Reported Hearing Loss in Alzheimer’s Disease Is Associated With Loss of Brainstem and Cerebellar Volume

Llano, Daniel A.; Kwok, Susanna S.; Devanarayan, Viswanath

doi:10.3389/fnhum.2021.739754

Cited by 11 publications

(17 citation statements)

References 54 publications

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“…Strikingly, the poorer cognitive performance in MMC residents was associated with caudate and left orbital gyrus atrophy in keeping with orbital frontal cortex connections with regions processing visual, spatial, emotional information and social cognition, PFCcaudate brain wiring, and caudate functions affecting learning, memory, reward and motivation [69][70][71][72][73][74]. The current findings are not unexpected, i.e., the cerebellar atrophy is significant and could have a clinical counterpart in gait and equilibrium abnormalities described by our group in young MMC urbanites [75], cognitive deficits [16,57], the association between hearing loss and decreased brainstem and cerebellar volumes in AD cases [76], and gait and cognitive abnormalities associated with regional cerebellar atrophy in elderly fallers [77]. Cerebellar atrophy is particularly intriguing in view of our published cerebellar higher concentrations of magnetite (estimated from their saturation remanent magnetisation (SIRM) values) in MMC young forensic cases [2] and the recent description of regional cerebellar hypermetabolism in AD [78].…”

Section: Discussionsupporting

confidence: 64%

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution

Calderón‐Garcidueñas

Hernández-Luna²,

Mukherjee

et al. 2022

Toxics

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Exposures to fine particulate matter PM2.5 are associated with Alzheimer’s, Parkinson’s (AD, PD) and TDP-43 pathology in young Metropolitan Mexico City (MMC) residents. High-resolution structural T1-weighted brain MRI and/or Montreal Cognitive Assessment (MoCA) data were examined in 302 volunteers age 32.7 ± 6.0 years old. We used multivariate linear regressions to examine cortical surface area and thickness, subcortical and cerebellar volumes and MoCA in ≤30 vs. ≥31 years old. MMC residents exposed to PM2.5 ~ 30.9 µg/m3. Robust hemispheric differences in frontal and temporal lobes, caudate and cerebellar gray and white matter and strong associations between MoCA total and index scores and caudate bilateral volumes, frontotemporal and cerebellar volumetric changes were documented. MoCA LIS scores are affected early and low pollution controls ≥ 31 years old have higher MoCA vs. MMC counterparts (p ≤ 0.0001). Residency in MMC is associated with cognitive impairment and overlapping targeted patterns of brain atrophy described for AD, PD and Fronto-Temporal Dementia (FTD). MMC children and young adult longitudinal studies are urgently needed to define brain development impact, cognitive impairment and brain atrophy related to air pollution. Identification of early AD, PD and FTD biomarkers and reductions on PM2.5 emissions, including poorly regulated heavy-duty diesel vehicles, should be prioritized to protect 21.8 million highly exposed MMC urbanites.

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Section: Discussionsupporting

confidence: 64%

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution

Calderón‐Garcidueñas

Hernández-Luna²,

Mukherjee

et al. 2022

Toxics

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“…Recent studies suggest that hearing loss causes brain changes that raise the risk for AD. Individuals with moderate to severe hearing loss are up to five times as likely to develop AD-associated dementia, though more research is needed to determine the exact connection between sound, hearing loss, and AD [ 134 , 135 , 136 ].…”

Section: Multiple Strategies To Optimize Brain Healthmentioning

confidence: 99%

Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review

Rao¹,

Subramaniam

Gregory³

et al. 2023

IJMS

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Alzheimer’s disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in overall cognitive function. Usually manifesting in individuals over the age of 60, this is the most prevalent type of dementia and remains the fifth leading cause of death among Americans aged 65 and older. While the development of effective treatment and prevention for AD is a major healthcare goal, unfortunately, therapeutic approaches to date have yet to find a treatment plan that produces long-term cognitive improvement. Drugs that may be able to slow down the progression rate of AD are being introduced to the market; however, there has been no previous solution for preventing or reversing the disease-associated cognitive decline. Recent studies have identified several factors that contribute to the progression and severity of the disease: diet, lifestyle, stress, sleep, nutrient deficiencies, mental health, socialization, and toxins. Thus, increasing evidence supports dietary and other lifestyle changes as potentially effective ways to prevent, slow, or reverse AD progression. Studies also have demonstrated that a personalized, multi-therapeutic approach is needed to improve metabolic abnormalities and AD-associated cognitive decline. These studies suggest the effects of abnormalities, such as insulin resistance, chronic inflammation, hypovitaminosis D, hormonal deficiencies, and hyperhomocysteinemia, in the AD process. Therefore a personalized, multi-therapeutic program based on an individual’s genetics and biochemistry may be preferable over a single-drug/mono-therapeutic approach. This article reviews these multi-therapeutic strategies that identify and attenuate all the risk factors specific to each affected individual. This article systematically reviews studies that have incorporated multiple strategies that target numerous factors simultaneously to reverse or treat cognitive decline. We included high-quality clinical trials and observational studies that focused on the cognitive effects of programs comprising lifestyle, physical, and mental activity, as well as nutritional aspects. Articles from PubMed Central, Scopus, and Google Scholar databases were collected, and abstracts were reviewed for relevance to the subject matter. Epidemiological, pathological, toxicological, genetic, and biochemical studies have all concluded that AD represents a complex network insufficiency. The research studies explored in this manuscript confirm the need for a multifactorial approach to target the various risk factors of AD. A single-drug approach may delay the progression of memory loss but, to date, has not prevented or reversed it. Diet, physical activity, sleep, stress, and environment all contribute to the progression of the disease, and, therefore, a multi-factorial optimization of network support and function offers a rational therapeutic strategy. Thus, a multi-therapeutic program that simultaneously targets multiple factors underlying the AD network may be more effective than a mono-therapeutic approach.

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“…This hypothesis is mainly based on the ability of cerebral hypoperfusion, caused by cortical microinfarcts, to exacerbate a cognitive decline in AD [ 24 ]. On the other hand, many epidemiological studies have shown the link between ARHL and AD associated with the loss of the brainstem and cerebellar volume [ 25 ]. Moreover, this biomarker has been established for various cardiovascular and cerebrovascular pathologies, including congenital heart disease, stroke and carotid stenosis [ 24 , 26 , 27 ].…”

Section: Introduction: Alzheimer’s Disease—etiology and Pathophysiologymentioning

confidence: 99%

Linking Cerebrovascular Dysfunction to Age-Related Hearing Loss and Alzheimer’s Disease—Are Systemic Approaches for Diagnosis and Therapy Required?

et al. 2022

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Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction, cognitive decline, and the accumulation of amyloid β peptide (Aβ) in the brain and tau-related lesions in neurons termed neurofibrillary tangles (NFTs). Aβ deposits and NFT formation are the central pathological hallmarks in AD brains, and the majority of AD cases have been shown to exhibit a complex combination of systemic comorbidities. While AD is the foremost common cause of dementia in the elderly, age-related hearing loss (ARHL) is the most predominant sensory deficit in the elderly. During aging, chronic inflammation and resulting endothelial dysfunction have been described and might be key contributors to AD; we discuss an intriguing possible link between inner ear strial microvascular pathology and blood–brain barrier pathology and present ARHL as a potentially modifiable and treatable risk factor for AD development. We present compelling evidence that ARHL might well be seen as an important risk factor in AD development: progressive hearing impairment, leading to social isolation, and its comorbidities, such as frailty, falls, and late-onset depression, link ARHL with cognitive decline and increased risk of dementia, rendering it tempting to speculate that ARHL might be a potential common molecular and pathological trigger for AD. Additionally, one could speculate that amyloid-beta might damage the blood–labyrinth barrier as it does to the blood–brain barrier, leading to ARHL pathology. Finally, there are options for the treatment of ARHL by targeted neurotrophic factor supplementation to the cochlea to improve cognitive outcomes; they can also prevent AD development and AD-related comorbidity in the future.

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Reported Hearing Loss in Alzheimer’s Disease Is Associated With Loss of Brainstem and Cerebellar Volume

Cited by 11 publications

References 54 publications

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution

Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review

Linking Cerebrovascular Dysfunction to Age-Related Hearing Loss and Alzheimer’s Disease—Are Systemic Approaches for Diagnosis and Therapy Required?

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