Portal de Periódicos da CAPES

Midlife cancer/diabetes and risk of dementia and mild cognitive impairment: A population‐based prospective cohort study in Japan

2019; Wiley; Volume: 73; Issue: 9 Linguagem: Inglês

10.1111/pcn.12905

1440-1819

Ryoichi Sadahiro, Norie Sawada, Yutaka Matsuoka, Masaru Mimura, Shoko Nozaki, Ryo Shikimoto, Atsushi Goto, Shoichiro Tsugane,

Cancer survivorship and care

The World Health Organization recognizes dementia as a public health priority and underscores the urgent need for society and physicians to understand the risk factors of dementia in order to provide opportunities for early prevention.1 While diabetes is a known modifiable risk factor for both dementia2 and cancer,3 the association between cancer and dementia remains uncertain. Population-based cohort studies have reported inconsistent risk levels for dementia among individuals with cancer.4, 5 We therefore conducted a cross-sectional survey using a prospective Japanese cohort to examine whether having cancer or comorbid cancer and diabetes from midlife increases the risk of physician-diagnosed dementia. This analysis builds on the framework of the Japan Public Health Center-Based Prospective Study.6 This study comprised 12 219 Japanese residents recruited in 1990 at age 40–59 years and the final analysis was performed among 1244 subjects (Fig. S1). This study was approved by the institutional review boards of the National Cancer Center Japan and Keio University School of Medicine and all participants provided written informed consent for participation. Cancer cases were identified from baseline until 31 December 2013 by active patient notification from the hospital. Cancer diagnoses were coded according to the International Classification of Diseases for Oncology, 3rd edition. Diabetes was identified using the highly validated self-administered questionnaire7 at baseline, 5 years, 10 years, and at the mental health screening and those who had diabetes at baseline were removed. Lifestyle information was surveyed at baseline. Trained neuropsychologists assessed cognitive function using the Mini-Mental State Examination, the Logical Memory I/II subtest of the Wechsler Memory Scale – Revised, the Clock-Drawing Test, and the Clinical Dementia Rating Scale. According to the Japan Alzheimer's Disease Neuroimaging Initiative project,8 for mild cognitive impairment (MCI), the cut-off point of the Wechsler Memory Scale – Revised Logical Memory II subtest was adjusted for education (2 for 0–9 years, 4 for 10–15 years, and 8 for >15 years). For dementia, the Mini-Mental State Examination cut-off point was set to 23. Subsequently, trained psychiatrists determined a final dementia diagnosis based on the DSM-IV. Patients not diagnosed with dementia were diagnosed with MCI if their memory function was less than the education-adjusted cut-off point or impaired enough to cause clinical problems. We defined cognitive decline (CD) as a diagnosis encompassing MCI and dementia. Logistic regression analyses were used to estimate odds ratios (OR) for the diagnosis of MCI, dementia, and CD among participants with versus those without cancer or diabetes. The multivariate model was adjusted for: age,2 sex,2 smoking history2 weekly alcohol consumption2 education2 physical activity2 and fish consumption.9 To evaluate the effect of comorbid cancer and diabetes, we estimated the OR for MCI, dementia, and CD for patients with (i) cancer, (ii) diabetes, and (iii) both cancer and diabetes, compared to patients with neither cancer nor diabetes. We considered two-sided P-values less than 0.05 to be statistically significant. During the study period of over 23 years, incident cancer and diabetes was ascertained in 162 and 116 participants, respectively. A total of 421, 60, and 481 participants were diagnosed with MCI, dementia, and CD, respectively. Participant characteristics are shown in Table S1. Although cancer was not significantly associated with MCI, dementia, or CD, diabetes was associated with an increased risk of dementia (OR, 2.60; 95% confidence interval [CI], 1.12–6.03) but not MCI or CD. Compared with those without cancer or diabetes, participants with comorbid cancer and diabetes showed heightened risk of MCI (OR, 3.42; 95%CI, 1.01–11.53), dementia (OR, 15.85; 95%CI, 2.39–105.31), and CD (OR, 3.66; 95%CI, 1.13–11.89). On the other hand, presence of diabetes without cancer was not significantly associated with dementia risk (Table 1). This is the first study to suggest that comorbid cancer and diabetes from midlife may increase the risk of MCI or dementia in later life with prospective long-term surveillance among middle-aged participants. Epidemiologic evidence suggests that diabetes increases cancer risk,3 resulting in increased likelihood of comorbid cancer and diabetes. In addition to the increased dementia risk associated with diabetes on the basis of insulin resistance, cancer and cancer therapies may also interfere with cognitive function via insulin resistance,10 providing a plausible etiology. A physician-directed interview for each participant is our strength. Limitations include relatively small sample size, potential selection bias in a population-based cohort, and not excluding MCI or dementia at baseline (aged 40–59 years). Our findings suggest that attention should be paid to cognitive decline when seeing patients who have comorbid cancer and diabetes. This work was supported by the National Cancer Center Research and Development Fund. The present work was also supported by the Practical Research for Innovative Cancer Control project (No. 18ck0106370h0002) from the Japan Agency for Medical Research and Development and Foundation for Promotion of Cancer Research in Japan. These funding sources had no role in any aspect of study design, data collection and management, data analysis and interpretation, or manuscript submission. We appreciate the great efforts of all staff members in the Saku area who assisted in conducting this survey. We particularly thank Yukiko Miyasaka and Shogo Hotta who contributed the management of mental health screening. R.S. has received grants from the SGH Foundation and Novartis Pharma. Y.J.M. has received speaker's honoraria from Morinaga Milk, Eli Lilly, and NTT Data and donations from Morinaga Milk within the past 3 years and is conducting collaborative research with Morinaga Milk. M.M. has received grants and/or speaker's honoraria from Asahi Kasei Pharma, Astellas Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, Fuji Film RI Pharma, Janssen Pharmaceutical, Kracie, Meiji-Seika Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Ono Yakuhin, Otsuka Pharmaceutical, Pfizer, Shionogi, Takeda Yakuhin, Tanabe Mitsubishi Pharma, and Yoshitomi Yakuhin within the last 3 years. The remaining authors declare no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.