Constipation and Sleep Disorders Point to Later Cognitive Decline, Study Suggests

Constipation and sleep behavior disorder are strongly associated with future decline in some cognitive measures in people — especially men — newly diagnosed with Parkinson’s disease, a study suggested.

Its researchers recommend early assessment of sleep disorders and constipation to help predict cognitive changes in later disease stages. 

The study, “Constipation and sleep behaviour disorder associate with processing speed and attention in males with Parkinson’s disease over five years follow-up,” was published in the journal Nature Scientific Reports. 

One of the most common non-motor symptoms of Parkinson’s is problems with the digestive (gastrointestinal) system, which occurs in up to 80% of patients, with constipation being recognized as a symptom in the early stages of the disease. 

Another early non-motor symptom is rapid eye movement sleep behavior disorder (RBD) — a condition in which people physically and vocally act out vivid dreams. 

However, whether constipation and RBD occurring in early disease stages are related to cognitive difficulties in later stages is unclear.

Identifying different factors that can contribute to cognitive dysfunction — on of the most frequent non-motor symptom in Parkinson’s — “is imperative given that [Parkinson’s] patients have a sixfold higher risk for developing dementia compared to the general population,” the researchers wrote.

Scientists at the University of New South Wales in Australia assessed the Parkinson’s Progression Markers Initiative (PPMI) database and analyzed the medical records of patients who had clinical assessments regarding constipation, RBD, and cognitive tests, and with five years of follow-up.

Of note, the PPMI is an ongoing multicenter observational clinical study of newly diagnosed Parkinson’s patients to identify clinical, imaging, and biological markers of disease progression. 

Their study included 360 adults — 238 men, 122 women — with a mean age of about 61 (39.2% were over the age of 65). At diagnosis (baseline), there were no demographic differences between these men and women, except that male patients had a higher body mass index (BMI, percentage of body fat based on height).

Overall, men also showed greater cognitive impairment at diagnosis than did women, as measured by the Montreal Cognitive Assessment (MoCA) for global cognitive function, the Symbol Digit Modalities Test (SDMT) for processing speed and attention, and the Hopkins Verbal Learning Test-Revised (HVLT-R) for verbal learning and memory.

At five years of follow-up, records were available for 281 patients, 189 men and 92 women. Again, female patients were found to have higher cognitive MoCA scores, SDMT scores, and better memory executive function and working memory as determined by Letter Number Sequencing (LNS) and semantic fluency scores.  

Older age at baseline was associated with greater cognitive impairment, measured by MoCA, SDMT, LNS, HVLT-R, and with worse constipation assessed by the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT) questionnaire. More years of education was associated with lesser cognitive impairment. 

There was a strong association between probable REM sleep behavior disorder (pRBD) at baseline, as measured by the REM Sleep Behaviour Disorders Screening Questionnaire (RBDSQ), and processing speed and attention (SDMT) in male patients. (Of note, pRBD was used as patients did not undergo sleep studies)

No other associations were found between RBDSQ or constipation and cognitive scores for either sex. 

Analyses of all male patients found a significant interaction between constipation and pRBD at baseline and processing speed and attention. Speed and attention scores among men who had both constipation and pRBD at diagnosis declined by 9.53 points more than did scores in those without these symptoms.

Excluding those with cognitive impairment (MoCA less than 26), neuropsychological tests evaluating processing speed and attention, memory executive function and working memory, and verbal learning and memory retention, were significantly associated with both constipation and pRBD in male Parkinson’s patients.

In women, pRBD was linked to overall cognitive scores (MoCA) and semantic fluency scores, while constipation was only associated with MoCA scores. 

An analysis found good predictive accuracy between a combined effect of constipation and pRBD for cognitive impairment, particularly with processing speed and attention. 

Adding demographic variables including age, years of education, and levodopa equivalent dose (the combined dose of Parkinson’s medications), strengthened the predictive ability of later cognitive decline in patients with constipation and pRBD.

“[Our] analysis showed that constipation and pRBD are strongly associated with worse cognitive outcomes in [Parkinson’s disease], while specific cognitive features appear to be more affected in males,” the researchers concluded. 

“Therefore, future work should address whether screening for constipation and sleep disorder might assist with early detection of cognitive impairment in men,” they added.