Mutation in Gene Connected to Fatigue in Shift Workers Could Also Increase Risk of Alzheimer’s

Research by the same team points to the possible connection between shift work intolerance and later development of Alzheimer’s

Shift workers often experience disruptions to their sleep patterns and the circadian rhythm. Daytime fatigue and sleep disorders tend to be common side effects. These are also risk factors for developing Alzheimer’s disease. Now that both have been connected to the same variation in MTNR1A, the results appear to connect the genetic predisposition to “shift work intolerance” and the development of Alzheimer’s. It should be noted that shift work intolerance varies between individuals.

The new study focused mainly on the connection between the variation of the MTNR1A gene and the development of Alzheimer’s. The research team, lead by Tiina Paunio, University of Helsinki and National Institute for Health and Welfare, Finland, showed that the MTNR1A variation is also linked to brain lesions visible in post-mortem brain tissues. Additionally, the beta-amyloid protein feature of Alzheimer’s disease began to accumulate when MTNR1A expression was reduced in the cell culture.

The previous study showed a connection between lower levels of MTNR1A expression in the brain and shift work intolerance. Therefore, the old conclusions seem to be compatible with the new findings.

“The finding of a common risk gene for both job-related exhaustion in shift workers and Alzheimer’s disease doesn’t directly mean that shift work would predispose to Alzheimer’s disease,” says Lic. Med Sonja Sulkava from the National Institute for Health and Welfare, Finland. “However, the combination of genetic predisposition and a lifestyle that disrupts the circadian rhythm can increase the risk of Alzheimer’s disease. Another possible interpretation is that the brain dysfunctions related to Alzheimer’s disease impair the tolerance to shift work decades before the onset of the clinical disease.”

In other words, shift work does not necessarily contribute to a risk of Alzheimer’s. However, having both the gene mutation and a lifestyle that increases sleep disruption could increase the possibility of Alzheimer’s disease.

Study Participants

The research cohorts were comprised of four groups of participants.

The first and primary group consisted of people over the age of 85 living in Vantaa, Finland starting in 1991. Survivors were re-examined for dementia status in 1994, 1996, 1999 and 2001. Participants who had dementia were differentiated between those who had “pure” Alzheimer’s and those with mixed cases of Alzheimer’s and vascular dementia. Neuropathological autopsies were completed in 304 of these participants, the only group the researchers autopsied.

The second group included participants aged 75 and older living in Kuopio, Finland beginning in 1998. Follow-up exams were completed five years later. Information was gathered via clinical exams and interviews with doctors, caregivers and relatives. The participants with dementia in this group were also categorized as having either Alzheimer-type dementia or vascular dementia.

Groups three and four were part of a case-control study whose participants ranged from middle age to elderly. Group three had only people with pure Alzheimer-type dementia, and the fourth was the control group. All participants in these two groups were from the same communities of Eastern Finland.

The association between the variant in the melatonin receptor gene and Alzheimer’s was only seen in the two elderly cohorts and not the younger case-control groups.

Final Thoughts

The results from the two studies seem to suggest that a career in shift work could be one contributing factor to Alzheimer’s disease later in life. The link between disruptions in sleep patterns and circadian rhythm and the development of Alzheimer’s has been established. Sleep disruptions are common among shift workers. So in that sense, it would seem there could be a connection between shift work and the onset of Alzheimer’s.

And now, the two studies conducted by the same research team suggests the same variation of the MTNR1A gene could lead to both shift work intolerance and the development of Alzheimer’s later in life.

The connection is certainly interesting, but not conclusive by any means.

“Even though our results demonstrate a new molecule-level connection between the tolerance to shift work and incipient Alzheimer’s disease,” says professor Paunio, “the now discovered genetic variation has a minimal effect on the individual level and it can’t be used to risk assessment or prediction.”

Clearly further research needs to be conducted to make any sort of definitive statements regarding shift work, gene variations and the development of Alzheimer’s.