Introduction Cognitive rehabilitation (CR) enhances the autonomy of patients with Alzheimer’s disease. Their daily activities are likely dependent on attention networks. Method This pilot resting-state fMRI study investigated the cerebral correlates of CR in participants with mild Alzheimer disease (n = 22), compared to a control intervention in patients (n = 21) and in healthy participants (n = 27). Connectivity changes between dorsal and ventral attention networks were expected after 3 months of rehabilitation. Results A mixed ANOVA comparing pre- and post-intervention data across groups revealed increased connectivity between the dorsal and the ventral attention network following CR (FDR-corrected P = .0072). A post hoc correlation analysis of post-intervention data in the CR group showed that greater autonomy in daily activities was associated with stronger functional relationship between the two attention networks (FDR-corrected P = .0001). Conclusion Enhanced connectivity between attention networks may be a characteristic of CR benefits in individuals with mild Alzheimer disease.

Abstract Purpose Brain ageing involves interrelated changes in molecular processes, neuroinflammatory mechanisms, brain macro- and microstructure, sleep physiology, and cognition. The 50 to 70 years age range represents a critical transition period, in which these subtle alterations may precede measurable cognitive decline and the onset of clinical neurodegenerative disease. To allow systematic investigation of these early alterations and the subsequent progression in brain aging, we provide an open-access data resource from a multidisciplinary longitudinal study integrating neuroimaging, genetics, sleep, and neuropsychological phenotyping with assessments at baseline and at 2-year follow-up. Acquisition and Validation Methods The baseline cohort comprises 101 community-dwelling participants (50-69 years old) who underwent magnetic resonance imaging (MRI) using a 3T protocol that included high-resolution structural imaging (T1- and T2-weighted), quantitative multi-parametric acquisitions with B1 mapping, and multi-shell diffusion-weighted imaging. Moreover, positron emission tomography (PET) imaging was performed using [18F]Flutemetamol or [18F]Florbetapir (amyloid- β tracers) in all participants, with a subset also undergoing [18F]THK-5351 PET (tau-related/neuroinflammation). The dataset was complemented by extensive phenotypic data, including sleep and neuropsychological assessments, and by genotype data through genome-wide analysis. 66 participants underwent a 2-year cognitive follow-up, enabling longitudinal analyses of cognitive trajectories. Data acquisition and curation were performed using standardized procedures, with systematic quality control to support reliable cross-sectional and longitudinal analyses. Data Format and Usage Notes All data are distributed in a BIDS-compliant format, and released in open-access (EBRAINS). Potential Applications This dataset supports multimodal analyses, allowing the identification of interpretable patterns characterizing brain ageing from multiple perspectives. It enables the comparison of different models to derive (semi)quantitative MRI parameters, the discovery of imaging biomarkers associated with early cognitive decline, and the monitoring or prediction of brain ageing progression. In addition, it offers focused coverage of adults aged 50–70 years, which is often underrepresented in existing healthy subjects public datasets. Key Points COFITAGE is a deeply phenotyped, longitudinal, multimodal dataset of 101 healthy late middle-aged adults (50-70 years). The COFITAGE dataset combines PET, MRI, sleep phenotyping, genotyping, and extensive neuropsychological assessment. The dataset supports diverse applications, from preclinical AD biomarker studies to investigations of hippocampal vulnerability, amyloid-tau-metabolism interactions, sleep-dependent modulation of molecular pathology, and multimodal predictive modeling of cognitive trajectories.

BACKGROUND:The recent approval of disease-modifying therapies (DMTs) for early Alzheimer's disease (AD) marks a major shift in clinical practice. Biomarker confirmation of amyloid pathology is now required alongside clinical assessment, and blood-based tests are improving accessibility. This creates increased demand for timely and accurate diagnosis while avoiding overdiagnosis in low-probability cases. This Belgian consensus aims to guide biomarker-based diagnosis of AD in the era of DMTs and to highlight the system adaptations required for safe and equitable implementation. Belgium, with universal healthcare but regionally organised dementia care, provides a relevant case to illustrate both opportunities and challenges. METHODS:This consensus was developed by 31 experts in cognitive neurology, geriatrics, neuropsychology, neuroimaging, neurochemistry, and primary care, coordinated by the Belgian Dementia Council (BeDeCo). Recommendations were based on multidisciplinary discussion, current evidence, and the organisation of dementia care in Belgium. RESULTS:The consensus outlines a stepwise diagnostic approach that integrates clinical assessment with biomarker confirmation using cerebrospinal fluid, amyloid-PET, and emerging blood-based tests. We review the strengths and limitations of each modality and provide guidance for use across clinical scenarios. Using Belgium as a case example, we illustrate challenges that are shared across European healthcare systems, such as limited reimbursement, unequal access to expertise, and insufficient diagnostic capacity, and formulate pragmatic recommendations to address these issues. CONCLUSIONS:This consensus offers practical guidance for embedding biomarker-based diagnostic strategies into clinical care. By outlining structured pathways and system-level priorities, it facilitates safe, feasible, and equitable implementation of DMTs for AD.

Patients with Alzheimer’s disease (AD) are less accurate than controls to predict their episodic performance, but they are as accurate as controls to predict their semantic performance. However, the dissociation between episodic and semantic metamemory had never been tested directly in the same patients. This study aimed to explore the dissociation between episodic and semantic metamemory in AD using the feeling-of-knowing paradigm. In addition, we investigated the link between memory awareness and resting-state cerebral glucose metabolism and gray matter density, in episodic and semantic tasks independently. Data from 50 patients with AD were compared to data from 30 healthy controls. Results showed that patients with AD had more difficulties to predict their recognition in the episodic task than in the semantic task, while this difference was smaller in controls. However, this dissociation was only shown with a measure of absolute accuracy, but not with a measure of relative accuracy. Lack of awareness in the episodic task was associated with hypometabolism in right frontoparietal areas in patients with AD, while semantic metamemory was associated with gray matter integrity in the left angular gyrus. The consequence of metacognitive bias and memory status on metamemory judgments are discussed.

With aging, slight changes in some cognitive processes can be observed. Therefore, we aimed to assess if meditation expertise is associated with preserved cognition in key domains affected in aging. We used data from two older-adult samples of the Medit-Ageing Age-well Study: 135 non-meditators and 27 expert meditators. We examined group differences in four objective cognitive domains (attention, executive functioning, episodic memory, and global cognition) and three subjective scores: Cognitive Difficulties Scale (CDS) total score as well as Attentional Style Questionnaire (ASQ) internal and external scores using generalized mixed effect models, controlling for age, sex, and education. We did not observe group differences on attentional, executive and global cognitive scores or on ASQ internal score and CDS total score. However, meditators reported less external distraction (ASQ external score) and had better memory than non-meditators. These cross-sectional results indicate a better management of external stimuli and higher memory performance in expert meditators. Memory difficulties and distractions being the main complaints of older people, prolonged meditation practice could lead them to greater cognitive capacities important for healthy aging.Trial registration: NCT02977819 (ClinicalTrials.gov).

In recent years, there has been a growing interest in individual differences in autobiographical memory. The ability to recall details from personal past events correlates with the volume of specific hippocampal subfields in healthy adults. Although the posterior hippocampus is believed to process detailed memory representations independently of the memory's age, little is known about individual differences in the ability to recall newly encoded events in detail, and how these differences relate to hippocampal subregions. In this preregistered study, we scored the story recalls from 89 healthy middle-aged participants with a newly designed method that allows to distinguish information recalled in detail from gist recall (i.e., when only the general idea is recalled). After a 20-min delay, detailed information was transformed into gists, which is in line with recent evidence that gists can emerge rapidly after a new experience. In addition, we segmented the anterior and posterior hippocampal subfields CA1, CA2/3, dentate gyrus, and subiculum from highresolution structural MRI. As predicted, the volume of the posterior hippocampus was positively correlated with the detail score but not with the gist score, yet this effect was significant in the right hemisphere only. We also observed trends towards associations between the detail score and specific subfields of the right posterior hippocampus, but none survived statistical correction for multiple comparisons. Finally, we found no evidence for the expected age-related increase in the use of gists over details. Taken together, these results suggest that the posterior hippocampus supports detail memory in the recall of both remote and newly acquired memories. (c) 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cognitive function alterations are a feature of the cognitive aging process. Additionally, aging is marked by macro- and micro-structural changes in the brain, such as gray matter (GM) atrophy, iron accumulation, and demyelination. This study explores the association between cognitive function and cooccurrence of brain micro- and macro-structural changes in healthy older adults. One hundred and one participants (32% men, age range: 50-69 years) were included in this study. All participants completed a cognitive assessment resulting in composite scores with mean = 0.00, s.d. = 0.99 for attention, executive functions, and memory. The preclinical Alzheimer’s cognitive composite (PACC5) was calculated for all participants (mean = 0.00, s.d. = 2.99). Quantitative magnetic resonance imaging (MRI) data were obtained using multiparametric mapping protocol. The association between cognitive composite scores and combinations of tissue properties was tested using multivariate generalized linear models (GLM) in Statistical Parametric Mapping (SPM) software. Voxel-wise multivariate GLM analyses revealed significant associations after family-wise error rate correction between executive functions and the combination of macro- and micro-structural changes within the cerebellum including right crus I and II, VII-b (see Figure 1-A). As illustrated in Figure 1, panels B and C, we also detected a correlation between memory and combined microstructural alterations in the in the left Cerebellum VIII-b, as well as bilaterally within the cingulate gyrus and insula. These findings highlight the role of the cerebellum in cognition besides the complex relationship between cognition and brain micro- and macro-structural properties in aging. As such, the involvement of the cerebellum in motor coordination and procedural memory may potentially influence executive functions

Event-based modeling (EBM) traces sequential progression of events in complex processes like neurodegenerative diseases, adept at handling uncertainties. This study validated an EBM for Alzheimer’s disease (AD) staging designed by EuroPOND, an EU-funded Horizon 2020 project, using research and real-world datasets, a crucial step towards application in multi-center trials. The training dataset comprised 1737 subjects from ADNI-1/GO/2, using the EuroPOND EBM toolbox. Testing datasets included a research cohort from University of Antwerp (controls, CN (n = 46), subjective cognitive decline, SCD (n = 10), mild cognitive impairment, MCI (n = 47), AD dementia, ADD (n = 16)) and a real-world cohort from 9 Belgian Dementia Council memory clinics (CN (n = 91), SCD (n = 66), (non-amnestic) naMCI (n = 54), aMCI (n = 255), and ADD (n = 220). Biomarkers included: 2 clinical scores (Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT)); 3 CSF-biomarkers (Aβ1−42, P-tau181, total-Tau); and 4 magnetic resonance imaging (MRI) biomarkers (volumes of the hippocampi, temporal, parietal, and frontal cortices) computed with icobrain dm. The naMCI and aMCI groups were compared by EBM stage proportions, and the model’s effectiveness at patient level was evaluated. The research cohort’s maximum likelihood event sequence comprised CSF Aβ1-42, P-tau181, T-tau, RAVLT, MMSE, and cortical volumes. The clinical cohort’s order was frontal cortex volume, MMSE, and remaining cortical regions. aMCI subjects showed higher staging than naMCI, with 54

Aging is associated with cognitive changes, even in the absence of brain pathology. This study aimed to determine if meditation training, by comparison to active and passive control groups, is linked to changes in the perception of cognitive functioning in older adults. One hundred thirty-four healthy older participants from the Age-Well Randomized Clinical Trial were included: 45 followed a meditation training, 45 a non-native language training and 44 had no intervention. Subjective cognition was assessed at baseline and following the 18-month intervention period. Perception of attentional efficiency was assessed using internal and external Attentional Style Questionnaire (ASQ) subscale scores. Perception of global cognitive capacities was measured via the total score of Cognitive Difficulties Scale (CDS). Deltas ([posttest minus pretest scores]/standard deviation at pretest) were calculated for the analyses. Generalized mixed effects models controlling for age, sex, education and baseline scores revealed that meditation training decreased the vulnerability score toward external distractors measured by the ASQ compared to non-native language training. However, no between-groups differences on ASQ internal or CDS total scores were observed. Results suggest a beneficial effect of meditation practice on perceived management of external distracting information in daily life. Meditation training may cultivate the ability to focus on specific information (e.g., breath) and ignore stimulation from other kinds of stimuli (e.g., noise).

Medical imaging technologies have undergone extensive development, enabling non-invasive visualization of clinical information. The traditional review of medical images by clinicians remains subjective, time-consuming, and prone to human error. With the recent availability of medical imaging data, quantification have become important goals in the field. Radiomics, a methodology aimed at extracting quantitative information from imaging data, has emerged as a promising approach to uncover hidden biological information and support decision-making in clinical practice. This paper presents a review of the radiomic pipeline from the clinical neuroimaging perspective, providing a detailed overview of each step with practical advice. It discusses the application of handcrafted and deep radiomics in neuroimaging, stratified by neurological diagnosis. Although radiomics shows great potential for increasing diagnostic precision and improving treatment quality in neurology, several limitations hinder its clinical implementation. Addressing these challenges requires collaborative efforts, advancements in image harmonization methods, and the establishment of reproducible and standardized pipelines with transparent reporting. By overcoming these obstacles, radiomics can significantly impact clinical neurology and enhance patient care.

The regional integrity of brain subcortical structures has been implicated in sleep-wake regulation, however, their associations with sleep parameters remain largely unexplored. Here, we assessed association between quantitative Magnetic Resonance Imaging (qMRI)-derived marker of the myelin content of the brainstem and the variability in the sleep electrophysiology in a large sample of 18-to-31 years healthy young men (N = 321; similar to 22 years). Separate Generalized Additive Model for Location, Scale and Shape (GAMLSS) revealed that sleep onset latency and slow wave energy were significantly associated with MTsat estimates in the brainstem (p(corrected) <= 0.03), with overall higher MTsat value associated with values reflecting better sleep quality. The association changed with age, however (MTsat-by-age interaction-p(corrected) <= 0.03), with higher MTsat value linked to better values in the two sleep metrics in the younger individuals of our sample aged similar to 18 to 20 years. Similar associations were detected across different parts of the brainstem (p(corrected) <= 0.03), suggesting that the overall maturation and integrity of the brainstem was associated with both sleep metrics. Our results suggest that myelination of the brainstem nuclei essential to regulation of sleep is associated with inter-individual differences in sleep characteristics during early adulthood. They may have implications for sleep disorders or neurological diseases related to myelin.

INTRODUCTION:Awareness influences the evolution of neurodegenerative dementias. We gathered participants' and caregivers assessments of dependence in daily activities and we studied how each score would be related to next year participant autonomy, independently of other explicative variables.METHOD:We retrospectively analyzed data from mildly demented participants with a clinical diagnosis of Alzheimer's disease (AD, n = 186) and frontotemporal dementia (FTD, n = 29) and their relatives. A research tool was used to assess participant dependence in 98 daily activities and associated caregiver burden. A discrepancy score between the patient's and relative's judgment was calculated to evaluate awareness of dependence in activities at baseline. This dependence scores, as well as sex, age, education, and 1 year difference in Mini-Mental State Examination were taken as possible explicative variables for dependence in activities adapted by therapists during a 1-year cognitive rehabilitation program.RESULTS:Patients with FTD showed less awareness for daily dependence (discrepancy 20.9% vs. 11.8% in AD). Both groups benefited from cognitive rehabilitation (25% decrease in dependence) and subjective burden of relatives was decreased in both groups. In the AD group, there was a significant positive relationship between both caregiver (P < 0.001) and participant's (P < 0.02) evaluation of dependence in daily activities at inclusion and dependence of participants in adapted activities after 1 year.DISCUSSION:Awareness of impairment in daily activities is a clinical symptom that is more important at inclusion in FTD than in AD. However, in participants with AD who, as a group, significantly benefit from a cognitive rehabilitation program, not only caregiver's but also participant's assessment of dependence at baseline is correlated to subsequent, next year greater dependence in daily activities adapted by the therapists. Although discrepant, both caregiver and participant evaluations appear to be important variables to understand the evolution and the benefit of care in participants at early stages of dementia.

Background: Abnormal tau accumulation is first observed in several neuromodulatory subcortical nuclei before its emergence in the allocortex, and long before the first deposits of amyloid-beta (A beta) plaques. Crucially, the posterior hypothalamus has been put forward as a critical site for Alzheimer's disease (AD) pathogenesis but its role in AD-related processes remains poorly investigated in humans. Here, we aimed to investigate whether the structural integrity of the posterior hypothalamus, as assessed in vivo, is associated with PET-measured AD pathology and cognitive performance in cognitively unimpaired (CU) and impaired older individuals. Methods: 151 CU individuals, 75 mild cognitive impairment (MCI) and 35 AD patients (mean +/- SD age = 76.6 +/- 6.7y., 137 women; Table 1) from the ADNI3 dataset were included. The volume of the posterior hypothalamus (corrected for intracranial volume) was derived from structural T1-weighted images using a deep convolutional network algorithm (Figure 1a). ([18F])Flortaucipir-PET was used to measure tau burden in the entorhinal cortex (standardized uptake volume ratio [SUVR], partial volume corrected values). Amyloid-beta (A beta) positivity was determined with ([18F])Florbetaben- or ([18F])Florbetapir-PET in a cortical summary region (SUVR values). Cognition was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). Analyses were adjusted for age, sex, and education. Results: AD patients exhibited lower posterior hypothalamic volume compared to CU A beta- (p = 0.003) and CU A beta+ participants (p = 0.01) but no significant difference was observed between CU and MCI patients nor between MCI and AD patients (Figure 1b). Linear regression models revealed that lower posterior hypothalamic volume was associated with higher entorhinal tau-PET values (p = 0.02, Figure 2a). In addition, CU A beta+ with higher posterior hypothalamic volume exhibited higher entorhinal tau-PET values compared to a negative slope in CU A beta- participants (p = 0.05, Figure 2b). Finally, lower posterior hypothalamic volume was related to lower PACC scores (p<0.001, Figure 2c), which was mainly driven by AD patients (p<0.05 for comparisons with CU and MCI, Figure 2d). Conclusions: Our findings indicate that the posterior hypothalamus is linked to disease-related pathophysiological and cognitive changes. Future analyses will explore whether posterior hypothalamic volume is associated with inflammatory markers and changes in tau accumulation and cognitive performance over time.

Abstract Objectives This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject. Results MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p < .001) and BPAD (r = -0.26,p < .001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p = .014) and moderate (p = .040) drinkers. Conclusions Brain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health.

18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) is a useful paraclinical exam for the diagnosis of Alzheimer's disease (AD). In this narrative review, we report seminal studies in clinically probable AD that have shown the importance of posterior brain metabolic decrease and the paradoxical variability of the hippocampal metabolism. The FDG-PET pattern was a sensitive indicator of AD in pathologically confirmed cases and it was used for differential diagnosis of dementia conditions. In prodromal AD, the AD FDG-PET pattern was observed in converters and predicted conversion. Automated data analysis techniques provided variable accuracy according to the reported indices and machine learning methods showed variable reliability of results. FDG-PET could confirm AD clinical heterogeneity and image data driven analyses identified hypometabolic subtypes with variable involvement of the hippocampus, reminiscent if the paradoxical FDG uptake. In studies dedicated to clinical and metabolic correlations, episodic memory was related to metabolism in the default mode network (and Papez's circuit) in prodromal and mild AD stages, and specific cognitive processes were associated to precisely distributed brain metabolism. Cerebral metabolic correlates of anosognosia could also be related to current neuropsychological models. AD FDG-PET pattern was reported in preclinical AD stages and related to cognition or to conversion to mild cognitive impairment (MCI). Using other biomarkers, the AD FDG-PET pattern was confirmed in AD participants with positive PET-amyloid. Intriguing observations reported increased metabolism related to brain amyloid and/or tau deposition. Preserved glucose metabolism sometimes appear as a compensation, but it was frequently detrimental and the nature of such a preservation of glucose metabolism remains an open question. Limbic metabolic involvement was frequently related to non-AD biomarkers profile and clinical stability, and it was reported in non-AD pathologies, such as the limbic predominant age-related encephalopathy (LATE). FDG-PET abnormalities observed in the absence of classical AD proteinopathies can be useful to search for pathological mechanisms and differential diagnosis of AD.

Non-pharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. We investigated the effects of 18-months meditation or non-native language training versus no intervention on cognition in older adults. Age-Well was an observer-blind, randomised, controlled clinical trial with three parallel arms. Cognitively healthy adults aged ≥ 65 years and were recruited in France. Participants were randomised (1:1:1) to a meditation training, non-native language (English) training, or a no intervention group for 18 months. Cognition (a pre-specified secondary outcome) was assessed pre- and post-intervention via the Preclinical Alzheimer’s Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. Linear mixed models, adjusted for age, sex, and education, evaluated cognitive changes between arms. Baseline neocortical amyloid deposition was added as a fixed effect in a sensitivity analysis. Additional sensitivity analyses assessed intervention effects for participants who attended at least 20% of intervention classes or were classified as ‘responders’. 137 participants were randomly assigned to meditation training (n = 45), non-native language training (n = 46), or no intervention (n = 46). Two participants were excluded for not meeting eligibility criteria, and one died during follow-up (Figure 1). A positive effect of non-native language training was observed on episodic memory relative to the no intervention group (0·32 [95% CI: 0·04-0·61], p = 0·025), and on PACC5 scores compared to meditation training (0·33 [95% CI: 0·01-0·66], p = 0·045; Figure 2). In sensitivity analyses, neither the inclusion of amyloid as an additional covariate nor the exclusion of participants who attended <20% of intervention classes affected results. Following exclusion of ‘non-responders’, evidence for beneficial effects (relative to the no intervention group) on episodic memory became significant for meditation training (0·33 [0·01, 0·66]), and was weakened for non-native language training (0·30 [-0·02, 0·62]). No other between-group differences emerged. Among cognitively healthy older adults, there was limited evidence for positive effects of 18-months meditation training on cognition. However, in addition to having real-life utility, non-native language learning in late life may have beneficial effects on cognitive domains affected early in Alzheimer’s disease. Studies investigating whether these effects are long-lasting are warranted.

BACKGROUND:The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described.OBJECTIVE:This systematic review aimed to gather the current understanding of the pathophysiological mechanisms linking periodontitis to AD.METHODS:An electronic systematic search of the PubMed/MEDLINE, Scopus, and Embase databases was performed using the following PECO question: How can periodontitis or periodontal bacteria influence Alzheimer's disease features?". Only preclinical studies exploring the biological links between periodontitis and AD pathology were included. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and the Syrcle and Camarades protocols were used to assess the risk of bias.RESULTS:After a systematic screening of titles and abstracts (n = 3,307), thirty-six titles were selected for abstract reading, of which 13 were excluded (k = 1), resulting in the inclusion of 23 articles. Oral or systemic exposure to periodontopathogens or their byproducts is responsible for both in situ brain manifestations and systemic effects. Significant elevated rates of cytokines and amyloid peptides (Aβ) and derivate products were found in both serum and brain. Additionally, in infected animals, hyperphosphorylation of tau protein, hippocampal microgliosis, and neuronal death were observed. Exposure to periodontal infection negatively impairs cognitive behavior, leading to memory decline.CONCLUSIONS:Systemic inflammation and brain metastatic infections induced by periodontal pathogens contribute to neuroinflammation, amyloidosis, and tau phosphorylation, leading to brain damage and subsequent cognitive impairment.