21 Feb 2011

If you haven’t yet checked out this month’s Archives of Neurology, lend us your ears—hearing-impaired seniors could face a higher risk of developing dementia. That’s the conclusion of a prospective study by Frank Lin, Johns Hopkins School of Medicine, Baltimore, Maryland, and colleagues, who followed 639 dementia-free seniors for about 12 years. The mechanisms underlying the association between hearing loss and dementia remain unclear, as each trait is strongly linked to age. Nevertheless, the authors are gearing up for a pilot study of whether hearing aids can improve cognition over a few years’ timeframe.

The “original inkling” for this study was a case-control analysis published 22 years ago (Uhlmann et al., 1989), Lin told ARF. In that study, scientists found more hearing loss in a group of 100 people with Alzheimer’s-type dementia than in 100 non-demented controls matched for age, gender, and education. Other research has also suggested that dementia may be more common in hearing-impaired individuals (see Ives et al., 1995), and smaller prospective studies have linked hearing loss to faster cognitive decline in people with diagnosed dementia (Peters et al., 1988; Uhlmann et al., 1986). In the current paper, Lin and colleagues report a longitudinal prospective study to determine whether auditory status could predict future development of dementia.

The Johns Hopkins team followed dementia-free participants aged 36 to 90 years and recruited between 1990 and 1994 for the Baltimore Longitudinal Study of Aging. This is an ongoing study of local volunteers the National Institute on Aging launched in 1958. The researchers categorized the participants into one of four groups, comprising people with normal hearing, or mild, moderate, or severe hearing impairment. Of the 639 participants, 455 tested “normal” (i.e., able to hear above 25 decibels), 125 were judged as “mild” (i.e., hears a minimum of 25-40 decibels and finds communication difficult in places with background noise), 53 as “moderate” (hears a minimum of 40-70 decibels and communicates poorly, even in quieter environments), and six as “severe” (only hears >70 decibels; can only communicate if face to face). Typical conversation occurs at about 60 decibels; a jet engine registers close to 120. Those with greater hearing loss tended to be older men with high blood pressure; however, people’s cognitive ability did not differ among hearing categories at baseline.

Study volunteers underwent cognitive testing every two years, until 1997. At that point, testing shifted to every year for those older than 80 years, and every four years for people under 60. During the study, 58 participants—including nearly a third of those in the moderate and severe hearing impaired groups—developed dementia. With adjustments for gender, age, race, education, diabetes, smoking, and blood pressure, the study “clearly shows that greater hearing loss is associated with an increased risk of developing dementia over time,” Lin said.

Another prospective study that looked for a relationship between hearing acuity and cognitive test scores in healthy elderly found no such link (Gennis et al., 1991), and some scientists had concerns about the current analysis. Lewis Kuller of the University of Pittsburgh, Pennsylvania, noted that it is hard to control for the large age spread between normal participants (mean age 59.9 years) and those with moderate or severe hearing impairment (mean age over 77 years). Claudia Kawas of the University of California, Irvine, pointed out that the analysis included very few people with severe hearing loss. She speculated, in an e-mail to ARF, whether this might be because such individuals are hard to test reliably. Lin contends this was not a problem in the current study. “Even for people with severe hearing loss,” he said, “as long as you’re one-on-one, face-to-face with them in a quiet room, they’ll understand everything you’re saying.”

Why would hearing loss be linked to incident dementia? “That’s the hundred billion dollar question,” Lin said. He described three possibilities, which may not be mutually exclusive. According to one theory, hearing loss leads to social isolation or loneliness, which has been associated with increased dementia risk (Wilson et al., 2007). The second possibility is that hearing loss shifts energy toward decoding auditory signals, leaving the brain more vulnerable to pathological changes that lead to dementia. Lastly, “maybe there’s a common pathway leading to both hearing loss and dementia,” Lin suggested.

Deborah Blacker of Massachusetts General Hospital, Boston, offered another possibility. It is “possible that sensory loss could simply contribute to the functional decline necessary to cross the threshold for dementia,” she wrote in an e-mail to ARF. She added that “...people with hearing loss would be expected to have more functional impairment for a given level of cognitive loss or underlying brain pathology.”

Lin hopes other groups will perform studies to confirm the present findings. The Baltimore cohort contains predominantly white men with high socioeconomic status, and hence, may not reflect trends in the general population.

In the meantime, Lin and colleagues have secured funding for a two-year exploratory study to test whether hearing aids can improve cognition in Johns Hopkins patients who are about to get hearing aids or cochlear implants. The team hopes to begin recruiting for the study, dubbed SMART (Studying Multiple Outcomes After Aural Rehabilitative Treatment), this summer. Lin and colleagues are also looking for associations between hearing loss and changes in brain size or morphology, as measured by magnetic resonance imaging. “Realistically, (hearing aids) are not going to cure dementia. At best, they may delay its onset for maybe a year or two. But even that would have a profound impact on society,” Lin said. He cited a recent report suggesting that pushing back memory loss symptoms by just one year could drop the global prevalence of dementia more than 10 percent by 2050 (Brookmeyer et al., 2007).—Esther Landhuis

Comments

1. • Deborah Blacker
     
   • Posted: 21 Feb 2011
   • Paper: Hearing loss and incident dementia.

   This paper confirms in some detail the old clinical pearl that sensory loss is associated with dementia, and shows a dose response as well. In addition to the potential mechanisms thoughtfully discussed here, it's also possible that sensory loss could simply contribute to the functional decline necessary to cross the threshold for dementia. It's that much harder to manage a wide variety of life tasks when a critical information source is lost, so people with hearing loss would be expected to have more functional impairment for a given level of cognitive loss or underlying brain pathology.

   View all comments by Deborah Blacker
2. • M. Flint Beal
     Weill Cornell Medical College
   • Posted: 02 Mar 2011

   One other possibility for linking hearing loss to dementia is that both may reflect mitochondrial impairment. Hearing loss occurs with mitochondrial disorders such as MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Age-related hearing loss is prevented by caloric restriction, and this is mediated by Sirt3 which regulates isocitrate dehydrogenase, leading to increased NADPH and reduced glutathione in mitochondria (Someya et al., 2010). Sirt3 also plays a role in activation of MnSOD in response to caloric restriction.

   References:

   Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010 Nov 24;143(5):802-12. PubMed.

   View all comments by M. Flint Beal

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References

Paper Citations

1. Uhlmann RF, Larson EB, Rees TS, Koepsell TD, Duckert LG. Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. JAMA. 1989 Apr 7;261(13):1916-9. PubMed.
2. Ives DG, Bonino P, Traven ND, Kuller LH. Characteristics and comorbidities of rural older adults with hearing impairment. J Am Geriatr Soc. 1995 Jul;43(7):803-6. PubMed.
3. Peters CA, Potter JF, Scholer SG. Hearing impairment as a predictor of cognitive decline in dementia. J Am Geriatr Soc. 1988 Nov;36(11):981-6. PubMed.
4. Uhlmann RF, Larson EB, Koepsell TD. Hearing impairment and cognitive decline in senile dementia of the Alzheimer's type. J Am Geriatr Soc. 1986 Mar;34(3):207-10. PubMed.
5. Gennis V, Garry PJ, Haaland KY, Yeo RA, Goodwin JS. Hearing and cognition in the elderly. New findings and a review of the literature. Arch Intern Med. 1991 Nov;151(11):2259-64. PubMed.
6. Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, Tang Y, Bennett DA. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007 Feb;64(2):234-40. PubMed.
7. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007 Jul;3(3):186-91. PubMed.

Further Reading

Papers

1. Uhlmann RF, Larson EB, Rees TS, Koepsell TD, Duckert LG. Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. JAMA. 1989 Apr 7;261(13):1916-9. PubMed.
2. Ives DG, Bonino P, Traven ND, Kuller LH. Characteristics and comorbidities of rural older adults with hearing impairment. J Am Geriatr Soc. 1995 Jul;43(7):803-6. PubMed.
3. Peters CA, Potter JF, Scholer SG. Hearing impairment as a predictor of cognitive decline in dementia. J Am Geriatr Soc. 1988 Nov;36(11):981-6. PubMed.
4. Uhlmann RF, Larson EB, Koepsell TD. Hearing impairment and cognitive decline in senile dementia of the Alzheimer's type. J Am Geriatr Soc. 1986 Mar;34(3):207-10. PubMed.
5. Gennis V, Garry PJ, Haaland KY, Yeo RA, Goodwin JS. Hearing and cognition in the elderly. New findings and a review of the literature. Arch Intern Med. 1991 Nov;151(11):2259-64. PubMed.
6. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007 Jul;3(3):186-91. PubMed.
7. Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, Tang Y, Bennett DA. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007 Feb;64(2):234-40. PubMed.