Cognitive Impairment and Hearing Loss Discussion Replies

Reply 1:
Hearing loss as a risk factor for cognitive impairment and loss of synapses in the hippocampus
1.
Research on the cause of diseases resulting in cognitive disabilities, such as Alzheimer’s,
has long been an area of interest. Prior to this study, only epidemiologic evidence suggested a
link between hearing loss and cognitive dysfunction. This study aimed to use animal models to
find the pathophysiology between the two.
This study was conducted using mice and was made up of two different stages. The first
was to determine how long after the loss of the ability to hear cognitive abilities start to decline.
The second stage was to see what changes, in regard to cognitive ability, occurred and any
difference in synaptic protein levels. Since previous studies showed that hearing loss on its own
did not induce any cognitive changes, the mice were administered amyloid-b in order to make
the brain more vulnerable to risk factors (Chang et al., 2019).
To determine a timeline in the first stage, the mice were split into two groups, the first
half of which were normal hearing subthreshold Ab group that underwent a sham surgery. The
second group was the deaf subthreshold Ab group that underwent bilateral cochlear ablation
surgery. Both groups also had an infusion of subthreshold Ab. Both groups of mice performed
the Y-maze test every 2 weeks in order to determine the timeline in which hearing loss induced a
significant effect of cognitive impairment. The results of this showed that the deaf-SA group had
much lower Y-maze scores than the NH-SA group (Chang et al., 2019).
In the second stage of testing, the mice were split into 4 groups: normal hearing non-Ab
(sham surgery only), normal hearing subthreshold Ab (sham surgery and infusion of
subthreshold Ab), deaf non- Ab (bilateral cochlear ablation only), deaf subthreshold Ab (bilateral
cochlear ablation and infusion of subthreshold Ab). Following surgery, all mice participated in a
series of tests that analyzed cognitive ability. The results from these tests showed that the deafSA group had significantly lower scores than the 3 other groups. After completion of tests, tissue
samples from the hippocampus and prefrontal cortex were obtained. The samples collected from
the hippocampus found that in the deaf-SA group the level of NR2B and PSD95, which are both
post-synaptic markers, as well as the pre-synaptic marker, synaptophysin, were significantly
lower while the other three groups saw no change. This data is indicative of cognitive
impairment being accelerated by the synergistic effects of hearing loss and Ab due to synaptic
loss (Chang et al., 2019).
Overall, the results of this study solidified the hypotheses of previous research in that
hearing loss might act as a risk factor for cognitive impairment in AD patients and that hearing
loss may cause hippocampal synapses to be more vulnerable to brain pathology (Chang et al.,
2019). It also demonstrated that there are in fact connections between the central auditory
pathway and the hippocampus (Chang et al., 2019).
2.
This study was conducted to determine if there is an association between hearing loss
and cognitive impairment. Previous studies done on modifiable risk factors associated with
developing Alzheimer’s disease did find a correlation between hearing loss and the development
of AD, but the etiology was unknown. There are some hypotheses on the exact mechanism of
action, the most predominant being that the loss of the ability to hear can result in isolation and
ultimately dementia (Ralli et al., 2019). Hearing loss in the elderly, also known as presbycusis,
impairs one’s ability to communicate and can lead to cognitive decline resulting in dementia
(Ralli et al., 2019). One of the earliest studies to determine the correlation between hearing loss
and AD was an observation study done by Uhlmann et al. The results found that, “hearing loss
was significantly and independently correlated with the severity of cognitive dysfunction” with
diagnosed AD patients having twice the rate of hearing loss as compared to the controls
(Uhlmann et al., 1986). However, prior to the current study, there was only epidemiological
evidence of a link between hearing loss and cognitive impairment. The aim of this study was to
expand that knowledge by using animal models to find the mechanism of action in which hearing
loss and resulting cognitive impairment actually occurred. The results of this study showed that
hearing loss may cause hippocampal synapses to be more vulnerable to brain pathology as shown
by the change in synaptic protein levels. This is a breakthrough because no previous studies
found any empirical evidence as to what the pathology behind the correlation in Alzheimer’s
disease and cognitive impairment. It also sets up the basis for future research and gives a
direction as to where to look for potential treatments to minimize hearing loss and its role in
damaging cognitive abilities.
3.
While this study was a breakthrough and a great stepping stone to future research, it
does have some limitations. The first is that this study was done solely on animal models. While
animal models are often indicative of what happens in humans, there is no guarantee that this is
the case for this study. In addition, in order to test the relation between hearing loss and cognitive
impairment, the researchers had to induce Ab deposition and hearing loss in the animal models.
In humans, development happens gradually, so this sudden onset could have modified the results.
More research would need to be done where the gradual onset could be mimicked more
accurately. Ultimately the goal would be to look at human models to see if there is the same type
of results. The results of this study also indicated that there was a decrease in the number of
hippocampal synapses after the animal model experienced hearing loss (Chang et al., 2019).
However, the study did not determine the location or role that these played in the impairment of
cognitive ability. Further studies done specifically on the location and role that the degenerated
synapse have could prove beneficial into understanding the full pathology behind hearing loss
and its role in AD and other cognitive disabilities.
A study conducted by Paciello et al. built off of the results of this study and others by
looking at the effect of auditory sensory deprivation in cognitive decline (Paciello et al., 2021).
Unlike the study done by Chang et al. this was done over time and more closely mimicked the
disease progression in humans. The study showed similar results with synaptic and
morphological changes in the auditory cortex (Paciello et al., 2021).
References:
Chang, M., Kim, H. J., Mook-Jung, I., & Oh, S.-ha. (2019). Hearing loss as a risk factor for
cognitive impairment and loss of synapses in the hippocampus. Behavioural Brain
Research, 372, 112069. https://doi.org/10.1016/j.bbr.2019.112069
Paciello, F., Rinaudo, M., Longo, V., Cocco, S., Conforto, G., Pisani, A., Podda, M. V., Fetoni,
A. R., Paludetti, G., & Grassi, C. (2021). Auditory sensory deprivation induced by noise
exposure exacerbates cognitive decline in a mouse model of alzheimer’s disease. ELife, 10.
https://doi.org/10.7554/elife.70908
Ralli, M., Gilardi, A., Stadio, A. D., Severini, C., Greco, A., Vincentiis, M. de, & Salzano, F.
(2019). Hearing loss and alzheimer?s disease: A Review. The International Tinnitus
Journal, 23(2), 79–85. https://doi.org/10.5935/0946-5448.20190014
Uhlmann, R. F., Larson, E. B., & Koepsell, T. D. (1986). Hearing impairment and cognitive
decline in senile dementia of the alzheimer’s type. Journal of the American Geriatrics
Society, 34(3), 207–210. https://doi.org/10.1111/j.1532-5415.1986.tb04204.x
Reply2:
The article Hearing Loss as a Risk Factor for Cognitive Impairment and Loss of Synpases in the
Hippocampus, by Munyoung Chang et al, looks at the possible affects of hearing loss on
cognitive impairment. To do this, they administered ameloid-ß (Aß) to animal models in order to
make their brain more vulnerable. From here, they were able to compare four groups with
exposure to differing levels of sound as well as Aß administration through cognitive function
testing as and synaptic protein measurements (Chang et al, 2019). Hearing loss is quite common
in the United States, impacting nearly one in every eight people with rates increasing with age
(U.S. Department: Quick Statistics, n.d.). Exposure to loud sounds, damage to the inner ear or
ear drum, brain damage, diabetes, stroke, certain medications as well as genetics may result in
varying degrees of hearing loss (U.S. Department: Hearing loss, n.d.). In this article, researchers
relate the cognitive effects of hearing loss to Alzheimers disease, a form of dementia affecting
more than six million people today (2021 Alzheimer’s, 2021), as hearing loss may put people at
higher risk for developing this life altering condition.
At the conclusion of the study, researchers found that the group with hearing loss and increased
Aß exposure had significantly decreased scores on cognitive tests than their hearing counterparts.
Researchers came to this finding due to various reasons. First, it was determined that at the 11
week mark, there was a significant decrease in the deaf group regarding cognitive function in
comparison to the other three groups. To add to this, the deaf-SA group also had significantly
lower scores for cognitive testing than the other three groups, particularly for the Y-maze, OPT
and OLT tests. Looking at synaptic protein levels of the brain, it was found that the hippocampus
showed decreased levels of post synaptic markers NR2B and PSD95 (Chang et al, 2019). These
post synaptic markers are responsible for maintaining working memory and cognitive flexibility
(Monaco et al, 2015) as well as regulates the location of various synapses (Jean et al, 2019),
respectively. PSD95 were also decreased in the prefrontal cortex (Chang et al, 2019).
While this study provided important information regarding hearing loss and cognitive function,
the mechanism is still unclear. With this study’s findings in mind, researchers hypothesized
hearing loss could negatively impact cognitive function in that it may increase cognitive load,
impact brain structures due to decreased cochlear stimulation and auditory signals, or be a result
of decreased social engagement from hearing loss (Chang et al, 2019). The change in cognitive
load and brain structures as causative agents in decreased cognitive function as it relates to
hearing loss has been hypothesized before. In the article, Hearing Loss and Cognitive
Impairment: Epidemiology, Common Pathophysiological Findings, and Treatment
Considerations, by Bisogno et al, the authors theorized that hearing loss required the brain to
work harder in order to process sound. This in turn could cause changes in brain structures, such
as working memory. As working memory is severely impacted in those with Alzheimer’s disease
(Jahn, 2013), the correlation made by Chang and their team would make sense.
I didn’t feel there was a specific novelty regarding the findings from this study as I was able to
find many other articles that found very similar results. That being said, the results from this
study are heavily supported by similar studies completed as others also found decreases in
PSD95 in the hippocampus and the possible connection between cognitive load, brain structure
and decreased cognitive function (Chang et al, 2019). While I would not say there was anything
overly novel regarding Chang et al’s findings, the quick decline in cognitive function at week 11
found by the Y-maze test is important as it demonstrates that there is a cognitive decline
happening even if the mechanism is not known (Chang et al, 2019). In order to better understand
the results from this study, a similar study would need to be done with human participants or a
different animal model that utilizes the Aß found to affect humans as that type was not used here.
This would provide a better connection between hearing loss, Aß and decreased cognitive
function. To add to this, the mechanism of how exactly hearing loss causes decreasing cognitive
function and thus impacts Alzheimer’s development needs to be further looked into. Although
the theories hypothesized can be backed up, there is still a lack of clear understanding. By
understanding the mechanism, researchers would then be able to come up with new treatments as
well as aware in the hopes of decreasing the amount of those not only impacted by hearing loss
related cognitive function, but by those may be facing Alzheimer’s disease as a result.
References:
2021 Alzheimer’s disease facts and figures. (2021). Alzheimer’s & dementia : the journal of the
Alzheimer’s Association, 17(3), 327–406. https://doi.org/10.1002/alz.12328
Jahn H. (2013). Memory loss in Alzheimer’s disease. Dialogues in clinical neuroscience, 15(4),
445–454. https://doi.org/10.31887/DCNS.2013.15.4/hjahn
Chang, M., Kim, H. J., Mook-Jung, I., & Oh, S. H. (2019). Hearing loss as a risk factor for
cognitive impairment and loss of synapses in the hippocampus. Behavioural brain research, 372,
112069. https://doi.org/10.1016/j.bbr.2019.112069
Jeong, J., Pandey, S., Li, Y., Badger, J. D., Lu, W., & Roche, K. W. (2019). PSD-95 binding
dynamically regulates NLGN1 trafficking and function. Proceedings of the National Academy of
Sciences, 116(24), 12035–12044. https://doi.org/10.1073/pnas.1821775116
Monaco, S. A., Gulchina, Y., & Gao, W. J. (2015). NR2B subunit in the prefrontal cortex: A
double-edged sword for working memory function and psychiatric disorders. Neuroscience and
biobehavioral reviews, 56, 127–138. https://doi.org/10.1016/j.neubiorev.2015.06.022
U.S. Department of Health and Human Services. (n.d.). Hearing loss: A common problem for
older adults. National Institute on Aging. Retrieved July 21, 2022, from
https://www.nia.nih.gov/health/hearing-loss-common-problem-older-adults#causes
U.S. Department of Health and Human Services. (n.d.). Quick statistics about hearing. National
Institute of Deafness and Other Communication Disorders. Retrieved July 21, 2022, from
https://www.nidcd.nih.gov/health/statistics/quick-statistics-hearing
Read Less

Purchase answer to see full
attachment