Decoding brain aging trajectory: predictive discrepancies, genetic susceptibilities, and emerging therapeutic strategies

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: March 19, 2025

The global extension of human lifespan has intensified the focus on aging, yet its underlying mechanisms remain inadequately understood. article highlights aspects genetic susceptibility to impaired brain bioenergetics, trends in age-related gene expression related neuroinflammation and senescence, impact stem cell exhaustion quiescence accelerated aging. We also review accumulation senescent cells, mitochondrial dysfunction, metabolic disturbances as central pathological processes emphasizing how these factors contribute inflammation disrupt cellular competition defining aging trajectory. Furthermore, we discuss emerging therapeutic strategies future potential integrating advanced technologies refine assessments. combination several methods including analysis, neuroimaging techniques, cognitive tests digital twins, offer a novel approach by simulating monitoring individual health trajectories, thereby providing more accurate personalized insights. Conclusively, estimation trajectories is crucial for understanding managing processes, potentially transforming preventive improve outcomes populations.

Language: Английский

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Expanding the Applicability of Cognitive Charts to the Entire Age Span

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 327 - 327

Published: March 21, 2025

Background/Objectives: We previously developed Cognitive Charts (CCs) for early detection and/or longitudinal evaluation of age-associated cognitive decline on widely used screening measures such as the Mini-Mental State Examination (CC-MMSE) and Montreal Assessment (CC-MoCA). Similar to growth curves in Pediatrics, clinicians can quickly interpret an individual's performance MMSE or MoCA, track patient's trajectory, subsequently intervene earlier based findings (see quoco.org). This has proven very helpful frontline clinicians, particularly light newly approved monoclonal antibodies treatment Alzheimer's disease. To this date, however, CC-MMSE CC-MoCA only applied limited age ranges. validated herein our CCs across entire span. Methods: Two datasets were obtained from National Coordinating Center, a total 32,560 individuals. examined average MoCA scores younger individuals compared current thresholds ensured consistency age-related Quotient scores. Results: In study, both show little variation below threshold. If is fixed at threshold QuoCo calculation, resulting score remains constant within range. Furthermore, performed similar better Conclusions: Our again emphasize clinical significance tool monitoring changes span, hence maximizing appropriate monitoring.

Language: Английский

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Healthy aging delays and dedifferentiates high-level visual representations

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Healthy aging impacts visual information processing with consequences for subsequent high-level cognition and everyday behavior, but the underlying neural changes in representations remain unknown. Here, we investigate nature of object recognition older compared to younger adults by tracking them time using electroencephalography (EEG), across space functional magnetic resonance imaging (fMRI), probing their behavioral relevance similarity judgments. Applying a multivariate analysis framework combine experimental assessments, four key findings about how brain emerge. First, selectively delays formation representations, profoundly changing chronometry processing. Second, delay emerges rather than low- mid-level ventral cortex, supporting theory that areas developing last deteriorate first. Third, reduces content selectivity indicating age-related dedifferentiation as mechanism representational change. Finally, demonstrate identified are behaviorally relevant, ascertaining ecological relevance. Together, our results reveal impact healthy on brain.

Language: Английский

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Entorhinal cortex–hippocampal circuit connectivity in health and disease

Frontiers in Human Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Sept. 20, 2024

The entorhinal cortex (EC) and hippocampal (HC) connectivity is the main source of episodic memory formation consolidation. entorhinal–hippocampal (EC-HC) connection classified as canonically glutamatergic and, more recently, has been characterized a non-canonical GABAergic connection. Recent evidence shows that both EC HC receive inputs from dopaminergic, cholinergic, noradrenergic projections modulate mnemonic processes linked to encoding consolidation memories. In present review, we address latest findings on EC-HC role neuromodulations during mechanisms memories highlight value cross-species approach unravel underlying cellular known. Furthermore, discuss how early neurodegeneration may contribute dysfunction observed in aging Alzheimer’s disease (AD). Finally, described exercise be fundamental tool prevent or decrease neurodegeneration.

Language: Английский

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Healthy aging delays and dedifferentiates high-level visual representations

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 30, 2024

1. Abstract Healthy aging impacts visual information processing with consequences for subsequent high-level cognition and everyday behavior, but the underlying neural changes in representations remain unknown. Here, we investigate nature of object recognition older compared to younger adults by tracking them time using EEG, across space fMRI, probing their behavioral relevance similarity judgements. Applying a multivariate analysis framework combine experimental assessments, four key findings about how brain emerge. First, selectively delays formation representations, profoundly changing chronometry processing. Second, delay emerges rather than low- mid-level ventral cortex, supporting theory that areas developing last deteriorate first. Third, reduces content selectivity indicating age-related dedifferentiation as mechanism representational change. Finally, demonstrate identified are behaviorally relevant, ascertaining ecological relevance. Together, our results reveal impact healthy on brain.

Language: Английский

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Contrastive machine learning reveals Parkinson’s disease specific features associated with disease severity and progression

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Aug. 7, 2024

Parkinson's disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients 366 controls, aiming disentangle PD-specific The results reveal that these alterations are correlated with individual differences dopamine transporter binding deficit, neurodegeneration biomarkers, clinical severity progression. correlation is verified an external cohort. Notably, certain proteins the cerebrospinal fluid strongly associated features, particularly those involved immune function. most notable observed both subcortical temporal regions. Our findings provide deeper insights into patterns brain atrophy potential underlying molecular mechanisms, paving way for earlier patient stratification development treatments slow down neurodegeneration. A analysis MRI this revealed alterations, primarily regions, which correlate severity, immunerelated proteins.

Language: Английский

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Environmental enrichment in middle age rats improves spatial and object memory discrimination deficits

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 17, 2024

Changes in memory performance are one of the main symptoms normal aging. The storage similar experiences as different memories (ie. behavioral pattern separation), becomes less efficient aging progresses. Studies have focused on hippocampus dependent spatial and their role related deficits separation (BPS) by targeting high similarity interference conditions. However, parahippocampal cortices such perirhinal cortex also particularly vulnerable to Middle age is thought be stage where mild mnemonic begin emerge. Therefore, a better understanding timing object domain impairment could shed light over how plasticity changes parahipocampal-hippocampal system affects function early In present work, we compared young middle-aged rats both (spontaneous location recognition) non-spatial tasks understand comparative progression these from stages Moreover, explored impact environmental enrichment (EE) an intervention with important translational value. Although bulk studies examined contribution EE for preventing decline diverse cognitive domains, there limited knowledge this specifically BPS animals. Here evaluate effects modulator BPS, its ability revert caused at stages. We reveal domain-dependent rats, affected independently only when stimuli similar, effect that linked higher seen group. found significantly enhanced domain, improvement specific load condition. conclusion, results suggest differentially but responsive multidomain manner.

Language: Английский

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The effect of feedback timing on category learning and feedback processing in younger and older adults

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: June 3, 2024

Introduction Corrective feedback can be received immediately after an action or with a temporal delay. Neuroimaging studies suggest that immediate and delayed are processed by the striatum medial lobes (MTL), respectively. Age-related changes in MTL may influence efficiency of feedback-based learning older adults. The current study leverages event-related potentials (ERPs) to evaluate age-related differences processing consequences for learning. feedback-related negativity (FRN) captures activity frontostriatal circuit while N170 is hypothesized reflect activation. Methods 18 younger ( M years = 24.4) 20 65.5) adults completed tasks feedback. For each group, outcomes ERP magnitudes were evaluated across timing conditions. Results Younger learned better than condition. This performance difference was associated typical FRN signature but not adults, impaired have negatively impacted Conversely, comparable groups when delayed. both groups, larger magnitude relative feedback, suggesting greater Discussion conclusion Delaying increase involvement and, improve category neural differentially affect MTL- striatal-dependent Future research locus how manipulated optimize lifespan.

Language: Английский

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Less spatial exploration is associated with poorer spatial memory in midlife adults

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: June 11, 2024

Introduction Despite its importance for navigation, very little is known about how the normal aging process affects spatial exploration behavior. We aimed to investigate: (1) behavior may be altered early in process, (2) relationship between and subsequent memory, (3) whether can classify participants according age. Methods Fifty healthy young (aged 18–28) 87 midlife adults 43–61) freely explored a desktop virtual maze, learning locations of nine target objects. Various behaviors (object visits, distance traveled, turns made, etc.) were measured. In test phase, navigated from one object another without feedback, their wayfinding success (% correct trials) was Results exhibited less overall compared adults, prioritized over maze layout. when adults. Furthermore, following principal components analysis (PCA), regression analyses indicated that both quantity quality associated with group, but not Finally, we could age similar accuracy using either or scores. Discussion Our results aid understanding impacts exploration, encourages future investigations into pathological affect

Language: Английский

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Lifespan Oscillatory Dynamics in Lexical Production: A Population-based MEG Resting-State Analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Lexical production remains relatively preserved across the lifespan, but cognitive control demands increase with age to support efficient semantic access. It suggests a domain-general and language-specific component. Current neurocognitive models suggest Default Mode Network (DMN) may drive interplay between these components, impacting trajectory of performance pivotal shift around midlife. However, corresponding time-varying architecture still needs clarification. Here, we leveraged MEG resting-state data from healthy adults aged 18-88 CamCAN population-based sample. We found that DMN temporal dynamics anterior-ventral posterior-dorsal states until midlife mitigate word-finding challenges. Similarly, sensorimotor integration along this posterior path enhances cross-talk lower-level circuitry as dynamic information flow more anterior, higher-order gets compromised. bottom-up, exploitation-based form in aging brain, highlighting abstraction, control, perceptive-motor systems preserving lexical production.

Language: Английский

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