Aging Brain and Hearing: A Mini-Review

Brain reserve is a topic of great interest to researchers in aging medicine field. Some individuals retain well-preserved cognitive function until they fulfill their lives despite significant brain pathology. One concept that explains this paradox is the reserve hypothesis, including brain reserve that assumes a virtual ability to mitigate the effects of neuropathological changes and reduce the effects on clinical symptoms flexibly and efficiently by making complete use of the cognitive and compensatory processes. One of the surrogate measures of reserve capacity is brain volume. Evidence that dementia and hearing loss are interrelated has been steadily accumulating, and age-related hearing loss is one of the most promising modifiable risk factors of dementia. Research focused on the imaging analysis of the aged brain relative to auditory function has been gradually increasing. Several morphological studies have been conducted to understand the relationship between hearing loss and brain volume. In this mini review, we provide a brief overview of the concept of brain reserve, followed by a small review of studies addressing brain morphology and hearing loss/hearing compensation, including the findings obtained from our previous study that hearing loss after middle age could affect hippocampal and primary auditory cortex atrophy.

Associations between Brain Reserve Proxies and Clinical Progression in Alzheimer’s Disease Dementia

The purpose of this study was to investigate whether brain and cognitive reserves were associated with the clinical progression of AD dementia. We included participants with AD dementia from the Alzheimer’s Disease Neuroimaging Initiative, provided they were followed up at least once, and candidate proxies for cognitive (education for early-life reserve and Adult Reading Test for late-life reserve) or brain reserve (intracranial volume [ICV] for early-life reserve and the composite value of [18F] fluorodeoxyglucose positron emission tomography regions of interest (FDG-ROIs) for late-life reserve) were available. The final analysis included 120 participants. Cox proportional hazards model revealed that FDG-ROIs were the only significant predictor of clinical progression. Subgroup analysis revealed a significant association between FDG-ROIs and clinical progression only in the larger ICV group (HR = 0.388, p = 0.028, 95% CI 0.167–0.902). Our preliminary findings suggest that relatively preserved cerebral glucose metabolism might delay further clinical progression in AD dementia, particularly in the greater ICV group. In addition to ICV, cerebral glucose metabolism could play an important role as a late-life brain reserve in the process of neurodegeneration. Distinguishing between early- and late-life reserves, and considering both proxies simultaneously, would provide a wider range of factors associated with the prognosis of AD dementia.

Regional Brain Volume, Brain Reserve and MMSE Performance in Healthy Aging From the NEUROAGE Cohort: Contributions of Sex, Education, and Depression Symptoms

Objective: The aim of this study was twofold. First, to investigate the relationship between age, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes, brain reserve (BR), and specific regions of interest (ROIs) with global cognitive function in healthy older adults participating in a longitudinal study on aging in the island country of Cyprus. Second, to assess the contribution of important demographic and psychosocial factors on brain volume. Specifically, the effects of sex and years of education and the association between depression symptoms on brain volume were also explored in this Mediterranean cohort.Methods: Eighty-seven healthy older adults (males = 37, females = 50) scoring ≥24 on the Mini-Mental State Examination (MMSE) were included, with a mean age of 72.75 years and a mean educational level of 10.48 years. The Geriatric Depression Scale was used to assess depression. T1-weighted magnetic resonance images were used to calculate global and regional volumes.Results: Age was negatively correlated with GM, WM, BR, MMSE scores, and ROIs, including the hippocampus, amygdala, entorhinal cortex, prefrontal cortex, anterior cingulate gyrus, and positively with CSF. Higher MMSE scores positively correlated with GM volume. Women exhibited greater levels of depression than men. Depression was also negatively correlated with GM volume and MMSE scores. Men had greater ventricular size than women and participants with higher education had greater ventricular expansion than those with fewer years in education.Conclusions: The reported structural changes provide evidence on the overlap between age-related brain changes and healthy cognitive aging and suggest that these age changes affect certain regions. Furthermore, sex, depressive symptomatology, and education are significant predictors of the aging brain. Brain reserve and higher education accommodate these changes and works against the development of clinical symptoms.

Motivational Reserve

Brain reserve (i.e., the ability of the brain to tolerate age- and disease-related changes in a way that cognitive function is still maintained) is assumed to be based on the lifelong training of various abilities. Motivational reserve (MR) is a form of brain reserve and can be defined as a set of motivational abilities that provide the individual with resilience to neuropathological damage. The first part of the chapter explains the term motivational processes and the model of MR and describes the measurement concept. The second part summarizes the results of several studies on the model of MR. For example, motivational abilities have been shown to be associated with a reduced risk of mild cognitive impairment and Alzheimer disease (AD) in apolipoprotein E ɛ4 carriers, but not in noncarriers. Revealing the mechanisms underlying the association of motivational abilities and cognitive decline may lead to novel strategies for delaying the onset of AD symptoms.

A-69 Baseline Predictors of Longitudinal SDMT Performance in Individuals with Multiple Sclerosis

Objective More than half of persons with MS (PwMS) experience cognitive difficulties during the course of their illness. However, not everyone develops cognitive problems suggesting a role for important moderating factors. The object of the current study was to identify baseline predictors of cognitive trajectories in PwMS. Methods 680 PwMS completed the Symbol Digit Modalities Test (SDMT) and a battery of patient-reported outcome (PRO) measures as part their participation in The Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB). Each participant had at least 2 SDMT measurements as well as demographic (age, sex), clinical (EDSS, disease duration, course type), and PRO (fatigue, depression, and quality of life) data. Participants had a concurrent brain MRI scan at the time of the baseline SDMT measurement; intracranial cavity (ICC) was calculated for each participant as a proxy of brain reserve. The association between each baseline measure and the longitudinal change in the SDMT over the course of the follow-up period was calculated using a linear mixed effects model. Results Increased baseline age (95% CI: −0.29, −0.06; p = 0.002), increased baseline EDSS (95% CI: −0.24, −0.01; p = 0.037), and decreased baseline ICC (95% CI: 0.02, 0.25; p = 0.023) were each associated with a greater decline in the SDMT score longitudinally. Although most PRO measures were cross-sectionally correlated with SDMT performance, none were associated with longitudinal change. Discussion Older individuals and those with more clinical disability are likely to experience declines in SDMT performance over time. Individuals with high baseline brain reserve tend to have more favorable SDMT trajectories.

Living Longer Better

Ageing is not a cause of major problems till the later nineties. The problems we fear—dementia, disability, and dependency are due to three other processes: loss of physical fitness, which starts long before old age, diseases, many of which are preventable, and pessimistic attitudes. Both lay people and our professional colleagues have difficulty with the meanings of dementia, Alzheimer’s disease, vascular dementia, and cognitive ageing and use these terms in different ways, often incorrectly. Now is the time to use your assets—preserving and increasing your brain reserve to reduce your risk of dementia. The fitness gap can be closed at any age by increasing both physical and social activity. There is no upper age limit for prevention. The steps we recommend for reducing the risk of dementia will also help you reduce the risk of other diseases, keep you fitter, and help you feel better, and are equally relevant for people who have already developed mild cognitive impairment or dementia.

The bidirectional causal effects of brain morphology across the life course and risk of Alzheimers disease: A cross-cohort comparison and Mendelian randomization meta-analysis

Neuropathological changes associated with Alzheimers disease (AD) can occur decades before clinical symptoms. We investigated whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or accelerating brain atrophy, respectively. We used bidirectional two-sample Mendelian randomization to estimate the effects of genetic liability to AD on global and regional cortical thickness, total intracranial volume, volume of subcortical structures and cerebral white matter in 36,842 participants aged eight to 81 years across five independent cohorts, and the effects of global and regional cortical thickness and subcortical volumes on AD risk in 94,337 participants. Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. We also found little evidence to suggest brain morphology alters AD risk. Thus, genetic liability to AD is likely to alter mechanisms and/or rates of neurodegeneration, rather than reduce structural brain reserve.