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Keywords:

  • dementia;
  • sex;
  • major depressive disorder;
  • mild cognitive impairment;
  • subjective memory complaints

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Aim

The aim of this study was to investigate the association between subjective memory complaints (SMC) and sex.

Methods

We researched the prevalence of SMC in a sample of 394 participants who were at least 60 years of age (138 male and 256 female). We also administered the Mini-Mental State Examination (MMSE) and the Center for Epidemiologic Studies for Depression (CES-D) scale. A multiple logistic regression analysis, which included SMC in association with the MMSE or CES-D scores and other confounding factors, was performed to determine the influence of sex on SMC. A P-value < 0.05 was considered statistically significant.

Results

The durations of education of male participants were significantly higher than those of female participants. MMSE scores for female participants were significantly higher than those for male participants. There was no significant difference in CES-D scores between male and female participants. Twenty-four male participants and 72 female participants showed evidence of SMC. The incidence of SMC was more frequent in female participants than in male participants. In all participants, sex difference and CES-D score were significantly associated with SMC. In male participants, MMSE score was independently and significantly associated with SMC. Both in female participants and all participants, CES-D score was independently and significantly associated with SMC.

Conclusion

SMC varied by sex and were associated with the degree of cognitive impairment in male participants, while they were associated with depressive symptoms in female participants.

Many studies in clinical psychiatry have investigated the concept of subjective memory complaints (SMC) and suggest that the understanding of these complaints is of great relevance.[1] Some studies indicate that the presence of any type of SMC may indicate objective memory impairment or be predictive of future dementia.[2-4] In particular, difficulties following a group conversation or finding one's way around familiar streets may be associated with severe memory impairment.[5]

Recent studies suggest that SMC, in addition to being associated with dementia or cognitive impairment, are associated with depressive states or major depressive disorder (MDD). Fischer et al. studied the presence of SMC among participants with and without MDD and reported that the subgroup of patients with MDD had significantly more subjective memory complaints;[6] however, there were no significant differences between the two groups with respect to objective neuropsychological assessments. The decline in the self-evaluation of patients with MDD or the inhibition of thought may cause them to have SMC. Mowla et al. investigated the cognitive function of patients with MDD and revealed that there was no correlation between SMC and objective memory performance. Therefore, the meaning of SMC among patients with MDD in this study is questionable.[7]

In general, the prevalences of MDD, depressed mood and dementia, or cognitive impairment differ with sex. Previous studies have reported that women are more likely to develop MDD than men.[8-10] Gao et al. investigated the incidence of Alzheimer's disease and reported that the likelihood of women developing Alzheimer's disease relative to men is 1.56 (95% confidence interval, 1.16–2.10).[11] In addition, de Pedro-Cuesta et al. showed that the prevalence of Alzheimer's disease and dementia was higher in women.[12]

Thus, we hypothesized that there would be sex differences associated with SMC. However, no studies have specifically investigated this potential association. In this study, we investigated the association between the presence of SMC, cognitive impairment and depressed mood in a community-dwelling population and investigated the differential effect of sex on this association.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Participants

The study group consisted of 394 volunteers (more than 60 years old; 138 men and 256 women) who participated in the Iwaki Health Promotion Project in 2011. The participants were residents of Iwaki district, Hirosaki City, in northern Japan. Iwaki district is a stable community with a population of 12 220. The age and occupational distributions of this population are representative of a Japanese countryside community. Data collection for the present study and the project were approved by the Ethics Committee of Hirosaki University School of Medicine, and all subjects provided written informed consent prior to participating in the project. Demographic data (age, sex, and duration of education) and lifestyle factors (smoking and drinking) were obtained from self-questionnaires and interviews.

We excluded participants with a Mini-Mental State Examination (MMSE) score less than 24, because we investigated healthy subjects in the present study and a score less than 24 was defined as poor cognitive function.[13]

Assessments of cognitive function and SMC

The MMSE was given to all participants to measure their global cognitive status. This test assesses orientation to place and time, short-term memory, episodic long-term memory, subtraction, ability to construct a sentence, and oral language ability. The maximum score was set at 30, and poor cognition was defined as a score less than 24.[13]

Participants were asked the following question: ‘Have you been distressed by your forgetfulness?’ SMC were judged for each participant on the basis of their answer to this question.

Assessment of depression

The Japanese version of the Center for Epidemiologic Studies for Depression (CES-D) scale was also administered to all participants to measure their depressive status.[14] The questionnaire has been widely used to measure depressive symptoms in community populations, and it is also used as a screening tool for depression.[15] The CES-D is a 20-item, self-report scale that focuses on depressive symptoms within the week prior to administration of the questionnaire. The maximum score is set at 60, and higher scores are associated with depression. CES-D scores of 16 or higher have generally been thought to indicate clinically relevant depressive symptoms, including both minor or subthreshold depression and MDD.[16, 17]

Statistical analysis

Descriptive statistical analyses were performed to describe demographic and clinical variables. To compare how characteristics between groups differed by sex, the unpaired Student's t-test was used to analyze variables. A multiple logistic regression analysis of SMC in association with MMSE score, CES-D score and other confounding factors (age, duration of education and MMSE or CES-D score) was performed. The data were analyzed using spss for Windows 21 (IBM Japan, Tokyo, Japan). A P-value ≤ 0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Participant characteristics

The demographic data and scores for the MMSE and CES-D are presented in Table 1. The mean ages of male and female participants were 68.8 ± 6.7 and 68.7 ± 6.1 years, respectively. The duration of education was 11.1 ± 2.1 years for male participants and 10.5 ± 1.9 years for female participants. The duration of education of male participants was significantly higher than that of female participants. The average MMSE score was 28.0 ± 2.1 for male participants and 28.6 ± 1.8 for female participants. The MMSE scores of female participants were significantly higher than those of male participants. The average CES-D score was 10.6 ± 4.6 for male participants and 10.7 ± 5.8 for female participants.

Table 1. Demographic characteristics of subjects
 Total (n = 377)Men (n = 131)Women (n = 246)P-value
  1. *P < 0.005. **P < 0.01.

  2. Values are mean ± SD. The Student's unpaired t-test was used to evaluate the differences between men and women.

  3. CES-D, Center for Epidemiologic Studies for Depression; MMSE, Mini-Mental State Examination; SMC, subjective memory complaints.

Age68.7 ± 6.368.8 ± 6.768.7 ± 6.10.868
Duration of education (years)10.7 ± 2.011.1 ± 2.110.5 ± 1.90.012*
SMC25.4% (n = 96)18.3% (n = 24)29.2% (n = 72)0.015*
MMSE28.4 ± 1.928.0 ± 2.128.6 ± 1.80.005**
CES-D10.7 ± 5.410.6 ± 4.610.7 ± 5.80.881

Twenty-four male participants (18.3%) and 72 female participants (29.2%) had SMC. The rate of participants who reported SMC was significantly higher in female participants than that in male participants.

Influence to subjective memory complaints

Multiple logistic regression analysis was performed for all participants and each sex to assess the influence of MMSE and CES-D score on SMC.

Table 2 provides details of multiple logistic regression analysis for SMC in association with the MMSE and CES-D score and other confounding factors in all participants. In all participants, sex difference and CES-D score was significantly associated with SMC.

Table 2. Multiple logistic regression analysis for subjective memory complaints in entire subjects
VariablesRegression coefficient (β)Standard errorOdds ratio95% confidence intervalP-value
  1. *P < 0.05. **P < 0.01.

  2. CES-D, Center for Epidemiologic Studies for Depression; MMSE, Mini-Mental State Examination.

Sex0.6260.2841.8701.071–3.2670.028*
Age0.0100.0211.0100.969–1.0540.627
Duration of education (years)−0.0380.0700.9360.840–1.1050.591
MMSE−0.0590.0660.9420.827–1.0730.371
CES-D0.0840.0251.0881.036–1.1430.001**

Table 3 provides details of multiple logistic regression analysis for SMC in association with the MMSE and CES-D score and other confounding factors in male participants. In male participants, only MMSE score was significantly associated with SMC.

Table 3. Multiple logistic regression analysis for subjective memory complaints in male subjects
VariablesRegression coefficient (β)Standard errorOdds ratio95% confidence intervalP-value
  1. *P < 0.05.

  2. CES-D, Center for Epidemiologic Studies for Depression; MMSE, Mini-Mental State Examination.

Age0.0420.0391.0430.967–1.1250.271
Duration of education (years)0.0380.1251.0380.813–1.3260.763
MMSE−0.2840.1210.7520.593–0.9540.019*
CES-D0.0010.0580.9990.891–1.1200.987

Table 4 provides details of multiple logistic regression analysis for SMC in association with the MMSE and CES-D score and other confounding factors in female participants. In female participants, only CES-D score was significantly associated with SMC

Table 4. Multiple logistic regression analysis for subjective memory complaints in female subjects
VariablesRegression coefficient (β)Standard errorOdds ratio95% confidence intervalP-value
  1. **P < 0.01.

  2. CES-D, Center for Epidemiologic Studies for Depression; MMSE, Mini-Mental State Examination.

Age−0.0110.0260.9890.939–1.0410.665
Duration of education (years)−0.0900.0850.9140.773–1.0800.289
MMSE0.0650.0861.0670.901–1.2640.453
CES-D0.1060.0301.1121.049–1.1790.000**

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

The results of this study showed that SMC are differentially associated with cognitive impairment or depressive symptoms on the basis of sex. In male participants, SMC were associated with actual cognitive impairment, while in female participants, SMC were associated with depressive states. This is the first study to show a sex difference with regard to the clinical meaning of SMC. These findings indicate that when patients have SMC, clinicians should pay more attention to cognitive impairment in men and depressive status in women. Odds ratios (OR) of the significant variables were relatively low, but sex showed the highest OR (1.870) in all participants. Thus, we should particularly consider the sex of patients who have SMC.

Previous studies have reported that SMC are related to actual cognitive impairment.[3, 4] Clarnette et al. indicated that cognitive function, as assessed using MMSE scores, in subjects with SMC (n = 97) was significantly lower than that in controls (n = 38).[3] In addition, Benito-Leon et al. investigated SMC in a large sample (1073 vs 1073) and reported that some measures of cognitive function were significantly different between groups, while other measures of cognitive function were not different between subjects with and without SMC.[4] However, there was no information regarding the impact of sex on these differences. In this study, there was no significant association between SMC and actual cognitive impairment in the sample population.

An association between SMC and depressive mood has been reported in a previous small study.[6] Scores on several SMC measures, although not all measures, for depressed patients were significantly higher than those for controls. However, this study did not include a description of the effect of sex on this difference or the number of male and/or female subjects. In the present study, there was a significant association between SMC and CES-D scores, not only in female participants but also in the entire sample population. This result may have been influenced by the fact that most of the subjects with SMC in this study were female.

We are unable to explain why the meaning of SMC differs by sex; however, sex differences in character or temperament may influence the results.[18] Men may objectively recognize their actual cognitive impairment and thus accurately report SMC. On the other hand, women may interpret minor forgetfulness as severe symptoms of dementia and may become depressed, or women with depressive symptoms may be more likely to have SMC than men.

The MMSE scores of female participants were significantly higher than those of male participants. The scores of MMSE subscale 1 (P = 0.045) and 4 (P = 0.020) of female participants were significantly higher than those of male participants. A lower subscale 1 score indicates temporal orientation disturbance and a lower subscale 4 score indicates attention and calculation disturbance. The difference of lifestyle between men and women might lead to a difference in the score of the subscale. In the Japanese countryside community, men go to work every day and their lifestyle tends to be the same as usual. Women do housework and grocery shopping, so they have to calculate frequently and be aware of the dates of the garbage days. Such habits might lead to differences in the MMSE subscales, but it is unclear whether these lead to SMC.

Mild cognitive impairment (MCI) is one of the most important themes in neuropsychiatric research that is related to dementia and depression. Modrego and Ferrandez reported that MDD increases the likelihood of the development of Alzheimer's disease in patients with MCI.[19] Although MDD is an independent risk factor for dementia,[20, 21] depressive symptoms are the prodromal symptoms of cognitive decline.[22, 23] Palmer et al. reported that among individuals with MCI and no dementia, 11% remained stable and 25% improved compared to baseline after 3 years of follow-up;[24] in particular, the group demonstrating improvement may have consisted of individuals with MDD who subsequently recovered from the condition. Therefore, the presence of MDD should be considered for patients who present with MCI.

There are some limitations to the current study. First, we used only one question (‘Have you been distressed by forgetfulness?’) to assess the presence of SMC. Some studies have used a subjective memory complaints scale to evaluate the presence of SMC;[2, 25, 26] however, the present study did not include an analysis of the quality of SMC. Second, we studied a general, community-dwelling population. It is unclear whether our data are generalizable to patients visiting hospitals or clinics for SMC. Further studies are needed to further clarify the influence of sex on subjective memory complaints in patients. Third, this study was conducted at only one site; therefore, our results could have been influenced by the culture of this region of Japan. Further research in other countries or of other races is needed to confirm our preliminary results. Fourth, there is no information about the physical diseases and the impairment of activities of daily living. These could influence the cognitive function and lead to depressive symptoms, and such information might change the results of the present study.

In conclusion, this study showed that SMC are differentially associated with cognitive impairment or depressive symptoms on the basis of sex. In male participants, SMC were associated with actual cognitive impairment, while in female participants, SMC were associated with depressive states. Further studies are needed to confirm our preliminary results.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

The authors would like to thank all of their coworkers on this study for their skillful contributions to the collection and management of the data. The authors declare that they have no competing interests.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
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