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Brain Sciences
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Advances in Memory and Cognitive Decline Associated with Aging and...
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Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurodegenerative Diseases".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 9949

Special Issue Editor

Dr. Pavan Kumar

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Guest Editor
Department of Anatomy and Cell Biology, College of Medicine, The University of Illinois at Chicago, Chicago, IL, USA
Interests: Alzheimer's disease; memory; neurogenesis; aging; neurodegeneration; neuroinflammation; cognition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer's disease (AD) is characterized by progressive memory impairments. Deficits in hippocampal neurogenesis, altered neuroinflammatory events, Tau pathology, loss of neuronal connection, and vascular senescence have been observed in human patients as well as in mouse models of familial Alzheimer's disease (FAD). 

Understanding the role of different risk factors associated with AD pathology is still warranted. Recent advancements in the scientific community are empowering us to reach milestones each day. Tracing the engram ensemble through calcium imaging and manipulating it through optogenetics/chemogenetics in freely moving animals during different behavioral tasks enable us to understand how AD pathology affects cognition. In addition, techniques such as spatial transcriptomics give us in-depth information on how gene profiles change in each cell in a healthy vs. AD brain. We invite the scientific community to participate in our Special Issue, "Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease", in order to share their valuable research and ideas. 

Dr. Pavan Kumar
Guest Editor

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Keywords

  • neurodegeneration
  • neuroprotection
  • neurogenesis
  • learning and memory
  • engram
  • neuro-vascular

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Published Papers (7 papers)

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Research

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10 pages, 1434 KiB  
Article
Geographic Distribution and Future Projections of Mild Cognitive Impairment and Dementia in Greece: Analysis from 1991 to 2050
by Themis P. Exarchos, Konstantina Skolariki, Vasiliki Mahairaki, Constantine G. Lyketsos, Panagiotis Vlamos, Nikolaos Scarmeas, Efthimios Dardiotis and on behalf of the Hellenic Initiative Against Alzheimer’s Disease (HIAAD)
Brain Sci. 2025, 15(6), 661; https://doi.org/10.3390/brainsci15060661 - 19 Jun 2025
Viewed by 386
Abstract
Background: Greece is among the fastest-aging countries globally, with one of the highest proportions of elderly individuals. As a result, the prevalence of mild cognitive impairment (MCI) and dementia is among the highest in Europe. The distribution of affected individuals varies considerably across [...] Read more.
Background: Greece is among the fastest-aging countries globally, with one of the highest proportions of elderly individuals. As a result, the prevalence of mild cognitive impairment (MCI) and dementia is among the highest in Europe. The distribution of affected individuals varies considerably across different regions of the country. Method: We estimated the number of people living with MCI or dementia in Greece and visualized these estimates using heatmaps by regions for four census years: 1991, 2001, 2011, and 2023 (the 2023 census was delayed due to the COVID-19 pandemic). Age- and sex-specific prevalence rates of MCI and dementia were obtained from the Hellenic Longitudinal Investigation of Aging and Diet. These prevalence rates were then applied to population data from each census to estimate the number of affected individuals per region. Results: There was a consistent increase in the number of people living with MCI, rising from 177,898 in 1991 to 311,189 in 2023. Dementia cases increased from 103,535 in 1991 to 206,939 in 2023. Projections based on future census data for 2035 and 2050 suggest that the number of people with MCI will reach 375,000 and 440,000, respectively, while dementia cases will increase to 250,000 in 2035 and 310,000 in 2050. Conclusion: Given that each person with dementia typically requires care from at least two caregivers over time, these projections highlight the profound impact the dementia epidemic will have on Greece. The heatmaps developed in this study can serve as valuable tools for policymakers in designing and implementing clinical care programs tailored to the needs of each region based on the projected burden of disease. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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16 pages, 3021 KiB  
Article
Prediction of Alzheimer’s Disease Based on Multi-Modal Domain Adaptation
by Binbin Fu, Changsong Shen, Shuzu Liao, Fangxiang Wu and Bo Liao
Brain Sci. 2025, 15(6), 618; https://doi.org/10.3390/brainsci15060618 - 7 Jun 2025
Viewed by 496
Abstract
Background/Objectives: Structural magnetic resonance imaging (MRI) and 18-fluoro-deoxy-glucose positron emission tomography (PET) reveal the structural and functional information of the brain from different dimensions, demonstrating considerable clinical and practical value in the computer-aided diagnosis of Alzheimer’s disease (AD). However, the structure and semantics [...] Read more.
Background/Objectives: Structural magnetic resonance imaging (MRI) and 18-fluoro-deoxy-glucose positron emission tomography (PET) reveal the structural and functional information of the brain from different dimensions, demonstrating considerable clinical and practical value in the computer-aided diagnosis of Alzheimer’s disease (AD). However, the structure and semantics of different modal data are different, and the distribution between different datasets is prone to the problem of domain shift. Most of the existing methods start from the single-modal data and assume that different datasets meet the same distribution, but they fail to fully consider the complementary information between the multi-modal data and fail to effectively solve the problem of domain distribution difference. Methods: In this study, we propose a multi-modal deep domain adaptation (MM-DDA) model that integrates MRI and PET modal data, which aims to maximize the utilization of the complementarity of the multi-modal data and narrow the differences in domain distribution to boost the accuracy of AD classification. Specifically, MM-DDA comprises three primary modules: (1) the feature encoding module, which employs convolutional neural networks (CNNs) to capture detailed and abstract feature representations from MRI and PET images; (2) the multi-head attention feature fusion module, which is used to fuse MRI and PET features, that is, to capture rich semantic information between modes from multiple angles by dynamically adjusting weights, so as to achieve more flexible and efficient feature fusion; and (3) the domain transfer module, which reduces the distributional discrepancies between the source and target domains by employing adversarial learning training. Results: We selected 639 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and considered two transfer learning settings. In ADNI1→ADNI2, the accuracies of the four experimental groups, AD vs. CN, pMCI vs. sMCI, AD vs. MCI, and MCI vs. CN, reached 92.40%, 81.81%, 81.13%, and 85.45%, respectively. In ADNI2→ADNI1, the accuracies of the four experimental groups, AD vs. CN, pMCI vs. sMCI, AD vs. MCI, and MCI vs. CN, reached 94.73%, 81.48%, 85.48%, and 81.69%, respectively. Conclusions: MM-DDA is compared with other deep learning methods on two kinds of transfer learning, and the performance comparison results confirmed the superiority of the proposed method in AD prediction tasks. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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14 pages, 656 KiB  
Article
The Contribution of the Face-Name Associative Recognition Test to Objectifying the Impairment of Associative Memory in Subjective Cognitive Decline
by Joël Macoir, Pascale Tremblay and Carol Hudon
Brain Sci. 2024, 14(11), 1129; https://doi.org/10.3390/brainsci14111129 - 8 Nov 2024
Viewed by 1402
Abstract
Objective: Subjective cognitive decline (SCD) is defined as a self-reported perception of cognitive decline that occurs without clear objective signs of cognitive impairment. There is still uncertainty in the literature about the reliability of SCD as an accurate indicator of the early stages [...] Read more.
Objective: Subjective cognitive decline (SCD) is defined as a self-reported perception of cognitive decline that occurs without clear objective signs of cognitive impairment. There is still uncertainty in the literature about the reliability of SCD as an accurate indicator of the early stages of major neurocognitive disorders. Furthermore, objectifying cognitive impairment in SCD is difficult, mainly due to the insensitivity of the assessment instruments. The main objective of this study was to investigate the potential contribution of the face-name associative recognition test (FNART) to the objective identification of memory impairment in SCD. Method: A research sample of 69 adults with SCD and 69 healthy controls (HCs) recruited in the community were administered in the FNART, which included 32 photographs of neutral faces associated with 32 first names. Results: The total score of the HC group in the FNART was significantly better than that of the SCD group. Moreover, analyses based on the serial position of the stimuli showed that the SCD group performed significantly worse than the HC group only for the middle items (stimuli placed at the beginning or end of learning lists are more likely to be recalled than those presented in the middle), while no primacy and recency effects were found in the HCs. Conclusions: These findings indicate that associative episodic memory is more vulnerable in individuals with subjective cognitive decline (SCD) compared to those without cognitive complaints. Additionally, they suggest that the FNART may be effective in identifying cognitive decline in the preclinical stage of Alzheimer’s disease. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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Review

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22 pages, 1278 KiB  
Review
Murine Non-Transgenic Models of Alzheimer’s Disease Pathology: Focus on Risk Factors
by Maricarmen Hernández-Rodríguez, Juan Manuel Vega López, Martín Martínez-Rosas, María Inés Nicolás-Vázquez and Elvia Mera Jiménez
Brain Sci. 2025, 15(3), 322; https://doi.org/10.3390/brainsci15030322 - 19 Mar 2025
Viewed by 538
Abstract
Alzheimer’s disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The [...] Read more.
Alzheimer’s disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The key pathological features of AD include Aβ senile plaques, neurofibrillary tangles (NFTs), and the activation of neuroinflammatory pathways. Presently, investigations into AD and assessing potential treatments predominantly utilize Aβ transgenic models. Conversely, non-transgenic models may provide valuable insights into the multifaceted pathological states associated with AD. Thus, these models may serve as practical complementary tools for evaluating therapeutic and intervention strategies, since the primary AD risk factors are most frequently modeled. This review aims to critically assess the existing literature on AD non-transgenic models induced by streptozotocin, scopolamine, aging, mechanical stress, metals, and dietary patterns to enhance their application in AD research. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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13 pages, 1079 KiB  
Review
Photobiomodulation as a Potential Treatment for Alzheimer’s Disease: A Review Paper
by Miaomiao Wang, Deeba Dinarvand, Clement T. Y. Chan, Anatol Bragin and Lin Li
Brain Sci. 2024, 14(11), 1064; https://doi.org/10.3390/brainsci14111064 - 26 Oct 2024
Cited by 4 | Viewed by 4378
Abstract
Background: Alzheimer’s disease (AD), the most prevalent form of dementia, is a leading neurodegenerative disorder currently affecting approximately 55 million individuals globally, a number projected to escalate to 139 million by 2050. Despite extensive research spanning several decades, the cure for AD remains [...] Read more.
Background: Alzheimer’s disease (AD), the most prevalent form of dementia, is a leading neurodegenerative disorder currently affecting approximately 55 million individuals globally, a number projected to escalate to 139 million by 2050. Despite extensive research spanning several decades, the cure for AD remains at a developing stage. The only existing therapeutic options are limited to symptom management, and are often accompanied by adverse side effects. The pathological features of AD, including the accumulation of beta-amyloid plaques and tau protein tangles, result in progressive neuronal death, synaptic loss, and brain atrophy, leading to significant cognitive decline and a marked reduction in quality of life. Objective: In light of the shortcomings of existing pharmacological interventions, this review explores the potential of photobiomodulation (PBM) as a non-invasive therapeutic option for AD. PBM employs infrared light to facilitate cellular repair and regeneration, focusing on addressing the disease’s underlying biomechanical mechanisms. Method: This paper presents a comprehensive introduction to the mechanisms of PBM and an analysis of preclinical studies evaluating its impact on cellular health, cognitive function, and disease progression in AD.The review provides a comprehensive overview of the various wavelengths and application methods, evaluating their efficacy in mitigating AD-related symptoms. Conclusions: The findings underscore the significant potential of PBM as a safe and effective alternative treatment for Alzheimer’s disease, emphasizing the necessity for further research and clinical trials to establish its therapeutic efficacy conclusively. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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14 pages, 454 KiB  
Review
Tailoring Semantic Interventions for Older Adults: Task-Focused and Person-Centered Approaches
by Vasiliki Folia and Susana Silva
Brain Sci. 2024, 14(9), 907; https://doi.org/10.3390/brainsci14090907 - 7 Sep 2024
Viewed by 1434
Abstract
In this narrative review, we explore the latest evidence on semantic interventions for older adults, including both prevention and rehabilitation/remediation efforts, discussing them particularly in the context of dementia. Cognitive interventions vary in their level of structure, encompassing standardized (task-focused tasks) and unstandardized [...] Read more.
In this narrative review, we explore the latest evidence on semantic interventions for older adults, including both prevention and rehabilitation/remediation efforts, discussing them particularly in the context of dementia. Cognitive interventions vary in their level of structure, encompassing standardized (task-focused tasks) and unstandardized tasks (person-centered tasks). These interventions also differ in their target: rehabilitation or prevention. Addressing semantic knowledge/semantic memory/semantics is important, primarily because its efficiency impacts other cognitive domains. Semantic tasks are commonly included in preventive and rehabilitation programs, typically as standardized tasks with pre-defined semantic referents. On the other hand, person-centered approaches introduce personally relevant semantics, allowing patients to share thoughts and experiences with expressive language. Although these approaches offer benefits beyond cognitive improvement, their lack of structure may pose challenges. Our question club (CQ) program blends structured activities with personally relevant semantics, aiming to harness the advantages of both methods. Additionally, in this narrative review, we discuss future challenges and directions in the field of semantic interventions. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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Other

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9 pages, 2816 KiB  
Brief Report
White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function
by Rudolph Johnstone, Ida Rangus, Natalie Busby, Janina Wilmskoetter, Nicholas Riccardi, Sarah Newman-Norlund, Roger Newman-Norlund, Chris Rorden, Julius Fridriksson and Leonardo Bonilha
Brain Sci. 2025, 15(7), 692; https://doi.org/10.3390/brainsci15070692 - 27 Jun 2025
Viewed by 106
Abstract
Background: Type 2 diabetes is linked to impaired cognitive function, but the underlying mechanisms remain poorly understood. As white matter hyperintensities (WMHs) are common in diabetes and associated with vascular brain injury, we investigated whether WMH burden mediates the relationship between hemoglobin A1c [...] Read more.
Background: Type 2 diabetes is linked to impaired cognitive function, but the underlying mechanisms remain poorly understood. As white matter hyperintensities (WMHs) are common in diabetes and associated with vascular brain injury, we investigated whether WMH burden mediates the relationship between hemoglobin A1c (HbA1c) levels and cognition. Methods: We quantified WMH load using the Fazekas scale and conducted a mediation analysis with HbA1c as the independent variable, Fazekas scale as the mediator, and MoCA scores as the outcome variable. Results: WMHs partially mediated the relationship between HbA1c levels and MoCA scores (indirect effect = −0.224, 95% CI = −0.619 to −0.050, p = 0.001), accounting for approximately 15.6% of the total effect. Conclusions: This study suggests that WMHs partially mediate the association between chronically elevated blood glucose levels and cognitive impairment in neurologically healthy adults, supporting a potential microvascular mechanism in diabetes-related cognitive impairment. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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