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Cognitive function and activities of daily living in people affected by leprosy: A cross-sectional, population-based, case-control study
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.185410
Objectives: There has been controversy regarding whether or not people affected by leprosy have more cognitive dysfunction than healthy individuals. The purpose of this study was to assess cognitive functions and activities of daily living (ADL) in people affected by leprosy relative to a control population living in rural areas. Keywords: Activities of daily living; cognition; geriatrics; leprosy
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that has a predilection for skin and nerves.[1] The number of new leprosy cases steadily dropped from 2004 to 2011 as a result of sustained national programs and continued support from national and international partners. However, people affected by leprosy have been aging in developed countries and are faced with aging-related health problems, including cognitive decline. Physical impairment in cognitively normal older adults predicted future diagnosis of dementia of Alzheimer's type,[2] and baseline physical impairment was associated with cognitive decline in later life.[3] Leprosy patients could be expected to have cognitive dysfunction because they have a lot of physical disabilities.[4] In addition, long-term social isolation facilitates the development of dementia in the general population.[5],[6] Most people affected by leprosy live in social isolation for decades, despite the increasing acceptance and decreasing stigmatization of leprosy. Therefore, social isolation in people affected by leprosy could result in cognitive decline. In line with those expectations, some studies have reported that there is a higher prevalence of dementia in older leprosy patients than in healthy control groups.[7],[8] However, contrary to those results, there are some epidemiologic studies that have reported a low prevalence of dementia in leprosy patients.[9],[10],[11] To date, there has been a lot of controversy about the relationship between cognitive decline and leprosy.[7],[9],[10],[11] Few studies have investigated the effect of leprosy on activities of daily living (ADL) and cognitive function in aging populations. We aimed to ascertain cognitive function and ADL in people affected by leprosy and compare their results with those of healthy rural controls.
Participants Participants for this study were recruited from a cross-sectional house-to-house survey of people affected by leprosy, aged 37–94 (68.97 ± 9.57) years residing in Sorokdo, Korea. A total of 224 people affected by leprosy were surveyed for the study. People were eligible if they were affected by leprosy (multibacillary and paucibacillary), had completed treatment at the time of the interview (time interval from treatment completion to interview: 25 ± 5 years), were living in Sorokdo, were able to give consent, and were willing to participate. Each person affected by leprosy was matched for gender and age (within 1 year) with two healthy controls. The control population was selected from participants of the Namwon study.[12] The Namwon study is an ongoing prospective study designed to investigate the prevalence, incidence, and risk factors for chronic disease in a rural population. In 2007, a total of 10,667 (4201 men and 6466 women) among 33,068 residents that were reported in the 2005 census had completed the second session of investigation.[13] In the baseline test of the Namwon study, there were various questionnaires evaluating the physical activity and cognitive function of participants. We recruited a total of 448 control subjects from the participants of the Namwon study. Assessment of cognitive function and activities of daily living The people affected by leprosy and control participants were consistently evaluated for cognitive function and ADL. They performed the Korean Mini-Mental State Examination (K-MMSE),[14] Korean Dementia Screening Questionnaire (KDSQ),[15] and Seoul-Instrumental ADL (S-IADL) scales,[16] which were administered in-person by a clinical researcher under a neurologist's supervision.[17] The KDSQ consists of three divisions (i.e., global memory function, other cognitive function, and ADL), including 15 items that can detect early changes in cognitive decline for diagnosing dementia.[16],[17] Each item of the KDSQ is scored from 0 to 2, with a higher score indicating poorer function and a greater frequency. The S-IADL, which had been developed to assess patients' abilities to perform instrumental and social ADL, was shown to distinguish between healthy individuals and mild cognitive impairment in previous studies.[16],[18] The S-IADL consists of 15 items. The total scores of the S-IADL can range from 0 to 45, with lower scores indicating better function and higher scores indicating poorer performance. We also categorized items of the S-IADL into three subgroups (i.e., basic, high level, and autonomy) to clarify the pattern of ADL based on the Alzheimer's disease (AD) cooperative study scale for ADL.[19],[20] All KDSQ and S-IADL scores were confirmed through a careful review by two neurologists. Statistical analysis All statistical analyses were performed using the statistical software Statistical Package for Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) version 20. Differences in general characteristics and total scores of the K-MMSE, KDSQ, and S-IADL between people affected by leprosy and healthy controls were analyzed using chi-square test and Student's t-test. To control the possible effects of age, gender, and education, notwithstanding matching for age and gender between the two groups, we used a one-way analysis of covariance. This study was done to determine whether the people affected by leprosy showed a difference in their K-MMSE, KDSQ, and S-IADL scores when compared to controls. The results were considered statistically significant at P < 0.05. Ethics statement The Institutional Review Board of the Chonnam National University Hospital approved this study. All participants were informed in full about the purpose and methods of this study, and all of them gave written informed consent.
The mean age was 68.97 ± 9.57 years in people affected by leprosy and 68.39 ± 8.32 years in controls. The proportion of men was more than that of women in both groups. Educational year state was higher and the illiteracy rate was lower in controls than in people affected by leprosy. There was no significant difference in the proportion of high body mass index and apoE4 carrier between the groups [Table 1].
[Table 2] shows each item and total score of the K-MMSE, KDSQ, and S-IADL, adjusted for age, gender, and educational year in both groups. The K-MMSE score of people affected by leprosy was significantly higher than the K-MMSE score of controls (P = 0.022). This difference of K-MMSE scores between the two groups was maintained even with adjustments for age, gender, and educational year (P < 0.001). There was no significant difference in the KDSQ total score between the groups. However, on the three divisions of the KDSQ, people affected by leprosy had a lower score in the division for other cognitive function and a higher score in the division for ADL when compared to controls. On the S-IADL, people affected by leprosy performed significantly worse on 11 out of 15 activities relative to controls. People affected by leprosy were particularly more impaired in activities related to basic and autonomy ADL. However, there were no differences between the two groups on the high-level ADL.
In this cross-sectional, population-based, case-control study on cognition and ADL of leprosy patients, people affected by leprosy were found to have better cognitive function than healthy controls despite their worse ADL score. To the best of our knowledge, this is the first case-control study that compares the cognitive function and ADL between leprosy patients and healthy controls in Korea. People affected by leprosy had better cognitive function than healthy controls, and this relationship had not changed after adjusting for age, gender, and education level. People affected by leprosy had a lower score in the other cognitive function division of the KDSQ than controls. Although there was no difference in the KDSQ division related to memory between both groups, these results imply that cognitive function in people affected by leprosy is better than cognitive function in age- and gender-matched controls. These findings are consistent with some previous epidemiological studies, immunohistochemical studies, and meta-analyses indicating a lower frequency of dementia in leprosy patients.[9],[10],[11] However, there was a report that the prevalence of dementia in leprosy patients was higher than the expected prevalence of dementia in the overall population.[7] These conflicting studies on cognitive decline and the prevalence of dementia for patients with leprosy may be due to small sample sizes. According to the first epidemiological study on dementia in leprosy patients by McGeer, there was a clear decline in dementia in leprosy patients.[10] In this study, people affected by leprosy had better cognitive function in spite of having a worse ADL score than controls. The decreased ADL of people affected by leprosy is observed not only in the division of KDSQ related to ADL but also in the S-IADL. Particularly, most items of the S-IADL showed a worse score for people affected by leprosy than for controls. Our study had substantial inconsistencies because decreased basic ADL is often preceded by a decline in instrumental ADL in patients with early Alzheimer's dementia (AD) and mild cognitive impairment.[21] Good cognition in a poor ADL state is meaningful because physical activity usually has a positive effect on cognitive functions in older individuals.[22] We suggest that the decreased ADL in people affected by leprosy may be correlated with physical disability, rather than signaling decreased cognitive function. This may be because the high-level ADL of S-IADL appears to be well maintained in people affected by leprosy. Similarly, leprosy physical impairment grade was associated with dependence for IADL in a previous study.[23] Several potential mechanisms might explain better cognitive function in people affected by leprosy relative to controls. One possible explanation is the use of anti-leprosy drugs. Previous studies have suggested that lower amyloid plaque deposition and senile dementia prevention in people affected by leprosy might be due to the anti-inflammatory effect of anti-leprosy drugs.[9],[10],[11] Dapsone is one of the agents for anti-leprosy treatment and has been well known for providing antioxidants and neuroprotection.[11],[24],[25],[26] The contribution of inflammation in AD is still controversially discussed. However, it has been reported that markers related to immune response increase in AD. In addition, a reduced risk of developing AD has been shown in people using long-term nonsteroidal anti-inflammatory drugs.[20],[27],[28],[29],[30],[31] However, the duration of dapsone therapy (3.8 ± 1.2 years) was not related with the K-MMSE score in our study. Another possible explanation for why people affected by leprosy have better cognitive function than controls is because of community life. Individuals with a higher frequency of social contact have been found to have a significantly lower risk of dementia.[32] In our study, all people affected by leprosy had been living in a community around the hospital during the day. Except for sleeping at home, they shared routine activities together, including cultivation, leisure, and eating meals. In contrast to people affected by leprosy, Namwon residents belonging to the control group had been living in isolation because of the nature of their rural area. We speculate that close connectedness between members of society makes people affected by leprosy alert and keeps up the spirits of the aged. The significance of social contact has also been proven in a study on differences in the prevalence of dementia in the Japanese leprosarium group.[33] It is still not clear whether the better cognitive function in people affected by leprosy relative to controls is the result of anti-leprosy drugs, social contact, or leprosy itself. Therefore, more comprehensive studies are required to verify whether or not those factors have a protective effect on cognitive decline. This study has a number of limitations. First, as with all cross-sectional studies, we do not know about how the previous medication history may have affected the results of this study. However, we tried to control factors that could cause confusion in interpreting our results through a strict in-person survey, which included reviewing past medical history. Second, the scale for the evaluation of depression, which could affect our results, was not contained in this study. As mentioned above, cognitive function in older adults is especially known to be affected by social contact and emotional support. Therefore, we included a geriatric depression scale among the questionnaires for people affected by leprosy, but no instrument measuring the depression of control participants. We plan to evaluate these related questionnaires in the future.
People affected by leprosy have better cognitive function than healthy controls. Physical impairment resulting from leprosy is associated with greater dependence in instrumental ADL. Good cognition in a poor ADL state is worthwhile because physical impairment generally has negative effects on cognitive functions. We suggest that ADL impairment may be related to physical disability rather than decreased cognitive function. Further studies are needed to identify causal factors that provide a protective effect from cognitive decline in people affected by leprosy. Acknowledgments This study was supported by a grant from the Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning NRF-2014M3C7A1046041 (to BC Kim). Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Table 1], [Table 2]
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