Impact of constipation on progression of Alzheimer's disease: A retrospective study

• Published in: CNS neuroscience & therapeutics Vol. 28; no. 12; pp. 1964 - 1973
• Main Authors: Nakase, Taizen, Tatewaki, Yasuko, Thyreau, Benjamin, Mutoh, Tatsushi, Tomita, Naoki, Yamamoto, Shuzo, Takano, Yumi, Muranaka, Michiho, Taki, Yasuyuki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2022; John Wiley and Sons Inc
• Subjects: Alzheimer Disease - pathology; Alzheimer's disease; Atrophy; Chi-square test; Cognitive ability; Cognitive Dysfunction - pathology; cognitive function; Confounding (Statistics); Constipation; Dementia; Dementia disorders; Diabetes; Disease Progression; Hippocampus; Homocysteine; Humans; Hyperlipidemia; Hypertension; Laxatives; Magnetic Resonance Imaging; Multivariate analysis; Neurodegenerative diseases; Neuropsychological Tests; Neuropsychology; Normal distribution; Original; Patients; Questionnaires; Regression analysis; Retrospective Studies; Software; Substantia alba; Womens health; worsening; cognitive function; constipation; homocysteine; worsening; dementia; magnetic resonance imaging
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.13940

Background and Purpose In terms of the gut‐brain axis, constipation has been considered to be an important factor of neurodegenerative diseases, although the exact mechanism is still controversial. Herein, we aimed to investigate the contribution of constipation to the progression of dementia in a retrospective study. Methods Patients of Alzheimer's disease(AD) and amnestic mild cognitive impairment were consecutively screened between January 2015 and December 2020, and those of whom brain MRI and neuropsychological tests were performed twice were enrolled in this study. Participants were classified into with constipation (Cons[+], n = 20) and without constipation (Cons[−], n = 64) groups. Laboratory data at the first visit were used. Regression analysis was performed in MMSE, ADAS‐Cog, and the volumes of hippocampus on MRI‐MPRAGE images and deep white matter lesions (DWMLs) on MRI‐FLAIR images obtained at two different time points. Results The main finding was that the Cons[+] group showed 2.7 times faster decline in cognitive impairment compared with the Cons[−] group, that is, the liner coefficients of ADAS‐Cog were 2.3544 points/year in the Cons[+] and 0.8592 points/year in the Cons[−] groups. Ancillary, changes of DWMLs showed significant correlation with the time span (p < 0.01), and the liner coefficients of DWMLs were 24.48 ml/year in the Cons[+] and 14.83 ml/year in the Cons[−] group, although annual rate of hippocampal atrophy was not different between the two groups. Moreover, serum homocysteine level at baseline was significantly higher in the Cons[+] group than Cons[−] group (14.6 ± 6.4 and 11.5 ± 4.2 nmol/ml, respectively: p = 0.03). Conclusion There is a significant correlation between constipation and faster progression of AD symptoms along with expansion of DWMLs. Dementia patients with constipation showed higher serum homocysteine level and steeper cognitive decline along with faster expansion of brain white matter lesions than those without constipation. These findings suggest that chronic inflammatory response caused by constipation may lead to exacerbation of white matter lesions, resulting in the worsening of cognitive function.