Longitudinal assessment of the conversion of mild cognitive impairment into Alzheimer's dementia: Observations and mechanisms from neuropsychological testing and electrophysiology

Dunstan, D. M.; Barvas, E.; Guttmann, S.; Frusciante, R.; Viti, B.; Volpini, M.; Cannuccia, M.; Monaldini, C.; Tamagnini, F.; Goodfellow, M.; Tait, L.

doi:10.1101/2024.12.16.628666

bioRxiv · 10.1101/2024.12.16.628666

Longitudinal assessment of the conversion of mild cognitive impairment into Alzheimer's dementia: Observations and mechanisms from neuropsychological testing and electrophysiology

Dunstan, D. M.·Barvas, E.·Guttmann, S.·Frusciante, R.·Viti, B.·Volpini, M.·Cannuccia, M.·Monaldini, C.·Tamagnini, F.·Goodfellow, M.·Tait, L.

View original source ↗Export metadata ↓

Abstract

INTRODUCTIONElucidating and better understanding functional biomarkers of Alzheimers disease (AD) is crucial. By analysing a detailed longitudinal dataset, this study aimed to create a model-based toolset to characterise and understand the conversion of mild cognitive impairment (MCI) to AD. METHODSEEG, MRI, and neuropsychological data were collected from participants in San Marino: AD (n = 10), MCI (n = 20), and controls (n = 11). Across two additional years, MCI participants were classified as converters or non-converters. RESULTSWe identified the Stroop Color and Word Test as the largest differentiator for MCI conversion (ROC AUC = 0.795). This was underpinned by disconnectivity in working memory and attention networks. Unsupervised clustering of EEG spectra also differentiated MCI conversion (ROC AUC = 0.710) and was underpinned by reduced excitatory and enhanced inhibitory synaptic efficacy in (prodromal) AD. Combining electrophysiological and neuropsychological assessments increased the accuracy of the differentiation (ROC AUC = 0.880) in comparison to each measure considered individually. CONCLUSIONCombining electrophysiological and neuropsychological assessment with mathematical models can inform the development of non-invasive, low-cost tools for the early diagnosis of AD. HighlightsO_LIWe analysed longitudinal changes in EEG and neuropsychological assessments in MCI C_LIO_LIStroop Color and Word Test error scores were lower in MCI converters C_LIO_LIThe degree of impairment was found to be correlated with functional disconnectivity C_LIO_LIUnsupervised clustering of EEG spectra characterised patterns associated with disease C_LIO_LIMathematical modelling revealed reduced excitatory synaptic efficacy in (prodromal) AD C_LI Research in ContextSystematic review: The authors used PubMed to review the literature on the use of inexpensive modalities, including EEG and neurophysiological testing, for characterising the progression of MCI to AD. Although promising, existing work suggests the full potential of these methods as tools for understanding prodromal AD is still lacking. Interpretation: A novel application of a clustering algorithm to EEG spectra revealed different patient diagnoses could largely be characterised by their cluster assignment. We also found differences in a particular neuropsychological test, the Stroop Color and Word Test. Using mathematical modelling we found there were both network and synaptic mechanisms that underlie these differences. Future directions: Using the methods described herein to build markers for testing MCI to AD conversion on a large independent cohort will be crucial to understanding the full impact and applicability of these approaches. This may ultimately lead to a better characterisation and understanding of the diagnosis and prognosis of AD.

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Dunstan, D. M., Barvas, E., Guttmann, S., Frusciante, R., Viti, B., Volpini, M., Cannuccia, M., Monaldini, C., Tamagnini, F., Goodfellow, M., Tait, L.. 2024-12-17. Longitudinal assessment of the conversion of mild cognitive impairment into Alzheimer's dementia: Observations and mechanisms from neuropsychological testing and electrophysiology. https://doi.org/10.1101/2024.12.16.628666

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Attention Across Scales: From Individual Variation to Social Hierarchies and Brain Networks in Semi-Free-Ranging Macaques

Attention is a fundamental brain function supporting perception, decision-making, and social behavior, and its dysfunction profoundly impairs daily life. It is both dynamic and stable, varying across observations and individuals, changing across the lifespan, and being shaped by social and environmental experience. Yet capturing this complexity remains a central challenge in neuroscience. Here, we integrated longitudinal behavioral assessments of semi-free-ranging macaques living in naturalistic social groups with resting-state fMRI. We quantified performance across days, ages, and social hierarchies and related it to intrinsic brain organization. Distinct attentional phenotypes emerged, including individuals with reduced attentional control. Performance followed an inverted-U lifespan trajectory, improving from childhood to adulthood before declining. Social status modulated attentional performance. Critically, nonlinear lifespan trajectories and associations with individual attentional differences were most clearly expressed in frontoparietal connectivity. Together, these findings reveal how sustained attention is organized across scales, providing a biological framework for its individual diversity, social modulation, and neural basis.

neuroscience↗

bioRxiv2026

Decoding natural scenes from patterned optogenetic responses in mouse visual cortex

A central challenge in developing visual cortical prostheses is to determine how visual stimuli should be transformed into effective patterns of cortical stimulation. Although advances in stimulation technologies, including optogenetics, provide increasingly precise control over cortical activity, it remains unclear whether artificially evoked activity can reproduce the information content of naturally evoked visual representations. Here we establish a quantitative framework for evaluating visual encoding strategies by decoding cortical responses evoked by natural vision and patterned optogenetic stimulation. We developed a novel dual-modal paradigm in awake mice to bridge the gap between endogenous photostimulation and artificial network driving. By co-expressing the high-performance calcium indicator GCaMP6s and the red-shifted, ultra-sensitive opsin rsChRmine-oScarlet in the primary visual cortex (V1), we successfully translated dynamic natural movie frames into patterned, spatiotemporal optogenetic stimulation. Quantitative comparisons of macro-scale dynamics demonstrated that this patterned optogenetic injection evokes cortical states highly comparable and representationally aligned with those driven by actual visual photostimulation. To systematically evaluate the fidelity of these responses, we developed STAR, a deep learning model featuring spatial and temporal attention mechanisms, and successfully reconstructed the frames of natural movies from V1 signals under both experimental modalities. Collectively, our results demonstrate that complex sensory information can be both naturally encoded and synthetically injected into V1 circuits with high decoding fidelity. This work provides an empirical and computational proof-of-concept for intelligent, closed-loop biomimetic encoders, establishing a robust framework for next-generation cortical visual neuroprostheses and bidirectional brain-machine interfaces.

neuroscience↗

bioRxiv2026

Why Is Spontaneous Blink Timing Informative? An Adaptive Scheduling Perspective

Spontaneous eye blinks have long been linked to cognitive processing, yet how task demands shape blink timing and its relationship to behavioral performance remains unclear. We examined spontaneous blink behavior in 576 adults performing two variants of the Continuous Performance Task (CPT). Blink occurrence and timing were most strongly modulated by the experimental condition in the more demanding CPT-AX task, whereas their association with response time was stronger in the CPT-X task, where more consistent blink timing predicted faster responses. This dissociation suggests that task structure changes not only blink behavior but also the behavioral relevance of blink timing. These findings are consistent with an adaptive scheduling account of spontaneous blinking and provide a conceptual framework for understanding when and why blink timing contains chronometric information about ongoing cognition.

neuroscience↗