This study by Yaffe, et al. provides a new avenue of investigation into a potentially modifiable risk factor for developing mild cognitive impairment (MCI) or dementia. The study is the first to show a temporal relationship where sleep-disordered breathing with hypoxia seems to occur before the onset of MCI or dementia. However, further work will be needed to confirm the temporal, cause-effect relationship prior to suggesting clinical interventions for sleep-disordered breathing with hypoxia as a prevention for dementia. The pathology changes in the brain (amyloid plaques, tangles, infarcts, and Lewy bodies) seem to build up for decades during the cognitively asymptomatic phase of dementia. Therefore, the study findings may be explained by brain pathology affecting the central brain pathways for regulating respiration in sleep earlier than affecting pathways associated with cognition. Also, it would be helpful to determine what brain pathology is associated with the dementia older women with sleep-disordered breathing developed as compared to older women without sleep-disordered...  Read more

This study by Yaffe, et al. provides a new avenue of investigation into a potentially modifiable risk factor for developing mild cognitive impairment (MCI) or dementia. The study is the first to show a temporal relationship where sleep-disordered breathing with hypoxia seems to occur before the onset of MCI or dementia. However, further work will be needed to confirm the temporal, cause-effect relationship prior to suggesting clinical interventions for sleep-disordered breathing with hypoxia as a prevention for dementia. The pathology changes in the brain (amyloid plaques, tangles, infarcts, and Lewy bodies) seem to build up for decades during the cognitively asymptomatic phase of dementia. Therefore, the study findings may be explained by brain pathology affecting the central brain pathways for regulating respiration in sleep earlier than affecting pathways associated with cognition. Also, it would be helpful to determine what brain pathology is associated with the dementia older women with sleep-disordered breathing developed as compared to older women without sleep-disordered breathing with hypoxia. It could be that sleep-disordered breathing is more likely to be linked to infarcts rather that AD pathology. Infarcts have been shown to accelerate the manifestation of dementia symptoms. Again, this paper is an important contribution to our understanding of dementia and opens up novel avenues for further exploration.

View all comments by Raj C. Shah

This is an important and provocative observational study. The notion that sleep apnea could be associated with cognitive impairment has been documented in the scientific literature for over 25 years; what this study does, somewhat uniquely, is demonstrate that in an elderly community population, sleep apnea may lead unambiguously to progressive decline in cognition over time. However, the implications of the study for treatment remain uncertain (as would be the case for any observational study).

Unresolved issues for treatment would be: 1) At what point to initiate treatment? 2) How long would it take to see a response? 3) What kind of treatment would one undertake? 4) (related to #1 and #2) What would constitute a response?

To place this all in context, there can be no doubt that treating cognitively impaired, elderly patients' hypertension, cardiac insufficiency, or diabetes would help their overall physical function and might improve some elements of cognition as well, but to infer that acute treatment of such conditions would cure dementia would be misleading. On the...  Read more

This is an important and provocative observational study. The notion that sleep apnea could be associated with cognitive impairment has been documented in the scientific literature for over 25 years; what this study does, somewhat uniquely, is demonstrate that in an elderly community population, sleep apnea may lead unambiguously to progressive decline in cognition over time. However, the implications of the study for treatment remain uncertain (as would be the case for any observational study).

Unresolved issues for treatment would be: 1) At what point to initiate treatment? 2) How long would it take to see a response? 3) What kind of treatment would one undertake? 4) (related to #1 and #2) What would constitute a response?

To place this all in context, there can be no doubt that treating cognitively impaired, elderly patients' hypertension, cardiac insufficiency, or diabetes would help their overall physical function and might improve some elements of cognition as well, but to infer that acute treatment of such conditions would cure dementia would be misleading. On the other hand, by attending to health issues such as these (and this would include sleep apnea) over the long term (i.e., from middle age on through old age), one is likely to reduce that burden of medical disease on higher brain function and could very well prevent (or at least forestall) the onset for impaired cognition in late life.

Note: This comment was invited by the Alzheimer Research Forum.

View all comments by Donald L. Bliwise

This report should be supported by the pathogenic confirmation of Alzheimer’s disease, but it is still a very attractive observation for the Alzheimer’s field. Currently, it is popular to clarify the pathogenic mechanisms that induce MCI or early Alzheimer’s dementia, and this paper has opened a new window on MCI. It is well known that hypoxia generates oxygen radicals, which have harmful effects on neuronal function. Hypoxia has recently been linked to MCI and dementia.

We recently found that homocysteic acid (HA) is a possible risk factor for AD, and that it may be linked to hypoxia (1).

We observed that cystathionine β-synthase (CBS) can produce HA via homocysteine and oxygen radicals, and that HA might affect the hippocampus to cause memory impairment in transgenic mice (2). That the same might happen in humans may be tested by the detection of blood HA in MCI patients. We are working on this now.

Finally, older women who suffer from sleep hypoxia may benefit from antioxidants, which suppress oxygen radicals.

References:
1. Hasegawa, T. Ichiba, M. and Tabira, T: ICAD 2011, Paris, p3-153.

2. Hasegawa T, Mikoda N, Kitazawa M, LaFerla FM (2010) Treatment of Alzheimer’s Disease with Anti-Homocysteic Acid Antibody in 3xTg-AD Male Mice. PLoS ONE 5(1): e8593. Abstract

View all comments by Tohru Hasegawa