7) | 46 (54.8) |
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40 (61.5) | 55 (59.8) | 0.825 |
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7 (9.5) | 9 (10.7) | 0.794 | 6 (9.2) | 5 (9.1) | 0.365 |
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49 (66.2) | 37 (44.0) |
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34 (52.3) | 50 (54.3) | 0.801 |
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18 (24.3) | 38 (45.2) |
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25 (38.5) | 37 (40.2) | 0.825 |
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0 | 1 (1) | 1.000 | 1 (1.5) | 2 (2.2) | 1.000 |
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14 (18.9) | 34 (40.5) |
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19 (29.2) | 30 (32.6) | 0.653 |
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4 (5.4) | 3 (3.6) | 0.707 | 5 (7.7) | 5 (5.4) | 0.742 |
Table
The gender comparisons of the frequencies and scores of neuropsychiatric symptoms.
NPI items | Mild AD | Moderate to severe AD | ||||||||||
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All | All | |||||||||||
M | F | M | F | M | F | M | F | M | F | M | F | |
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Delusions | 16.2 | 26.2 | 12.5 | 21.7 | 27.8 | 31.6 | 33.8 | 39.1 | 37.5 | 41.8 | 28.0 | 35.1 |
0.7 ± 2.3 | 1.3 ± 4.1 | 0.5 ± 1.9 | 0.8 ± 1.9 | 1.3 ± 3.2 | 1.9 ± 5.8 | 2.1 ± 3.9 | 2.0 ± 3.7 | 2.3 ± 4.0 | 1.9 ± 3.4 | 1.8 ± 3.9 | 2.3 ± 4.3 | |
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Hallucinations | 10.8 | 15.5 | 8.9 | 8.7 | 16.7 | 23.7 | 24.6 | 26.1 | 25.0 | 21.8 | 24.0 | 32.4 |
0.3 ± 1.3 | 0.8 ± 2.6 | 0.2 ± 1.1 | 0.4 ± 1.5 | 0.6 ± 1.9 | 1.3 ± 3.4 | 1.3 ± 3.3 | 1.5 ± 3.3 | 1.4 ± 3.2 | 1.2 ± 3.0 | 1.2 ± 3.3 | 2.0 ± 3.9 | |
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Agitation/ |
20.3 | 20.2 | 17.8 | 17.4 | 27.8 | 23.7 | 32.3 | 35.9 | 37.5 | 30.9 | 24.0 | 43.2 |
0.7 ± 2.0 | 1.1 ± 2.8 | 0.7 ± 2.1 | 0.9 ± 2.5 | 0.8 ± 1.6 | 1.2 ± 3.2 | 1.5 ± 3.2 | 1.8 ± 3.4 | 1.5 ± 3.1 | 1.3 ± 3.1 | 1.4 ± 3.5 | 2.5 ± 3.9 | |
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Depression | 28.4 | 32.1 | 26.8 | 34.8 | 33.3 | 28.9 | 40.0 | 46.7 | 42.5 | 45.4 | 36.0 | 48.6 |
1.1 ± 2.4 | 1.7 ± 3.7 | 1.1 ± 2.6 | 1.5 ± 2.8 | 1.0 ± 1.7 | 1.9 ± 4.6 | 1.3 ± 2.6 | 1.9 ± 3.0 | 1.4 ± 2.9 | 1.9 ± 2.8 | 1.3 ± 3.0 | 2.0 ± 3.2 | |
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Anxiety | 18.9 | 19.0 | 19.6 | 19.6 | 16.7 | 18.4 | 35.4 | 45.7 | 32.5 | 43.6 | 40.0 | 48.6 |
0.7 ± 2.1 | 0.9 ± 2.6 | 0.8 ± 2.4 | 1.1 ± 2.8 | 0.4 ± 1.0 | 0.8 ± 2.4 | 1.8 ± 3.6 | 2.5 ± 3.7 | 0.7 ± 2.2 | 1.8 ± 3.0 | 2.4 ± 4.4 | 3.5 ± 4.7 | |
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Euphoria | 6.7 | 3.6 | 7.1 | 4.3 | 5.6 | 2.6 | 10.7 | 5.4 | 17.5 | 7.3 | 0 | 2.7 |
0.3 ± 1.2 | 0.1 ± 0.7 | 0.3 ± 1.3 | 0.2 ± 0.8 | 0.2 ± 0.9 | 0.1 ± 0.6 | 0.4 ± 1.7 | 0.3 ± 1.5 | 2.8 ± 4.0 | 0.4 ± 1.5 | — | 0.2 ± 1.3 | |
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Apathy | 36.5 | 27.4 | 35.7 | 32.6 | 38.9 | 21.1 | 52.3 | 52.2 | 50.0 | 52.7 | 56.0 | 51.4 |
1.7 ± 3.1 | 1.3 ± 2.9 | 1.7 ± 3.1 | 1.8 ± 3.5 | 1.8 ± 3.3 | 0.7 ± 1.5 | 3.3 ± 4.4 | 3.0 ± 4.2 | 1.0 ± 2.7 | 2.8 ± 4.1 | 4.0 ± 5.0 | 3.3 ± 4.3 | |
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Disinhibition | 5.4 | 10.7 | 5.3 | 13.0 | 5.6 | 7.9 | 12.3 | 27.2 | 15.0 | 16.4 |
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0.1 ± 0.5 | 0.5 ± 2.0 | 0.1 ± 0.6 | 0.7 ± 2.6 | 0.1 ± 0.2 | 0.2 ± 0.9 | 0.7 ± 2.2 | 1.2 ± 2.6 | 1.0 ± 2.7 | 0.6 ± 1.9 |
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Irritability | 14.7 | 16.7 | 16.1 | 8.7 | 11.1 | 26.3 | 20.0 | 30.4 | 22.5 | 16.4 |
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0.9 ± 2.6 | 0.6 ± 1.8 | 0.9 ± 2.7 | 0.2 ± 1.0 | 0.9 ± 2.6 | 0.9 ± 2.4 | 1.3 ± 3.3 | 1.7 ± 3.4 | 1.6 ± 3.7 | 0.9 ± 2.8 |
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Aberrant motor behavior | 13.5 | 16.7 | 12.5 | 21.7 | 16.7 | 10.5 | 24.6 | 38.0 | 35.0 | 34.5 | 28.0 | 43.2 |
0.6 ± 2.0 | 1.0 ± 2.8 | 0.6 ± 2.1 | 1.4 ± 3.2 | 0.6 ± 1.6 | 0.4 ± 2.0 | 1.7 ± 3.7 | 2.3 ± 4.0 | 1.6 ± 3.7 | 2.0 ± 4.1 | 2.0 ± 3.8 | 2.7 ± 4.3 | |
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Sleep behavior disturbances | 16.2 | 13.1 | 14.3 | 10.9 | 22.2 | 15.8 | 30.8 | 28.3 | 35.0 | 23.6 | 24.0 | 35.1 |
0.7 ± 1.9 | 0.9 ± 2.7 | 0.6 ± 1.7 | 0.7 ± 2.6 | 1.1 ± 2.6 | 1.1 ± 2.9 | 2.1 ± 4.0 | 1.6 ± 3.5 | 2.8 ± 4.8 | 1.2 ± 3.0 | 0.9 ± 2.1 | 2.3 ± 4.2 | |
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Appetite abnormalities | 8.1 | 11.9 | 8.9 | 13.0 | 5.6 | 10.5 | 16.9 | 15.2 | 17.5 | 12.7 | 16.0 | 18.9 |
0.3 ± 1.3 | 0.5 ± 1.8 | 0.3 ± 1.3 | 0.6 ± 2.0 | 0.3 ± 1.4 | 0.4 ± 1.5 | 1.3 ± 3.4 | 0.8 ± 2.4 | 1.4 ± 3.5 | 0.5 ± 2.0 | 1.2 ± 3.4 | 1.2 ± 2.9 | |
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Total | 74.3 | 70.2 | 69.6 | 71.7 | 88.9 | 68.4 | 81.5 | 90.2 | 82.5 | 90.9 | 80.0 | 89.2 |
8.1 ± 10.3 | 10.6 ± 16.7 | 7.8 ± 9.7 | 10.3 ± 13.0 | 9.1 ± 12.4 | 11.0 ± 20.3 | 18.6 ± 24.6 | 20.7 ± 21.4 | 19.7 ± 27.0 | 17.2 ± 18.9 | 16.8 ± 20.5 | 25.9 ± 24.0 |
Data are expressed as percentages of patients with individual symptoms and means of scores ± SDs.
Please note that the means with standard deviations of scores are represented the same as previous literatures, though the data are not normally distributed.
After controlling for age and educational duration, the logistic regression analyses demonstrated that the ApoE
In this study, we systematically investigated the sex differences in neuropsychiatric symptoms in mild AD and moderate to severe AD, and we analyzed the modifying effect of ApoE
Consistent with previous studies [
The underlying pathophysiological mechanisms of neuropsychiatric symptoms of AD are still not completely clear. However, increasing evidence has suggested that some pathological or neuroimaging biomarkers of AD were associated with neuropsychiatric disorders. Interestingly, it was also suggested that there was an interaction between sex and ApoE
There are some limitations in our study. Our subjects were chosen from neurology outpatients and therefore were not representative of the general population, though our study results might be of value in clinical setting. Furthermore, although the NPI we used is a validated and widely used instrument, it relies on the information from caregivers instead of patients.
This study supported the modifying effect of ApoE
The authors declare that there is no conflict of interests regarding the publication of this paper.
This paper was supported by the Specialized Research Fund for the Doctoral Program of Higher Education (20131107120002), CHINA-CANADA Joint Initiative on Alzheimer’s Disease and Related Disorders (81261120571), the National 973 Project Grant of China (2011CB504104), Scientific Promoting Project of Beijing Institute for Brain Disorders (BIBDPXM2014_014226_000016), Seed Grant of International Alliance of Translational Neuroscience (PXM2014_014226_000006), Key Medical Professional Development Plan of Beijing Municipal Administration of Hospitals (ZYLX201301), the National Science and Technology Major Projects for “Major New Drug Innovation and Development” of the Twelfth 5-Year Plan Period (2011ZX09307-001-03), the National Key Technology R&D Program in the Eleventh Five-Year Plan Period (2006BAI02B01), the Key Project of the National Natural Science Foundation of China (30830045), Beijing Municipal Science & Technology Commission (Z151100004015078), and Beijing Talents Fund (2014000021223ZK31).