Brain communications最新文献

{"title":"<i>APOE</i> genotype modulates the impact of sleep duration on locus coeruleus functional connectivity in pre-clinical Alzheimer's disease.","authors":"Liang Gong, Haoyu Li, Maoxia Li, Yuan He, Duan Liu, Wen Zhou, Bei Zhang, Chunhua Xi","doi":"10.1093/braincomms/fcaf341","DOIUrl":"10.1093/braincomms/fcaf341","url":null,"abstract":"<p><p>Sleep duration and Apolipoprotein E genotype are critical factors influencing Alzheimer's disease progression. This study investigates the interaction between sleep duration and Apolipoprotein E genotype on the functional connectivity of the locus coeruleus in clinically unimpaired older adults with elevated amyloid beta, a population at risk for pre-clinical Alzheimer's disease. The study included 692 clinically unimpaired older adults with elevated amyloid beta participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Study (A4). Resting-state functional MRI data were analysed to construct locus coeruleus-based functional connectivity networks, and a 2 × 2 analysis of covariance was conducted to examine the main and interactive effects of sleep duration (normal versus short sleep) and Apolipoprotein E genotype (ɛ4- versus ɛ4+) on locus coeruleus-functional connectivity. Structural equation modelling was used to explore whether locus coeruleus-functional connectivity mediated the relationship between age and cognitive performance. Significant main effects of sleep duration and Apolipoprotein E genotype on locus coeruleus-functional connectivity were observed in the right temporal pole, middle cingulate cortex, and superior temporal gyrus. An interactive effect of sleep and Apolipoprotein E genotype was noted, influencing left locus coeruleus-functional connectivity in regions in the precentral gyrus, and right locus coeruleus-functional connectivity network in the middle temporal gyrus and lateral orbitofrontal cortex. Mediation analysis revealed that locus coeruleus-functional connectivity in the middle cingulate cortex and lateral orbitofrontal cortex partially mediated age associated cognitive decline. These findings suggest that locus coeruleus-functional connectivity networks, influenced by sleep duration and Apolipoprotein E genotype, play a crucial role in cognitive aging, particularly in memory function. Understanding these interactions may inform early intervention strategies to preserve cognitive health in older adults at risk for Alzheimer's disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf341"},"PeriodicalIF":4.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes misaligned in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS): implications for trial design.","authors":"Renae J Stefanetti, Sarah J Charman, Jane Newman, Kate Hallsworth, Alasdair P Blain, Yi Shiau Ng, Gráinne S Gorman","doi":"10.1093/braincomms/fcaf342","DOIUrl":"10.1093/braincomms/fcaf342","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The m.3243A&gt;G variant in the &lt;i&gt;MT-TL1&lt;/i&gt; gene is the most prevalent pathogenic variant in mitochondrial DNA in adults, associated with a wide clinical spectrum from asymptomatic individuals to mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome. Although pharmacological trials in mitochondrial disorders are increasing, the lack of validated endpoints remains a significant barrier to therapeutic development. This cross-sectional observational study aimed to evaluate patients with and without mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome to identify factors associated with disease burden. Seventeen individuals genetically confirmed to harbour the heteroplasmic m.3243A&gt;G pathogenic variant were enrolled: six who met the consensus-based diagnostic criteria for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (median age: 30.0 (inter-quartile range: 29.3-45.0) years). Ten patients who did not have a previous history of stroke-like episodes were assigned as 'non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes' (age: 37.5 (32.8-48.3) years). Of these patients in the non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes group, seven exhibited variable features of mitochondrial disease, including hearing loss, diabetes mellitus, migraine and gastrointestinal involvement, while the remaining three were asymptomatic. One patient was excluded from analysis due to a confirmed ischaemic stroke unrelated to mitochondrial disease. Assessments included disease severity (Newcastle mitochondrial disease adult scale) and patient-reported outcomes of fatigue (fatigue impact scale), health-related quality of life (Newcastle Mitochondrial-QoL), mental well-being (Warwick-Edinburgh mental wellbeing scale), autonomic symptoms (the composite autonomic symptom) and physical activity (The International Physical Activity Questionnaire). Performance outcomes included timed-up and go, handgrip strength, cardiopulmonary exercise testing and accelerometry. Age- and sex-matched healthy controls were included for comparison of accelerometry data (age: 35.5 (28.8-50.5) years). Despite comparable age and mitochondrial DNA heteroplasmy, patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome had significantly higher disease burden, reduced exercise capacity and lower levels of objectively measured physical activity compared to non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes and controls (&lt;i&gt;P&lt;/i&gt; &lt; 0.05-0.001). Patient-reported outcomes did not significantly differ between mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome/non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. While non-mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes patients showed expected alignment between ","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf342"},"PeriodicalIF":4.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High frequency opportunities for Alzheimer's disease.","authors":"Christos Panagiotis Lisgaras","doi":"10.1093/braincomms/fcaf328","DOIUrl":"10.1093/braincomms/fcaf328","url":null,"abstract":"<p><p>This scientific commentary refers to 'High-frequency oscillations in epileptic and non-epileptic Alzheimer's disease patients and the differential effect of levetiracetam on the oscillations', by Shandilya <i>et al</i>. (https://doi.org/10.1093/braincomms/fcaf041).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf328"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian rhythms are associated with higher amyloid-β and tau and poorer cognition in older adults.","authors":"Joanna L Eckhardt, Lisette Isenberg, Vahan Aslanyan, Teresa Monreal, Joy Stradford, Laura Fenton, Joey A Contreras, Wendy J Mack, Judy Pa","doi":"10.1093/braincomms/fcaf322","DOIUrl":"10.1093/braincomms/fcaf322","url":null,"abstract":"<p><p>Several studies implicate circadian rhythm disturbances in Alzheimer's disease. However, very little is known about how circadian rhythms are associated with Alzheimer's pathological biomarkers in older adults at early stages of the disease, and how these relationships map onto cognition. This cross-sectional study used 24-h accelerometry data to investigate the relationships between circadian rhythms, amyloid-β (Aβ), tau, and cognition in 68 older adults with objective early cognitive impairment. Participants wore GENEActiv accelerometers for ∼1 month (mean = 31.8 days). Circadian rhythms measures were quantified from accelerometer data and included acrotime (average time of day of peak activity) and intradaily variability (IV) (average circadian rhythm fragmentation within a day). Aβ was measured as a composite, and tau (<i>n</i> = 67) was measured in Braak staging regions of interest I/II and III/IV using positron emission tomography. The cognitive domains used were verbal memory (California Verbal Learning Test short delay free recall) and attention/processing speed (Digit Symbol Substitution Test). Multivariable linear regression models were conducted to test for associations between circadian rhythms and the outcome variables of Aβ, tau, and cognition. The moderating effects of age, sex, and <i>apolipoprotein E4</i> (<i>APOE4</i>) carrier status were assessed in these associations. To investigate mechanistic pathways through which circadian rhythms may impact cognition, exploratory mediation analyses were conducted <i>post hoc</i>. Models were adjusted for age, sex, <i>APOE4</i> carrier status, and years of education. The study included 68 older adults (mean age = 66.8 years, age range = 55-80 years, 63.2% female, 26.5% <i>APOE4</i> carriers). Earlier acrotime was associated with higher Aβ and tau, the former of which was stronger in <i>APOE4</i> carriers relative to non-carriers. Higher IV was related to higher tau in Braak regions III/IV. Age and sex modified the association between IV and tau, in which the relationships strengthened with increasing age and disproportionately affected men. Earlier acrotime was associated with worse verbal memory, but later acrotime was associated with worse attention/processing speed. Tau in Braak regions I-IV mediated the relationship between acrotime and verbal memory. The insights from this study revealed that circadian rhythms were associated with Aβ, tau, and cognition in older adults with objective early cognitive impairment. We provide novel evidence for tau as a biological mediator in the relationship between circadian timing and cognition. This work identified circadian rhythms as a promising point of intervention to reduce Alzheimer's disease risk and potentially mitigate pathological progression and cognitive decline.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf322"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopaminergic drugs modulate fear extinction-related processes in humans, but effects are mild.","authors":"Alice Doubliez, Kristina Köster, Lara Müntefering, Enzo Nio, Nicolas Diekmann, Andreas Thieme, Bilge Albayrak, Seyed Ali Nicksirat, Friedrich Erdlenbruch, Giorgi Batsikadze, Thomas Michael Ernst, Sen Cheng, Christian Josef Merz, Dagmar Timmann","doi":"10.1093/braincomms/fcaf333","DOIUrl":"10.1093/braincomms/fcaf333","url":null,"abstract":"<p><p>The ability to extinguish learned fear responses is crucial for adaptive behaviour. The mesolimbic dopaminergic system originating in the ventral tegmental area has been proposed to contribute to fear extinction learning because of its critical role in reward learning. The unexpected omission of aversive unconditioned stimuli (US) is considered rewarding (outcome better than expected) and drives extinction learning. We tested the hypothesis that extinction learning is facilitated by dopaminergic drugs and impeded by anti-dopaminergic drugs. The effects of dopamine agonists [levodopa (100 mg) and bromocriptine (1.25 mg)] and antagonists [tiapride (100 mg) and haloperidol (3 mg)] on fear extinction learning were compared with placebo in 146 young and healthy human participants. A 3-day differential fear-conditioning paradigm was performed with pupil size and skin conductance responses (SCRs) being recorded. Participants underwent fear acquisition training on Day 1, extinction training on Day 2 and recall on Day 3. The conditioned stimuli (CS+, CS-) consisted of two geometric figures. A short electrical stimulation was used as the aversive US. One of the four drugs or placebo was administered prior to the extinction phase on Day 2. Overall, effects were small and seen only in the bromocriptine group. In accordance with our hypothesis, we measured reduced pupil dilation during late recall in the bromocriptine group compared with the placebo group, indicating faster re-extinction of spontaneously recovered fear reactions on the third day. The effects of levodopa and haloperidol were unspecific and related to generally increased SCR levels in the levodopa group (already prior to drug intake) and miotic side-effects of haloperidol. These findings provide additional support that the dopaminergic system contributes to extinction learning in humans, possibly by improving consolidation of fear extinction memory.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf333"},"PeriodicalIF":4.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated plasma p-tau217 in newborns: developmental signal or synaptic stress marker?","authors":"Caterina Motta, Chiara Giuseppina Bonomi, Alessandro Martorana","doi":"10.1093/braincomms/fcaf335","DOIUrl":"10.1093/braincomms/fcaf335","url":null,"abstract":"<p><p>The finding of elevated plasma p-tau217 in newborns raises the question of whether it represents a developmental signal or an early marker of synaptic stress, offering new insights into the biology of tau in the human brain.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf335"},"PeriodicalIF":4.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-modal approach for the treatment of non-fluent/agrammatic variant of Primary Progressive Aphasia.","authors":"Maria Cotelli, Ilaria Pagnoni, Elena Gobbi, Elena Campana, Sonia Bellini, Antonio Longobardi, Claudia Saraceno, Andrea Geviti, Valentina Cantoni, Antonella Alberici, Enrico Premi, Barbara Borroni, Roberta Ghidoni, Giuliano Binetti, Rosa Manenti","doi":"10.1093/braincomms/fcaf295","DOIUrl":"10.1093/braincomms/fcaf295","url":null,"abstract":"<p><p>The non-fluent/agrammatic variant of primary progressive aphasia is a neurodegenerative disorder characterized by effortful language production and impaired comprehension of grammatically complex sentences. Recently, interest in non-pharmacological interventions has increased, particularly regarding techniques that allow for non-invasive brain stimulation, such as transcranial direct current stimulation. The main purpose of this study was to investigate whether the use of anodal transcranial direct current stimulation applied to the dorsolateral prefrontal cortex during individualized language training for 25 min a day at 5 days a week for 2 weeks would lead to significant oral naming improvements in patients with agrammatic variant of primary progressive aphasia. Specifically, we hypothesized that anodal transcranial direct current stimulation plus individualized language training may improve the oral naming of treated and untreated objects compared with both placebo transcranial direct current stimulation plus individualized language therapy and anodal transcranial direct current stimulation combined with computerized cognitive training. Forty-seven agrammatic variant of primary progressive aphasia patients were consecutively enrolled and randomized into one of three groups that received the following treatments: (i) anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex during individualized language rehabilitation treatment; (ii) placebo transcranial direct current stimulation during individualized language rehabilitation treatment; or (iii) anodal transcranial direct current stimulation with computerized cognitive training. Clinical, neuropsychological and language assessments were recorded at baseline (T0), post-treatment (T1, 2 weeks) and at 12 weeks from T0 (T2). Magnetic resonance imaging data, functional magnetic resonance imaging data and blood samples were collected at T0 and T1. All of the groups demonstrated improvements in oral object naming at T1, with maintenance effects being observed at T2. At T1, the enhancement in the oral naming of treated and untreated objects was significantly greater in patients who underwent anodal transcranial direct current stimulation during individualized language rehabilitation treatment. There were no significant changes observed across the groups regarding the magnetic resonance imaging, functional magnetic resonance imaging or blood biochemical marker data. Our results support the beneficial effects of individualized language rehabilitation treatment in combination with anodal transcranial direct current stimulation in agrammatic variant of primary progressive aphasia patients.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf295"},"PeriodicalIF":4.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic <i>CRELD1</i> variants cause severe muscle weakness and infantile epilepsy.","authors":"Manuela D'Alessandro, Daniel Bamborschke, Margret H Bülow, Özkan Özdemir, Hülya-Sevcan Daimagüler, Verena Brümmer, Nicole Kucharowski, Julia Sellin, Anna Brunn, Martina Deckert, Gilbert Wunderlich, Friederike Koerber, Jean-Louis Bessereau, Sebahattin Cirak","doi":"10.1093/braincomms/fcaf326","DOIUrl":"10.1093/braincomms/fcaf326","url":null,"abstract":"<p><p>Nicotinic acetylcholine receptors are widely expressed in the peripheral and central nervous systems. Mutations in acetylcholine receptor-subunit genes have been associated with neuromuscular diseases, such as arthrogryposis multiplex congenita (AMC) and epilepsy. We report a patient with arthrogryposis, severe muscle weakness and neurodevelopmental delay. During his first year of life, he developed therapy-refractory epilepsy. Using whole-exome sequencing, we identified the compound pathogenic variants c. 875G>A (p. Cys292Tyr) and c. 959delA (p. Gln320Argfs*25) in the cysteine-rich with epidermal growth factor-like domain protein 1 gene (<i>CRELD1</i>, NM_001077415.3). Recently, functional studies have shown that CRELD1 is a membrane-associated endoplasmic reticulum-resident protein disulphide isomerase that acts as a maturation enhancer of AChR biogenesis, thereby controlling the abundance of functional receptors at the cell surface. To test pathogenicity, we took advantage of the genetics and extremely rapid genome editing in <i>Caenorhabditis elegans</i>. We were able to model these heterozygous variants and observed a decrease in AChRs at the neuromuscular junction. Hence, our study identifies compound heterozygous <i>CRELD1</i> variants responsible for a rare neurodevelopmental disorder characterized by arthrogryposis, muscle weakness and epilepsy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf326"},"PeriodicalIF":4.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of anterior callosal disconnection on picture naming in frontal lobe epilepsy surgery.","authors":"Davide Giampiccolo, Lawrence P Binding, Umesh Vivekananda, Zara Fenlon, Roman Rodionov, Jane de Tisi, Fenglai Xiao, Aidan O'Keeffe, Andrew W McEvoy, Fahmida A Chowdhury, Sallie A Baxendale, Anna Miserocchi, John S Duncan","doi":"10.1093/braincomms/fcaf317","DOIUrl":"10.1093/braincomms/fcaf317","url":null,"abstract":"<p><p>Epilepsy surgery in focal, drug-resistant frontal lobe epilepsy can be curative and resection is aimed at seizure freedom. The cognitive impact of surgery, however, is less clear-cut. On one hand, resection of the epileptogenic zone can disconnect essential brain networks and therefore cause dysfunction. On the other hand, surgery may prompt recovery of normal brain function by restoring normal electrical activity as propagating epileptic discharges affect cognition outside the epileptogenic zone. To understand the impact of surgery on cognitive outcome, we investigated picture naming in 51 patients undergoing frontal lobe epilepsy surgery (28 left-hemisphere-dominant; 23 language-dominant) preoperatively and at 12 months follow-up using complementary voxel-based lesion symptom mapping, tractwise voxel-based disconnectome and tractography analyses to investigate cortical regions and white matter structures associated with language performance. Naming performance significantly improved 1 year after surgery compared with preoperatively, irrespective of the operated hemisphere or dominance. Improved naming performance was associated with freedom from seizures with impaired awareness. No damage to any region or white matter structure was associated with language decline. Voxel-based disconnectome analysis identified a region in the anterior corpus callosum associated with improved naming. This was confirmed by the tractography disconnectome analysis showing that naming improvement was linked to anterior callosal disconnection between regions linking presupplementary/supplementary motor areas, posterior middle frontal and inferior frontal gyri bilaterally. Our results suggest that seizure reduction can underlie language improvement: in line with results from hemispherotomy or callosotomy, isolating epileptic activity from the language network through callosal disconnection may support cognitive recovery.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf317"},"PeriodicalIF":4.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A passive and objective measure of recognition memory in mild cognitive impairment using Fastball memory assessment.","authors":"George Stothart, Sophie Alderman, Oliver Hermann, Sam Creavin, Elizabeth J Coulthard","doi":"10.1093/braincomms/fcaf279","DOIUrl":"10.1093/braincomms/fcaf279","url":null,"abstract":"<p><p>As viable pharmacotherapies and blood biomarkers emerge for dementia treatment and screening, there remains a great need for accurate, sensitive biomarkers of cognitive function. We have previously demonstrated that Fastball, a new Electroencephalography (EEG) method for the passive and objective measurement of recognition memory that requires no behavioural memory response or task comprehension, is sensitive to cognitive dysfunction in Alzheimer's disease. Here we present new evidence that Fastball is sensitive to amnestic dysfunction in an earlier stage of the dementia lifecourse, Mild Cognitive Impairment (MCI). 53 MCI patients and 54 healthy older adult (HOA) controls completed a 3-min Fastball task in which they passively viewed rapidly presented images while EEG captured their automatic ability to differentiate between images based on previous exposure. They also completed neuropsychological assessments of memory (Delayed Match to Sample-48), sustained attention (Psychomotor Vigilance Task), and general cognitive function (Addenbrookes Cognitive Exam-iii). Participants were re-tested after 1 year to establish the test-retest reliability of Fastball in HOAs, and the sensitivity of Fastball to cognitive decline in MCI patients, over a 1 year period. Amnestic MCI patients showed significantly reduced Fastball responses compared with non-amnestic MCI patients (<i>P</i> = 0.001, Cohen's <i>d</i> = 0.98) and HOA controls (<i>P</i> = 0.005, Cohen's <i>d</i> = 0.64). Regression analyses showed that Fastball EEG responses were selectively predictive of neuropsychological measures of recognition memory and not attention. Between baseline and year one follow-up Fastball showed moderate to good test-retest reliability in HOA controls, and the six MCI-dementia converters showed a trend for lower Fastball responses at baseline which will be confirmed with further longitudinal assessment. Fastball is further validated as a viable method for testing recognition memory in cognitively impaired populations. We have demonstrated that it is selectively predictive of memory dysfunction and not attention or other cognitive functions. It is passive, non-invasive, quick to administer and uses cheap, scalable EEG technology. Fastball is a viable functional biomarker that can help to advance cognitive assessment in MCI.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 5","pages":"fcaf279"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}