Alzheimer’s Disease and CAPD: George Gates’ Contributions

by Giau N. Le, B.S. and Frank E. Musiek, Ph.D., The University of Arizona

Introduction

Alzheimer’s disease (AD) is a disorder of the neurodegenerative disease that primarily effects the elderly population. There are approximately 5.2 million people living with AD in the United States. Of that population, 5 million of those individuals are over the age of 65 years (Fargo, 2014). The Center for Disease Control has indicated that the elderly (65 years and older) population should continue to show significant population growth, as 20% of the population in the United States will be elderly by the year 2050 (CDC, 2014). Additionally, by the year 2020, one new case of AD is expected to develop every 33 seconds; therefore, better management options and early detection tools should be a priority (Fargo, 2014).

Symptoms of AD include memory impairments, language, and learning difficulties, as well as poor emotional management. Because Alzheimer’s also impair motor function, such as swallowing, most patients with AD will die from aspiration (i.e., pneumonia) (Kalia, 2003). At the microscopic level, individuals with AD will have fewer nerve cells and synapses, compared to the normal population (Reece et al., 2012). Plaques and tangles are thought to be primary causes in the development of AD. Plaques, which are found in the brain, create abnormal clusters of protein (i.e., beta-amyloid) fragments. The chemically “sticky“ beta-amyloid proteins are generally found in the fatty membranes that surround nerve cells. Plaques are known to cause cell death in addition to impairments in nerve cell conductivity, which cause information transferred between nerve cells to be distorted or completely lost (Hardy & Selkoe, 2002). Patients with AD will also have tangles in the brain. Tangles are twisted stands of protein. Normally, proteins are arranged in an orderly and parallel manner. They are vital in the process of cell transport; however, if tangled, the ability to transfer nutrients and information down the axon will be impaired (Reece et al., 2012). A protein commonly referred to as ‘tau” is charged with the task of ensuring that the tracks stay straight and parallel. Dysfunction of the tau proteins causes them to collapse into strands (i.e., tangles) (Reece et al., 2012). Although there is not a complete consensus among scientists regarding the causes of AD, many believe it is due to plaques and tangles (Hardy & Selkoe, 2002). It should be noted that there are individuals with plaques and tangles who do not develop AD; therefore, additional research in this area is warranted.

AD is an extremely difficult diagnosis for the individual and their family to live with. While there is currently no cure for AD, early detection and intervention may help the patient and their families delay the devastating symptoms. Research regarding the efficiency of central auditory processing tests in detecting early signs of AD has been demonstrated. Because the temporal lobe is one of the first structures to be effected by this disease, a central auditory processing test can provide early and valuable insight pertaining to the potential risk for AD.

History

A pioneer in this area is Dr. George Gates, Emeritus Professor of the University of Washington. Dr. Gates is an otolaryngologist as well as a neuro-otologist. He was the former director of the Virginia Bloedel Hearing Research Center at the University of Washington (Otonexus.com). Dr. Gates’ work regarding early detection of AD began when he was appointed as a lead researcher, in the category of hearing, for the Framingham Heart Study. Initially, Dr. Gates and his colleagues examined hearing loss using audiologic test that evaluated the peripheral system; however, Dr. Gates had the remarkable foresight to examine the auditory system, beyond the periphery. He began to use behavioral central auditory processing tests to assess the health of the auditory system beyond the cochlea. Subsequently, Dr. Gates’ research revealed the prognostic value of central auditory tests in detecting AD.

Behavioral Central Auditory Processing Tests and Alzheimer’s Disease

In 2002, Dr. Gates and colleagues published assessed, using various audiologic test, seven hundred and forty dementia free older adults from the Framingham Heart Study for probable AD. The adults had symmetric hearing thresholds (loss no greater than 35 dB HL) and “normal” word recognition ability (score of > 80% on W-22 list). Researchers used the Synthetic Sentence Identification test with ipsilateral competing messages (SSI-ICM) in at least one ear to assess the subjects. The SSI-ICM protocol involves the presentation of a synthetic (i.e., nonsense) sentence in one ear at a comfortable listening level, while a meaningful competing message is delivered to the same ear (Jerger & Speaks, 1965). Dr. Gates and others attempted to determine the correlation between speech processing deficits (i.e., score of 50% or less on the SSI) and the probability of developing AD. Subjects with normal speech recognition ability but abnormal SSI-ICM test scores were labeled “Caspd.” The results of this study showed that there were a total of fifteen subjects with the Capsd label. Furthermore, 7/15 Caspd subjects were found to have probable AD. They were mostly male and generally older (compared to the participants without dementia). The sensitivity of the SSI-ICM test in detecting probable AD was found to be approximately 47%, while the specificity was approximately 17.5% (Gates et al., 2002).

By employing the Cox proportional hazard regression, researchers also found that a central auditory speech-processing deficit along with other risk variables had a positive predictive value for subsequent development of AD (please see figure below for details). The relative risk of developing AD for the Caspd group, relative to the normal group, was derived from the risk ratio. While age (during the time of testing) had a risk ratio of 10.8, factors such as age, gender, presence of apo E4 (aploipoprotein allele E4), low educational attainment (high school degree), and poor pure tone average thresholds, combined, had the greatest risk ratio of 23.3 (95% confidence interval=6.6-82.7). These results indicate that a central auditory deficit in conjunction with other risk factors may herald AD; therefore, central auditory processing tests are invaluable tools for the early detection of AD (Gates et al., 2002).

Additional research by Dr. Gates and colleagues (2008) used behavioral central auditory processing and electrophysiological tests to assess auditory function in a cohort of 313 older adults in a dementia surveillance program. The primary objective of this study was to determine whether central auditory testing might be suitable for identifying individuals at risk for dementia, as central auditory function is usually compromised in people with a diagnosis of AD. The cohort consisted of three groups, the controls without memory loss (n=232), targets with mild dementia, no memory loss (n=64), and targets with a dementia diagnosis (n=17). Behavioral measures included the synthetic sentence identification with ipsilateral competing message (SSI-ICM) as outlined by Jerger et al., 1994, the dichotic sentence identification (DSI) test (Fifer et al., 1983), the dichotic digit test (DDT) (Musiek et al., 1991), and the pitch pattern sequence (PPS) test (Musiek, Pinheiro, &Wilson, 1980; Strouse, Hall, & Burger, 1995; Musiek & Pinheiro, 1987). Researchers considered a score less than 80% on the CAPD tests abnormal. Electrophysiologic tests performed across all subjects included the auditory brainstem response (ABR), middle latency response (MLR), and the late latency response (LLRR).

Using the previously mentioned behavioral CAPD tests, Gates and colleagues (2008), demonstrated that even mild dementia affected central auditory function (Gates et al., 2008). The DSI test (in free report mode) had the best sensitivity and specificity results, relative to the other CAPD tests. The sensitivity and specificity for the DSI test was 83.3% and 58.6 test. In contrast, the PPS test was least sensitive to detecting the presence of a central auditory impairment (Gates et al., 2008). The area under the curve (AUC) was greatest (0.86), when all of the behavioral tests were administered to the test subject (Gates et al., 2008). Furthermore, the DSI test (using free recall), as a stand-alone test, had the greatest area under the curve (0.83). In contrast, the PPT had the least AUC (0.71). The DSI test using free recall may have been the most sensitive and specific test in detecting central auditory processing deficits and subsequent AD because this test is demanding on short-term memory, which is usually impaired in patients with AD. The PPS test may have had the least AUC because subjects were able to use both pitch and timing cues to produce the correct response. Additionally, the DSI test (free recall) may have been more demanding linguistically and memory-wise, as subjects were required to retain entire sentences, in both ears, for later recall. Furthermore, the PPS test, which is sensitive to lesions at the corpus callosum, may not be the best tool to assess compromised auditory function in patients with AD. Finally, electrophysiologic test results did not differ across all three groups in the study. These results, once again, show the prognostic value of behavioral central auditory tests in predicting central auditory impairment in older adults at risk for AD (Gates et al., 2008).

Clinical Implications

Gates (2012), discussed the barriers associated with implementing central auditory processing test. The lack of knowledge regarding which test to use was revealed as a deterrent. Test materials and reimbursements have also been reported as problems regarding clinical implementation. Finally, time constraints have been described as a major barrier pertaining to routine implementation of CAPD test in clinical practice. While these concerns are valid, many central auditory processing test batteries can be implemented in less than an hour. The DDT can be performed in approximately four minutes. In contrast, the SSI-ICM takes approximately twenty minutes or less in most patients, which includes the instruction and training portion of the test (Gates, 2012). Given that central auditory degeneration is highly prevalent in the elderly population, including those with AD, it is imperative that CAPD testing is performed when central processing deficits are suspected (e.g., patient complains of speech perception deficits in the presence of noise). While the barriers above may be hard to overcome, implementation of central auditory test results may have a direct impact on rehabilitation; therefore, assessment of the entire auditory system is warranted (Gates, 2012).

There are many significant benefits to using central auditory processing tests in clinical practice, especially in elderly patients at risk for AD. Central processing tests are non-invasive and cost-effective compared to PET and CT scans. Additionally, detection of plaques and tangles do not always mean that AD is present (especially in the early stages); therefore, looking at the individual’s functional speech processing abilities may be the best approach for this population. Behavioral testing can be used to explain communication difficulties and breakdowns, giving the patient and their families a better understanding of why the breakdowns occur. This is important and potentially therapeutic for the individual and their family. Additionally, clinicians can use central auditory tests to garner insight regarding the communication difficulties experienced by the individual. This is critical for intervention and rehabilitation planning, as behavioral testing can show functional auditory impairments (i.e., impaired temporal processing). Behavioral testing can also be used to monitor the efficacy of rehabilitation and intervention, which is important for the cost-benefit analysis of treatment.

Like many other diseases, AD management will require a team of professionals and physicians. The Audiologist’s main goals are to measure the integrity of the hearing system and to determine ways to improve or maintain communication for the patient. Amplification may be an option for patients with dementia, especially if there is peripheral hearing loss. Getting the input to the brain is a first step for these patients. Caution should be taken when fitting hearing aids to this special population, as binaural interference may occur; therefore, consideration of a monaural fitting may be advantageous (Jerger et al., 1993; Chermak & Musiek, 2007). Difficulties understanding speech in noise is often a complaint that patients have. An FM (frequency modulation) system may be another tool that can be used to manage central processing difficulties (Chermak & Musiek, 2007). FM systems increase the signal to noise ratio in order to enhance the signal for the patient, which is helpful in the presence of background noise.

Auditory training therapy should also be considered for this population. One example is the Learning and Communication Enhancement (LACE) program, which utilizes auditory-visual speech perception training techniques (Seetow & Sabes, 2006). Adults with peripheral hearing loss and central processing impairments can use LACE as part of their rehabilitation plan (Chermak & Musiek, 2007). While commercial programs can be beneficial, it is important to always address the individual’s deficits during auditory training therapy (Musiek & Chermak, 1990). However, caution should be practiced when prescribing auditory training programs to patients, as a strong evidence base for the program is needed before encouraging the patient to invest their money and time.

Strategies to repair communication breakdowns can be used to alleviate communication difficulties. Obtaining the listeners attention prior to speaking, using simple sentences and asking closed ended questions (i.e., yes or no) when speaking with patients with AD has been shown to helpful (Small et al. 2003). An additional strategy that may repair communication breakdowns includes uses of request for clarification, which has shown to facilitate understanding between conversational partners (Tye-Murray et al., 1990). Repair strategies that elicit rephrasing by the communication partner are more likely to mend communication breakdowns (Gagne & Wyllie, 1989). Using clear speech has also shown to be conducive to repairing communication breakdowns (Caissie et al., 2005). In contrast, verbatim repetition after a breakdown has occurred, as well as slows speech has been shown to be unhelpful (Small et al., 2003). Specific training in the use of the aforementioned repair strategies has been shown to be effective (Tye-Murray, 1991; Caissie et al., 2005). Finally, reducing background noise and providing visual cues (i.e., visualization of the speakers lips) for the hearing impaired listener may also facilitate successful communication (Keith, 1999; Erber 1975).

Finally, intervention can also include modifying the individual’s behavior to make it more conducive to their goals and needs (i.e., autonomy). Short-term memory is usually impaired in patients with AD; however, long-term memory is relatively intact. Asking the patient to practice everyday things (i.e., insertion of hearing aids) in order to develop motor memory could be helpful, as constant practice conditions in patients with AD has been shown to facilitate motor memory (Dick et al., 1996).

Summary

The research mentioned above show the importance of assessing the auditory system beyond the periphery, as lesions may be beyond the cochlea or auditory nerve (Gates et al., 2008). This point is especially pertinent in patients with AD, as peripheral hearing tests and routine evoked potentials, such as the auditory brainstem response (ABR), do not provide valuable insight regarding central auditory function (Jerger & Hall, 1980). With age, both the peripheral and central auditory systems will show degeneration. While routine clinical test are able to assess the peripheral degeneration, the damage to the central auditory system will remain undetected. Pioneers, such as Dr. Gates, had the foresight to examine central auditory processing test in patients with AD. His research demonstrated the clinical utility of behavioral auditory processing tests and the early detection of dementia. The results of the previously mentioned studies show that pathologies of the brain cannot be detected using routine audiological tests (e.g., pure tone audiogram, otoacoustic emissions, and word recognition scores); therefore, a more holistic approach in how we assess the auditory system needs to be implemented, especially by the Audiologist (Gates et al., 2008). Elderly patients with AD are complex patients that are prone to communication and speech perception difficulties. Aside from the AD, this population is susceptible to the effects of aging. Generally, older adults show reduction in brain plasticity, less neural synchrony (time-locking), and central inhibition (Chermak & Musiek, 2007). The elderly population is more prone to peripheral hearing loss (presbycusis) and speech perception difficulties. Peripheral hearing loss is the third most common chronic health condition impacting the elderly population (Yorkston, Bourgeois, & Baylor, 2011). Additional factors such as age and peripheral hearing loss must be considered when testing this population. Behavioral central auditory processing tests can be used to fully understand the communication impairment and to guide treatment.

Giau Ngoc Le is a fourth year Doctor of Audiology student at the University of Arizona. She graduated magna cum laude from the University of Arizona with a BS in Speech, Language, and Hearing Sciences. Giau was the President of the University of Arizona Student Academy of Audiology for three years and has been involved in several research projects, while maintaining various jobs. She has worked as a Teaching Assistant for the University of Arizona, a Medical Scribe for Banner Health Medical Center, and as an Audiology Technician for the Arizona School for the Deaf and Blind. Giau is interested in working with adults suspected of speech-processing deficits due to various traumas and diseases (e.g., Alzheimer’s disease and traumatic brain injury). She hopes to share her knowledge in a university setting as a faculty member. Giau is also determined to train hearing healthcare personnel in Thailand and Southeast Asia, to administer hearing services to their local communities. In July 2015, she will begin her externship at the Mayo Clinic in Scottsdale, Arizona.

References

Caissie, R., Campbell, M, N., Frenette, W, L., Scott, L., Howell, I., Roy, A. (2005). Clear for adults with a hearing loss: does intervention with a communication partner make a difference speech. Journal of the American Academy of Audiology, 16, 157-171.

Chermak, G, D., & Musiek, F, E. (2007). Handbook of (central) auditory processing disorder Volume II. (1^st ed.) Plural Publishing Inc: San Diego, CA.

Dick, M, B., Shankle, R, W., Beth, R, E., Dick-Muehlke, C., Cotman, C, W., Kean, M. (1996). Acquisition and long-term retention of a gross motor skill in Alzheimer’s disease patients under constant and varied practice conditions. Journal of Gerontology, 51B, P103-P111.

Erber, N, P. (1975). Auditory-visual perception of speech. Journal of Speech and Hearing Disorder, 40, 481-492.

Fargo, K. (2014). 2014 Alzheimer’s disease facts and figures. Alzheimer’s Dementia, 10(2), 47- 92.

Gagne, J., & Wyllie, K, M. (1989). Relative effectiveness of three repair strategies on the visual- identification of misperceived words. Ear and Hearing, 10, 368-374.

Gates, G, A. (2012). Presbycusis: a brain disorder? “The ears listen, the brain hears.” Seminars in  Hearing, 33(3), 225-229.

Gates, G, A., Beiser, A., Rees, T, S., D’Agostino R, B., Wolf, P, A. (2002). Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer’s disease. Journal of American Geriatrics Society, 50(3), 482-488.

Gates, G, A., Anderson, M, L., Feeney, M, P., McCurry, S, M., Larson, E, B.( 2008). Central auditory dysfunction in older people with memory impairment or alzheimer’s dementia. Archive of Otolaryngology Head and Neck Surgery, 134(7). 771-777.

Gates, G, A., Feeney, M, P., Mills, D. (2008). Cross-sectional age-changes of hearing in the elderly. Ear and Hearing, 29(6), 865-874.

Hardy, J., & Selkoe, D, J. (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 297, 353-356.

Jerger, J., & Hall, J. (1980). Effects of age and sex on auditory brainstem response. Archives of  Otolaryngology-Head and Neck Surgery, 106(7), 387-391.

Jerger, J., Silman S., Lew, H., Chmiel, R. (1993). Converging evidence from behavioral and electrophysiologic measures. Journal of the American Academy of Audiology, 4, 122-131.

Kaila, M. (2003). Dysphagia and aspiration pneumonia in patients with Alzheimer’s disease. Metabolism, 52 (10S2), 36-38.

Keith, R, W. (1999). Clinical issues in central auditory processing disorders. Language, Speech, and Hearing Services in Schools, 30, 339-344.

Musiek, F, E. & Chermak, G, D. (2007). Handbook of (central) auditory processing disorder Volume I. (1^st ed.) Plural Publishing Inc: San Diego, CA.

Musiek, E, F., & Chermak, G, D. (1994). Three commonly asked questions about central auditory processing disorders: management. American Journal of Audiology, 4(1), 15-18.

Musiek, E, F., & Pinheiro, M, L. (1987). Frequency patterns in cochlear, brainstem, and cerebral lesions. Audiology, 26, 79-88.

Musiek, E, F., Pinheiro, M, L., Wilson, D, H. (1980). Auditory pattern perception in ‘split brain’ patients. Archives of Otolaryngology-Head and Neck Surgery, 106, 610-612.

OtoNexus. Medical technologies. Retrieved from http://www.otonexus.com/leadership.html

Reece, J., Urry, L, A., Meyers, N., Cain, M, L., Wasserman, S, A., Minorsky, P, V., Jackson, R, B., Cooke, B, N. (2013). Campbell biology. (10^th ed). Pearson Publishing Inc: New York, NY.

Seetow, R, W., Sabes, J, B. (2006). The ned for development of an adaptive listening and communication enhancement (LACE) program. Journal of the American Academy of Audiology, 17, 538-558.

Small, J., Gutman, G., Makela, S., Hillhouse, B. (2003). Strategies used by caregivers of persons with Alzheimer’s disease. Journal of Speech, Language, and Hearing Research, 46, 353-367.

Strouse, A, L., Hall, J, W., Burger, M, C. (1995). Central auditory processing in Alzheimer’s disease. Ear and Hearing, 16, 230-238.

Tye-Murray, N, (1991). Repair strategy usage by hearing-impaired adults and changes following communication therapy. Journal of Speech, Language, and Hearing Research, 34, 921-928.

Tye-Murray, M, N., Purdy, S, C., Woodworth, G, G., Tyler, R, S. (1990). Effects of repair strategies on visual identification of sentences. Journal of Speech and Hearing Disorder, 55(4), 621-627.

Yorkston, K, M., Bourgeois, M, S., Baylor, C, R. (2011). Communication and aging. Physical Medicine & Rehabilitation Clinics of North America, 21(2), 309-319