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Brain Sciences
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Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease
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Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Cognitive, Social and Affective Neuroscience".

Deadline for manuscript submissions: 15 January 2026 | Viewed by 1090

Special Issue Editors

Dr. Yuta Katsumi

E-Mail Website
Guest Editor
Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Interests: Alzheimer’s disease; brain networks; cognitive neuroscience; episodic memory; frontotemporal lobar degeneration; functional neuroimaging; hippocampus; mul-timodal neuroimaging; social cognition
Dr. Deepti Putcha

E-Mail Website
Guest Editor
Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Interests: atypical Alzheimer’s disease; posterior cortical atrophy
Special Issues, Collections and Topics in MDPI journals
Dr. Bradford C. Dickerson

E-Mail Website
Guest Editor
Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Interests: Alzheimer's disease; frontotemporal dementia; memory disorders; posterior corti-cal atrophy; primary progressive aphasia; the interface of neurological and psychi-atric illnesses; cognitive neuroscience; affective neuroscience; cognitive aging

Special Issue Information

Dear Colleagues,

Human cognitive aging is characterized by considerable heterogeneity across individuals. While some maintain cognitive resilience well into their late adulthood, others experience age-related cognitive decline due to complex interactions between genetic, environmental, and lifestyle factors. Heterogeneity in the type and severity of cognitive impairment also exists among those individuals who report subjective cognitive decline or who develop the initial symptoms of neurodegenerative diseases such as Alzheimer’s disease, highlighting the need to develop tools with improved diagnostic and prognostic utility. Understanding the factors that can predict and potentially modify the course of brain and cognitive aging across the continuum from healthy aging to neurodegenerative disease remains a major goal in neuroscience research. This Special Issue invites original research articles, reviews, and perspectives that explore the multifaceted nature of cognitive aging through the lens of biomarker assessments (e.g., neuroimaging, CSF, blood-based), novel experimental paradigms, digital assessments, and other aspects of within- or between-individual variability in affective, social, behavioral, or clinical measures. We particularly encourage submissions that advance our understanding of diverse aging trajectories and inform therapeutic interventions aimed at promoting healthy cognitive aging and mitigating neurodegenerative disease risk through a variety of methods, including neuromodulation, neurofeedback, cognitive training, or disease-modifying therapies.

Dr. Yuta Katsumi
Dr. Deepti Putcha
Dr. Bradford C. Dickerson
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aging
  • cognition
  • cognitive impairment
  • subjective cognitive decline
  • neurodegeneration
  • Alzheimer’s disease
  • prognostication
  • brain imaging
  • neuromodulation
  • interventions

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Published Papers (2 papers)

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Research

18 pages, 2255 KB  
Article
Putamen Stiffness Declines with Age and Is Associated with Implicit Sequence Learning Outcomes
by Hyeon Jung Heselton, Aaron T. Anderson, Curtis L. Johnson, Neal J. Cohen, Bradley P. Sutton and Hillary Schwarb
Brain Sci. 2025, 15(9), 947; https://doi.org/10.3390/brainsci15090947 - 29 Aug 2025
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Abstract
Background/Objectives: Sequence learning, the ability to pick up on regularities in our environment to facilitate behavior, is critically dependent on striatal structures in the brain, with the putamen emerging as a critical hub for implicit sequence learning. As the putamen is known to [...] Read more.
Background/Objectives: Sequence learning, the ability to pick up on regularities in our environment to facilitate behavior, is critically dependent on striatal structures in the brain, with the putamen emerging as a critical hub for implicit sequence learning. As the putamen is known to shrink with age, and age-related declines in sequence learning abilities are common, it has been hypothesized that the structural integrity of the putamen is likely related to sequence learning outcomes. However, the structural literature is sparse. One reason may be that traditional structural imaging measures, like volume, are not sufficiently sensitive to measure changes that are related to performance outcomes. We propose that magnetic resonance elastography (MRE), an emerging neuroimaging tool that provides quantitative measures of microstructural integrity, may fill this gap. Methods: In this study, both sequence learning abilities and the structural integrity of the putamen were assessed in 61 cognitively healthy middle-aged and older adults (range: 45–78 years old). Sequence learning was measured via performance on the Serial Reaction Time Task. Putamen integrity was assessed in two ways: first, via standard structural volume assessments, and second, via MRE measures of tissue integrity. Results: Age significantly correlated with both putamen volume and stiffness but not sequence learning scores. While sequence learning scores did not correlate with volume, MRE-derived measures of putamen stiffness were significantly correlated with learning outcomes such that individuals with stiffer putamen showed higher learning scores. A series of control analyses were performed to highlight the specificity and sensitivity of this putamen stiffness–sequence learning relationship. Conclusions: Together these data indicate that microstructural changes that occur in the putamen as we age may contribute to changes in sequence learning outcomes. Full article
(This article belongs to the Special Issue Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease)
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17 pages, 1098 KB  
Article
Attentional Functioning in Healthy Older Adults and aMCI Patients: Results from the Attention Network Test with a Focus on Sex Differences
by Laura Facci, Laura Sandrini and Gabriella Bottini
Brain Sci. 2025, 15(7), 770; https://doi.org/10.3390/brainsci15070770 - 19 Jul 2025
Viewed by 510
Abstract
Background/Objectives: The prognostic uncertainty of Mild Cognitive Impairment (MCI) imposes comprehensive neuropsychological evaluations beyond mere memory assessment. However, previous investigations into other cognitive domains, such as attention, have yielded divergent findings. Furthermore, while evidence suggests the presence of sex differences across the [...] Read more.
Background/Objectives: The prognostic uncertainty of Mild Cognitive Impairment (MCI) imposes comprehensive neuropsychological evaluations beyond mere memory assessment. However, previous investigations into other cognitive domains, such as attention, have yielded divergent findings. Furthermore, while evidence suggests the presence of sex differences across the spectrum of dementia-related conditions, no study has systematically explored attentional disparities between genders within this context. The current study aims to investigate differences in the attentional subcomponents, i.e., alerting, orienting, and executive control, between patients with MCI and healthy older controls (HOCs), emphasizing interactions between biological sex and cognitive impairment. Methods: Thirty-six participants (18 MCI, and 18 HOCs) were evaluated using the Attention Network Test (ANT). Raw RTs as well as RTs corrected for general slowing were analyzed using Generalized Mixed Models. Results: Both health status and sex influenced ANT performance, when considering raw RTs. Nevertheless, after adjusting for the baseline processing speed, the effect of cognitive impairment was no longer evident in men, while it persisted in women, suggesting specific vulnerabilities in females not attributable to general slowing nor to the MCI diagnosis. Moreover, women appeared significantly slower and less accurate when dealing with conflicting information. Orienting and alerting did not differ between groups. Conclusions: To the best of our knowledge, this is the first study investigating sex differences in attentional subcomponents in the aging population. Our results suggest that previously reported inconsistencies about the decline of attentional subcomponents may be attributable to such diversities. Systematically addressing sex differences in cognitive decline appears pivotal for informing the development of precision medicine approaches. Full article
(This article belongs to the Special Issue Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease)
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