Memory Changes in Normal and Pathological Aging

Abstract Purpose To assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process. Materials and Methods 277 functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson’s correlation was used to characterize the functional connectivity (FC) between caudate and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4 and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region’s connectivity with caudate. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI. Results The MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P=6.23x10−7, right: P=3.37x10−8), but not for men (P>0.3 for bilateral caudate). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI. Conclusion Sex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.

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AGING AND COGNITIVE DISORDERS FROM THE SOMNOLOGY’S VIEWPOINT

Успехи геронтологии ◽

10.34922/ae.2021.34.2.002 ◽

2021 ◽

pp. 195-201

Author(s):

И.М. Мадаева ◽

Н.В. Семенова ◽

Л.И. Колесникова ◽

С.И. Колесников

Keyword(s):

Sleep Disorders ◽

Cognitive Dysfunction ◽

Functional State ◽

Aging Process ◽

Cognitive Disorders ◽

Biologically Active ◽

Cell Markers ◽

Social Burden ◽

Pathological Aging ◽

Age Related

Высокое социальное бремя возрастзависимых заболеваний делает актуальным разработку и внедрение комплекса медицинских технологий донозологической диагностики, лечения и профилактики различных нарушений функциональных состояний жизнедеятельности человека в процессе старения. Возрастное снижение активности функционального состояния мозга и его взаимообусловленность с континуумом сон-бодрствование приводит к преждевременному (патологическому) старению с проявлениями нейродегенерации. Хотя нарушения функционирования цикла сон-бодрствование являются характерными для процесса старения, но возрастные изменения не всегда сопровождаются когнитивной дисфункцией. Сложная архитектура сна претерпевает выраженные изменения в течение всей жизни человека. В литературе активно дискутируется взаимосвязь нарушений циркадной ритмики при старении и развития когнитивной дисфункции. В то же время встречается достаточное количество исследований, посвященных изменениям организма на молекулярном уровне при возрастных нарушениях сна. Гетерогенность патогенетических механизмов старения, ассоциаций нарушений сна и процессов когнитивной дисфункции включает также изменение метаболизма. В регуляцию процессов сна вовлечены различные нейромедиаторы и другие биологически активные вещества, так называемые «sleep-promoting substances». Насущная необходимость дальнейших научных изысканий в поиске молекулярно-клеточных маркеров и диагностических паттернов нарушений сна при старении является перспективным и внесет значительный вклад в развитие прорывных технологий в профилактике патологического старения. Подход с позиции современной нейробиологии, сомнологии и медицины сна представляется крайне актуальным и своевременным. Этот обзор посвящен некоторым аспектам научных изысканий, посвященных возрастным изменениям сна и их молекулярно-клеточным маркерам. Age-dependent diseases high social burden makes relevant medical technologies development and implementation of human aging process functional state various disorders prenosological diagnosis, treatment and prevention. Age-related activity decrease of the brain functional state and its interdependence with the sleep-wake continuum leads to premature (pathological) aging with manifestations of neurodegeneration. Although disturbances of the sleep-wake cycle functioning are characteristic for the aging process, age-related changes are not always accompanied by cognitive dysfunction. There are sufficient number studies on the molecular level changes in age-related sleep disorders. Aging, sleep disorders and processes of cognitive dysfunction association pathogenetic mechanisms heterogeneity also include metabolism changes. Various neurotransmitters and other biologically active substances, so-called «sleep-promoting substances» are involved in the regulation of sleep processes. The urgent need for molecular-cell markers and diagnostic patterns of sleep disorders further scientific search in aging process is promising and will make a significant contribution to the breakthrough technologies development in the pathological aging prevention. The complex architecture of sleep undergoes pronounced changes throughout a person’s life. In the literature, the relationship of circadian rhythm disturbances during aging and the development of cognitive dysfunction is actively debated. Approach from the positions of the modern neurobiology, somnology and sleep medicine perspectives seems extremely relevant and timely. This review is devoted to some aspects of age-related in sleep and their molecular-cell markers changes modern scientific research and our own data analysis.

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Pathological Aging

Aging and Behavior ◽

10.1007/978-3-662-38517-3_8 ◽

1984 ◽

pp. 129-142

Author(s):

Jack Botwinick

Keyword(s):

Pathological Aging

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Semantic Processing in Healthy Aging and Alzheimer’s Disease: A Systematic Review of the N400 Differences

Brain Sciences ◽

10.3390/brainsci10110770 ◽

2020 ◽

Vol 10 (11) ◽

pp. 770

Author(s):

Marilyne Joyal ◽

Charles Groleau ◽

Clara Bouchard ◽

Maximiliano A. Wilson ◽

Shirley Fecteau

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Semantic Processing ◽

Healthy Aging ◽

Semantic Knowledge ◽

Event Related Potential ◽

N400 Effect ◽

Pathological Aging ◽

Healthy Elderly

Semantic deficits are common in individuals with Alzheimer’s disease (AD). These deficits notably impact the ability to understand words. In healthy aging, semantic knowledge increases but semantic processing (i.e., the ability to use this knowledge) may be impaired. This systematic review aimed to investigate semantic processing in healthy aging and AD through behavioral responses and the N400 brain event-related potential. The results of the quantitative and qualitative analyses suggested an overall decrease in accuracy and increase in response times in healthy elderly as compared to young adults, as well as in individuals with AD as compared to age-matched controls. The influence of semantic association, as measured by N400 effect amplitudes, appears smaller in healthy aging and even more so in AD patients. Thus, semantic processing differences may occur in both healthy and pathological aging. The establishment of norms of healthy aging for these outcomes that vary between normal and pathological aging could eventually help early detection of AD.

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Animal Models of Pathological Aging

The Wiley Handbook on the Aging Mind and Brain ◽

10.1002/9781118772034.ch4 ◽

2018 ◽

pp. 61-77

Author(s):

Eric B. Emmons ◽

Youngcho Kim ◽

Nandakumar S. Narayanan

Keyword(s):

Animal Models ◽

Pathological Aging

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A Review and Reappraisal of the Default Network in Normal Aging and Dementia

Oxford Research Encyclopedia of Psychology ◽

10.1093/acrefore/9780190236557.013.384 ◽

2019 ◽

Cited By ~ 3

Author(s):

Jessica R. Andrews-Hanna ◽

Matthew D. Grilli ◽

Muireann Irish

Keyword(s):

Older Adults ◽

Cognitive Function ◽

Brain Aging ◽

Strong Support ◽

Well Being ◽

Normal Aging ◽

Aging Brain ◽

Default Network ◽

Pathological Aging ◽

Age Related

The brain’s default network (DN) has received considerable interest in the context of so-called “normal” and pathological aging. Findings have generally been couched in support of a pessimistic view of brain aging, marked by substantial loss of structural brain integrity accompanied by a host of impairments in brain and cognitive function. A critical look at the literature, however, reveals that the standard loss of integrity, loss of function (LILF) view in normal aging may not necessarily hold with respect to the DN and the internally guided functions it supports. Many internally guided processes subserved by the DN are preserved or enhanced in cognitively healthy older adults. Moreover, differences in motivational, contextual, and physiological factors between young and older adults likely influence the extant neuroimaging and cognitive findings. Accordingly, normal aging can be viewed as a series of possibly adaptive cognitive and DN-related alterations that bolster cognitive function and promote socioemotional well-being and stability in a stage of life noted for change. On the other hand, the available evidence reveals strong support for the LILF view of the DN in neurodegenerative disorders, whereby syndromes such as Alzheimer’s disease (AD) and semantic dementia (SD), characterized by progressive atrophy to distinct DN subsystems, display distinct aberrations in autobiographical and semantic cognition. Taken together, these findings call for more naturalistic, age-appropriate, and longitudinal paradigms when investigating neurocognitive changes in aging and to adequately assess and control for differences in non-neural factors that may obscure “true” effects of normal and pathological aging. A shift in the framework with which age-related alterations in internally guided cognition are interpreted may shed important light on the neurocognitive mechanisms differentiating healthy and pathological aging, leading to a more complete picture of the aging brain in all its complexity.

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