Jul 2026· Movement Disorders· 1 citation· 28 references
Medicine
TL;DR
The results suggest that co-morbid AD pathology is not a major contributor to early cognitive changes in this sample of PD patients without dementia.
Abstract
Background
Alzheimer's disease (AD) co-pathology contributes to dementia in PD, but its role in earlier cognitive impairment remains uncertain.
Objective
To determine if p-tau217, a biomarker of early AD, is associated with cognitive impairment in PD.
Methods
Plasma p-tau217 levels in 167 PD patients without dementia and 63 controls were related to performance on standard neuropsychological testing, and to cognitive impairment as defined by a MoCA score <26 and by self-report. Plasma GFAP, NfL and APOE ε4 carrier status were also examined.
Results
No significant differences in p-tau217, GFAP and NfL level were observed between groups (pFDR > 0.08). Higher p-tau217 was associated with worse visuospatial function and greater self-reported cognitive impairment, but these associations did not survive correction (pFDR > 0.08). There was no association with cognitive impairment (pFDR > 0.08).
Abstract INTRODUCTION This study aimed to assess intra‐individual cognitive variability (IICV) in relation to Alzheimer's disease (AD) biomarkers. METHODS The National Alzheimer's Coordinating Center sample (n = 879), aged 50+ with a complete neuropsychological evaluation and AD biomarker data available (64% cognitively intact; 36% cognitively impaired). Moderated regression models using AD biomarkers, neurocognitive status, and interaction effects predicted IICV. AD biomarkers included cerebrospinal fluid (CSF) measures of Aβ1‐42, phosphorylated tau 181 (p‐Tau181), total tau (t‐Tau), and amyloid positron emission tomography. RESULTS Increased AD biomarker burden was associated with increased IICV among cognitively impaired individuals (correlational strength ranging from 0.149 to 0.460) but not among the cognitively intact group. DISCUSSION Increases in measures of amyloid, soluble tau, and neurodegeneration are associated with increased IICV among cognitively impaired older adults. The findings underscore the potential of IICV as a sensitive outcome measure. Future studies should replicate findings longitudinally and in more diverse samples.
S. S. Lin, Alicia L. Milam, Andrew Kiselica et al.· Alzheimer's & Dementia· 0 citations
Increased serum p-tau217 and decreased ApoE levels were significantly associated with greater AD severity, suggesting that both biomarkers may serve as complementary noninvasive indicators of disease severity in Alzheimer’s disease.
Ahmed Kadom Kalaf, Khawla A. Shemran, Waleed Azeez AlAmeedy· International Journal of Nut...· 0 citations
To examine associations between neurodegenerative and inflammatory biomarkers and motor function in adults with Alzheimer’s disease (AD), mild cognitive impairment (MCI), or at risk of AD. A systematic review was conducted using MEDLINE, Web of Science, Scopus, LILACS, and CENTRAL. Seventeen studies (2018–2026) were included. CSF Aβ42 levels were associated with gait speed, balance, and mobility outcomes, while p-tau, p-tau181, p-tau217, and t-tau correlated with mobility impairments, dual-task performance, and reduced physical function. Higher neurofilament light chain (NfL) levels were linked to poorer Short Physical Performance Battery (SPPB) performance, slower gait speed, and lower grip strength. One study found serum IL-8 associated with mobility outcomes. AD-related biomarkers, particularly Aβ42, p-tau, p-tau181, p-tau217, t-tau, and NfL, show consistent associations with gait disturbances, mobility decline, and reduced physical function. Motor changes may precede cognitive decline, supporting their potential as early indicators of neurodegeneration.
M. F. Serna, M. Mosquera, H. García-Perdomo· Neurological Sciences· 0 citations
Background Mild behavioral impairment (MBI), characterized by later-life emergence of persistent neuropsychiatric symptoms (NPS), is an early clinical indicator of dementia risk. Global MBI has been associated with Alzheimer's disease (AD) pathology; studies have also explored MBI domains. Prior work has linked MBI-apathy to AD cerebrospinal fluid (CSF) biomarkers, but whether associations are detectable using plasma-based biomarkers such as phosphorylated tau (p-tau) is unknown. Establishing such relationships is critical, as plasma biomarkers are more accessible than CSF. Objective To explore cross-sectional and longitudinal associations between MBI-apathy and plasma p-tau181 levels using Alzheimer's Disease Neuroimaging Initiative data. Methods Older adults with normal cognition or mild cognitive impairment were categorized as MBI-apathy (n = 69), non-MBI NPS (n = 112), and no-NPS (n = 215) based on Neuropsychiatric Inventory scores and symptom persistence over one year. Linear regression modelled cross-sectional associations between NPS group and plasma p-tau181, adjusting for age, sex, education, apolipoprotein E4 status, and Mini-Mental State Examination score. Hierarchical linear mixed-effects modelling assessed associations over two and three years, including time-by-NPS group interactions. Results MBI-apathy was associated with significantly higher plasma p-tau181 levels at baseline (24.05% [6.06–45.08%]; adjusted p = 0.014), and over two (26.46% [7.24–49.12%]; adjusted p = 0.012) and three years (29.28% [10.17–51.72%]; adjusted p = 0.004) compared to no-NPS. No significant associations were observed for non-MBI NPS. In sensitivity analyses, non-MBI apathy was not associated with plasma p-tau181 at baseline (−9.96% [−32.69–20.44%]; unadjusted p = 0.478). Conclusions MBI-apathy is associated with elevated plasma p-tau181 cross-sectionally and longitudinally, supporting MBI-apathy as a potential proxy marker of tau pathology for early AD detection.
Daniella Vellone, Rebeca Leon, Zahra Goodarzi et al.· Journal of Alzheimer's Disea...· 0 citations
Background Parkinson's disease (PD) patients may harbor coexisting Alzheimer's disease (AD) pathology that accelerates cognitive and motor decline. Defining biomarker-defined AD in PD is important for prognosis, patient counseling, and trial stratification. Objective To determine the prevalence of AD biomarker positivity in α-synuclein seed amplification assay (αSyn-SAA) positive PD and assess its impact on cognitive and motor progression. Methods We analyzed data from the Parkinson's Progression Markers Initiative, a multinational prospective cohort of de novo PD patients. Baseline CSF biomarkers included αSyn-SAA, amyloid-β1-42 (Aβ1-42), and phosphorylated tau181 (p-tau181). AD biomarker positivity was defined by a low Aβ1-42/high p-tau181 profile using the CSF Aβ1-42/p-tau181 ratio (<39.2). αSyn-SAA-positive PD participants with and without AD biomarker positivity were compared. Outcomes included cognition, Montreal Cognitive Assessment (MoCA), neuropsychological testing, and MDS-UPDRS motor scores over follow-up. Results Among 449 αSyn-SAA-positive PD patients, 42 (9.3%) met AD biomarker criteria (PD-AD). Baseline cognition and motor scores did not differ between PD-AD and PD without AD biomarkers (PD-nonAD). Over time, PD-AD patients showed greater cognitive decline, with lower MoCA scores and higher MCI prevalence at 5 years. At 8 years, PD-AD patients also demonstrated worse motor outcomes. MoCA <24 predicted AD biomarker positivity (PPV 15%; OR 6.1). APOE ε4 status was not associated with cognition. Conclusions Biomarker-defined AD identifies a distinct PD subgroup with accelerated cognitive and motor decline, independent of APOE ε4. A ratio-based CSF Aβ1-42/p-tau181 framework offers a practical approach to detect AD copathology in PD and refine prognostic stratification.
Daniel Zarhin, N. Bregman, T. Shiner et al.· Journal of Parkinson's Disea...· 0 citations
BackgroundGrowing evidence links cardiovascular health to Alzheimer's disease (AD). While elevated plasma homocysteine (Hcy) is associated with cognitive decline, the relationship between cerebrospinal fluid (CSF) Hcy and the core pathological biomarkers of AD remains unclear.ObjectiveThis study aimed to investigate the associations of CSF Hcy and plasma Hcy with CSF amyloid-β (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau).MethodsA total of 294 non-demented participants (110 cognitively normal, 184 with mild cognitive impairment) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were analyzed. Multivariate linear regression was used to analyze the relationships between CSF and plasma Hcy levels and CSF Aβ42, phosphorylated tau (p-tau), and total tau (t-tau). Logistic regression analyses assessed the association between Hcy levels and Aβ42 positivity, tau positivity, and neurodegeneration positivity.ResultsCSF Hcy levels showed significant positive associations with CSF p-tau and t-tau, as well as tau and neurodegeneration positivity. In contrast, no significant association was found between CSF Hcy and Aβ42 pathology. Notably, plasma Hcy was not associated with any AD-related biomarkers.ConclusionsCSF Hcy, rather than plasma Hcy, was associated with markers of tau pathology and neurodegeneration in non-demented older adults. These findings suggest that CSF Hcy may be more closely associated with tau-related pathological processes during the pre-dementia stages of AD. Further research is needed to explore the mechanisms underlying these associations.
Ji Hyung Lee, Geun Hui Won, Sang-Ick Lee et al.· Journal of Alzheimer's Disea...· 0 citations
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