Disrupted rest and activity patterns could be an early indicator of Alzheimer's

Scientists from the US have found a link between certain biological fingerprints thought to indicate early stages of Alzheimer's and sleep disturbances. Their findings are published today in JAMA Neurology.
Links between poor sleep and dementia have been known of for some time but teasing out the precise cause and effect relationship is difficult – does poor sleep contribute to developing dementia, or is it that poor sleep is an early indicator of the condition?

04 feb 2018--To try to understand this relationship, a team of researchers from Washington University studied a group of 186 volunteers, using wearable activity monitors (actigraphy) day and night to measure periods of rest and activity as this group went about their normal daily lives in their homes. The study participants were all over the age of 45 (mean age, 66), and did not have any problems with memory or thinking. Participants (155 people) had donated samples of spinal fluid, in which the researchers measured the levels of two Alzheimer's proteins, tau and amyloid. Some participants (142 people) had also undergone specialised brain scans to measure the level of amyloid in their brain, called a PiB-PET scan.
The researchers found that increasing age was linked with decreased sleep quality, shown by a fragmenting of normal rest-activity patterns, such as increased napping during the day and being awake during the night. Looking at the brain scans, the researchers set a level to determine which scans showed amyloid build-up, finding 26 people showed amyloid high levels of amyloid in their brains and 116 people did not.
When they compared the two groups, the scientists found that people with amyloid build-up showed more fragmented rest-activity patterns, even when age and sex were taken into account. Similarly, people with an increased ratio of tau to amyloid in their spinal fluid, indicative of early Alzheimer's changes, were also found to have fragmented rest-activity patterns.
Dr. David Reynolds, Chief Scientific Officer at Alzheimer's Research UK, said:
"Research has faced a bit of a chicken and egg situation when looking at the links between sleep and dementia. While we know that people with Alzheimer's experience disturbed sleep patterns, whether this contributes to the disease or is an early consequence has been unclear. This study observes changes in daily rest and activity patterns at an early stage, where people are showing signs of Alzheimer's in the brain but before symptoms begin.
"In the past, studies have used sleep diaries to look at the links between sleep and health conditions, but the development of wearable activity monitors is helping researchers gain deeper and more accurate insight into the factors at play. We can't conclude from this study that napping more during the day can lead to dementia, and future studies will need to follow volunteers over longer periods of time. Studies like this add new pieces to the jigsaw of our understanding, and could lay the groundwork for new ways to detect the condition earlier, focusing on a range of factors and not just memory and thinking tests."


Provided by Alzheimer's Research UK

Cholesterol-lowering drug linked to sleep disruptions

American Heart Association meeting report
ORLANDO, Nov. 7 — A cholesterol-lowering drug appears to disrupt sleep patterns of some patients, researchers reported at the American Heart Association’s Scientific Sessions 2007.
“The findings are significant because sleep problems can affect quality of life and may have adverse health consequences, such as promoting weight gain and insulin resistance,” said Beatrice Golomb, M.D., lead author of the study and an associate professor of medicine and family and preventive medicine at the University of California at San Diego School of Medicine.
In the largest study of its kind, researchers compared two types of cholesterol-lowering drugs called statins — simvastatin, which is lipophilic (soluble in fats), and pravastatin, which is hydrophilic (soluble in water).
Because simvastatin is fat soluble it can more readily penetrate cell membranes and cross the blood brain barrier into the brain. The brain controls sleep, and many of the brain’s nerve cells are wrapped in a fatty insulating sheath called myelin.
“The results showed that simvastain use was associated with significantly worse sleep quality. A significantly greater number of individuals taking simvastatin reported sleep problems than those taking either pravastain or the placebo,” Golomb said. “On average, the lipophilic statin had a greater adverse effect on sleep quality.”
In past studies and case reports, some people on statins reported having insomnia or nightmares.
“Several small studies were done early on, including those focused on lipophilic versus hydrophilic statins,” Golomb said. “Most (researchers) didn’t see a difference in sleep, but they had short durations of follow-up and enrolled just a handful of people — often fewer than 20, which was not enough to see a difference unless it was very large.
“One of these studies did report a significant difference between pravastatin and simvastatin. But without more and bigger studies, an effect was not considered to be established.”
In this study, researchers tested 1,016 healthy adult men and women for six months in a randomized, double-blind, placebo-controlled trial using simvastatin, given at 20 milligrams (mg), pravastatin at 40 mg, or a placebo. They assessed outcomes with the Leeds sleep scale, a visual analog scale of sleep quality, and a rating scale of sleep problems. Both scales were measured before and during treatment.
“Those who reported developing much worse sleep on study medication also showed a significant adverse change in aggression scores compared to others,” Golomb said “We should also point out that although the average effect on sleep was detrimental on simvastatin, this does not mean that everyone on simvastatin will experience worse sleep.”
Researchers did not include patients with heart disease or diabetes due to concerns about assigning these people to placebos.
“Patients taking simvastatin who are having sleep problems should consult with their doctor,” Golomb said. “Sleep deprivation is a major problem in a minor number of people.”

Anxious Personality Predisposes to Sleep Disturbance After Major Stress

TURKU, Finland, Nov. 1 -- People who tend to experience daily life as highly stressful may be more likely to develop sleep problems when traumatic events occur, researchers found.However, the 1.5- to three-fold increased risk may persist only for the first months after a stressful event, such as divorce or family illness, reported Jussi Vahtera, M.D., of the Finnish Institute of Occupational Health here, and colleagues in the November 1 issue of the journal SLEEP.
Action Points
Explain to interested patients that their daily experience of anxiety may impact their sleep after a major stressful event.
Inform patients that the study did not look at whether treating an ingrained tendency toward anxiety or sleep disturbance could impact the effects of a major stressful life event.
These findings from a large, population-based study provide prospective evidence that people who are anxious by nature are predisposed to sleep disturbances, the researchers said.
They analyzed data from the longitudinal Health and Social Support study with a representative sample of the Finnish population. The analysis included 19,199 respondents who completed a survey both at baseline in 1998 and five years later.
At baseline, participants fell into four age groups -- 20 to 24, 30 to 34, 40 to 44, or 50 to 54 -- and 13% reported sleep disturbances. At follow-up, 11% reported new-onset sleep disturbances.
Liability to anxiety, indicated by a general feeling of stressfulness (as measured by the Reeder stress inventory) and symptoms of sympathetic nervous system hyperactivity, was strongly linked to disturbed sleep, the researchers said.
Men and women with the highest levels of general stress on a day-to-day basis were 2.4 times more likely to develop new-onset sleep disturbances compared with those in the lowest quartile (95% confidence interval 2.0 to 2.7). For symptoms of sympathetic nervous system hyperactivity, the odds of developing sleep disturbances were 2.2 times higher for those in the highest quartile than for those in the lowest quartile (95% CI 1.9 to 2.5).
Anxiety also increased risk for persistent sleep disturbances.
Respondents with the most symptoms of sympathetic nervous system hyperactivity were 1.5 times more likely to have sleep disturbances that persisted from baseline through five-year follow-up than those in the lowest quartile of this measure of anxiousness (95% CI 1.2 to 1.8).
Stressful events appeared to trigger problems sleeping, particularly for those who reported a high liability to anxiety.
From baseline to six months before the five-year follow-up, 13,180 participants reported a severe stressful event, such as death or illness in the family, divorce or separation, financial difficulties, or emotional, physical, or sexual violence. Participants who reported events related to changes in their health, which could impact sleep, were excluded.
Another 5,642 patients had a major stressful event in the six months before the follow-up. Among them, 71% experienced one event, 20% reported two events, and the remainder had up to eight events.
For participants who did not have pre-existing sleep problems, cumulative exposure to stressful events linearly increased with risk of sleep disturbances and was about double the risk of unexposed participants whether the events were recent or not.
The association did not appear to be entirely explained by controlling for anxiety and other predictors of sleep disturbances, which reduced the associations by no more than 33% to 39%, the researchers said. Nor were the associations explained by depression.
Death or illness in the family, divorce, and financial difficulties were independent predictors of new-onset sleep disturbances over the longer term, whereas financial difficulties were independently associated with sleep over the shorter term.
For men and women with pre-existing sleep disturbances at baseline, stressful life events were also associated with a 1.6- to two-fold increase in risk of persistent sleep problems at the five-year follow-up, "but only if the event had occurred within six months," the researchers noted.
Anxious people who experienced stressful events had the greatest likelihood of sleep disturbance over the short term.
For men who reported a negative life event, the odds were 3.11 times higher for those with a high general feeling of stressfulness (95% CI 1.90 to 5.10) and 2.88 times higher for those with sympathetic nervous system hyperactivity (95% CI 1.69-4.91) than for those with no exposure to stressful life events.
By comparison, severe life events did not increase likelihood of new-onset sleep disturbance among men not prone to anxiety.
For women in the study, liability to anxiety in combination with stressful events in the prior six months raised the risk of new-onset sleep problems 1.54- to 2.38-fold (95% CI 1.07 to 4.13).
Although acute sleep problems may increase risk of chronic sleep disturbances, liability to anxiety was not linked to sleep disturbance and life events long term (P>0.10).
"This heightened vulnerability was evident, however, only zero to six months after the event," Dr. Vahtera and colleagues wrote.
Dr. Vahtera and a co-author reported support from the Academy of Finland.Primary source: SLEEPSource reference: Vahtera J, et al "Liability to Anxiety and Severe Life Events as Predictors of New-Onset Sleep Disturbances" SLEEP 2007; 30: 1449-1458.