Middle Temporal Cortex Research Articles

Detection of Alzheimer's Disease Using Hybrid Meta-ROI of MRI Structural Images.

The averaged cortical thickness of meta-ROI is currently being used for the diagnosis and prognosis of Alzheimer's disease (AD) using structural MRI brain images. The purpose of this work is to present a hybrid meta-ROI for the detection of AD. The AD detectability of selected cortical and volumetric regions of the brain was examined using signal detection theory. The top performing cortical and volumetric ROIs were taken as input nodes to the artificial neural network (ANN) for AD classification. An AD diagnostic accuracy of 91.9% was achieved by using a hybrid meta-ROI consisting of thicknesses of entorhinal and middle temporal cortices, and the volumes of the hippocampus and inferior lateral ventricles. Pairing inferior lateral ventricle dilation with hippocampal volume reduction improves AD detectability by 5.1%. Hybrid meta-ROI, including the dilation of inferior lateral ventricles, outperformed both cortical thickness- and volumetric-based meta-ROIs in the detection of Alzheimer's disease.

Motor versus Psychomotor? Deciphering the Neural Source of Psychomotor Retardation in Depression.

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

FNIRS Changes in the Middle Temporal and Occipital Cortices After a Cochlear Implant.

The relationship between the middle temporal (MTG) and occipital cortices in post-lingually deaf (PLD) individuals is unclear. This study aimed to investigate changes in the MTG and occipital cortices excitability and their effects on the occipital cortex in individuals with PLD after receiving a cochlear implant (CI). Twenty-six individuals with severe-to-profound binaural sensorineural PLD were assessed clinically. Nine individuals had received a unilateral cochlear implant over 6 months, while 17 had not. Brodmann area 19 (BA19, extra-striate occipital cortex) and MTG (auditory-related area of cortex) were selected as regions of interest. The excitability of the ROI was observed and compared in the surgery and no-surgery groups by functional near-infrared spectroscopy (fNIRS) in the resting state, and correlations between connectivity of the MTG and occipital cortex, and as well as the duration of time that had elapsed following CI surgery, were investigated. fNIRS revealed enhanced global cortical connectivity in the BA19 and MTG on the operative side (p < 0.05) and the connectivity between BA19 and the MTG also increased (p < 0.05). The connectivity between the MTG and BA19 was positively correlated with the duration of cochlear implantation, as was the case for BA18. There was evidence for remodeling of the cerebral cortex: increased excitability was observed in the MTG and BA19, and their connectivity was enhanced, indicating a synergistic effect. Moreover, the MTG may further stimulate the visual cortex by strengthening their connectivity after CI. 3 Laryngoscope, 2024.

Associations of alcohol and tobacco use with psychotic, depressive and developmental disorders revealed via multimodal neuroimaging

People affected by psychotic, depressive and developmental disorders are at a higher risk for alcohol and tobacco use. However, the further associations between alcohol/tobacco use and symptoms/cognition in these disorders remain unexplored. We identified multimodal brain networks involving alcohol use (n = 707) and tobacco use (n = 281) via supervised multimodal fusion and evaluated if these networks affected symptoms and cognition in people with psychotic (schizophrenia/schizoaffective disorder/bipolar, n = 178/134/143), depressive (major depressive disorder, n = 260) and developmental (autism spectrum disorder/attention deficit hyperactivity disorder, n = 421/346) disorders. Alcohol and tobacco use scores were used as references to guide functional and structural imaging fusion to identify alcohol/tobacco use associated multimodal patterns. Correlation analyses between the extracted brain features and symptoms or cognition were performed to evaluate the relationships between alcohol/tobacco use with symptoms/cognition in 6 psychiatric disorders. Results showed that (1) the default mode network (DMN) and salience network (SN) were associated with alcohol use, whereas the DMN and fronto-limbic network (FLN) were associated with tobacco use; (2) the DMN and fronto-basal ganglia (FBG) related to alcohol/tobacco use were correlated with symptom and cognition in psychosis; (3) the middle temporal cortex related to alcohol/tobacco use was associated with cognition in depression; (4) the DMN related to alcohol/tobacco use was related to symptom, whereas the SN and limbic system (LB) were related to cognition in developmental disorders. In summary, alcohol and tobacco use were associated with structural and functional abnormalities in DMN, SN and FLN and had significant associations with cognition and symptoms in psychotic, depressive and developmental disorders likely via different brain networks. Further understanding of these relationships may assist clinicians in the development of future approaches to improve symptoms and cognition among psychotic, depressive and developmental disorders.

Abnormal functional connectivity of the putamen in obsessive-compulsive disorder

The putamen has been proposed to play a critical role in the development of obsessive-compulsive disorder (OCD). The primary objective of this study was to examine the resting-state regional activity and functional connectivity patterns of the putamen in individuals diagnosed with OCD. To achieve this, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to collect data from a sample of 45 OCD patients and 53 healthy control participants. We aimed to use the regional amplitude of low-frequency fluctuation (ALFF) analysis to generate the ROI masks of the putamen and then conduct the whole brain functional connectivity of the putamen in individuals with OCD. Compared to controls, the OCD group demonstrated decreased ALFF in bilateral putamen. The right putamen also displayed decreased FC with the left putamen extending to the inferior frontal gyrus (IFG), bilateral precuneus extending to calcarine, the right middle occipital cortex extending to the right middle temporal cortex, and the left middle occipital gyrus. The decreased connectivity between the right putamen and the left IFG was negatively correlated with Yale-Brown Obsessive Compulsive scale (Y-BOCS) Obsession Scores. This study aimed to reveal the putamen changes in resting-state activity and connectivity in OCD patients, highlighting the significance of aberrant ALFF/FC of the putamen is a key characteristic of OCD.

Visual perspective taking neural processing in forensic cases with high density EEG

This EEG study aims at dissecting the differences in the activation of neural generators between borderline personality disorder patients with court-ordered measures (BDL-COM) and healthy controls in visual perspective taking. We focused on the distinction between mentalizing (Avatar) and non-mentalizing (Arrow) stimuli as well as self versus other-perspective in the dot perspective task (dPT) in a sample of 15 BDL-COM cases and 54 controls, all of male gender. BDL-COM patients showed a late and diffuse right hemisphere involvement of neural generators contrasting with the occipitofrontal topography observed in controls. For Avatars only and compared to controls, the adoption of Self perspective involved a lower EEG activity in the left inferior frontal, right middle temporal cortex and insula in BDL-COM patients prior to 80 ms post-stimulus. When taking the Other-perspective, BDL-COM patients also showed a lower activation of superior frontal, right inferior temporal and fusiform cortex within the same time frame. The beta oscillation power was significantly lower in BDL-COM patients than controls between 400 and 1300 ms post stimulus in the Avatar-Other condition. These results indicate that BDL-COM patients display both altered topography of EEG activation patterns and reduced abilities to mobilize beta oscillations during the treatment of mentalistic stimuli in dPT.

Relation Between Abnormal Spontaneous Brain Activity and Altered Neuromuscular Activation of Lumbar Paraspinal Muscles in Chronic Low Back Pain

ObjectiveTo investigate the neural mechanism underlying functional reorganization and motor coordination strategies in patients with chronic low back pain (cLBP). DesignA case-control study based on data collected during routine clinical practice. SettingThis study was conducted at a university hospital. ParticipantsFifteen patients with cLBP and 15 healthy controls. InterventionsNot applicable. Main Outcome MeasuresWhole brain blood oxygen level-dependent signals were measured using functional magnetic resonance imaging and amplitude of low-frequency fluctuation (ALFF) method to identify pain-induced changes in regional spontaneous brain activity. A novel approach based on the surface electromyogram (EMG) system and fine-wire electrodes was used to record EMG signals in the deep multifidus, superficial multifidus, and erector spinae. ResultsIn cLBP, compared with healthy groups, ALFF was higher in the medial prefrontal, primary somatosensory, primary motor, and inferior temporal cortices, whereas it was lower in the cerebellum and anterior cingulate and posterior cingulate cortices. Furthermore, the decrease in the average EMG activity of the 3 lumbar muscles in the cLBP group was positively correlated with the ALFF values of the primary somatosensory cortex, motor cortex, precuneus, and middle temporal cortex but significantly negatively correlated with the ALFF values of the medial prefrontal and inferior temporal cortices. Interestingly, the correlation between the functional activity in the cerebellum and the EMG activity varied in the lumbar muscles. ConclusionsThese findings suggest a functional association between changes in spontaneous brain activity and altered voluntary neuromuscular activation patterns of the lumbar paraspinal muscles, providing new insights into the mechanisms underlying pain chronicity as well as important implications for developing novel therapeutic targets of cLBP.

Family and parenting factors are associated with emotion regulation neural function in early adolescent girls with elevated internalizing symptoms.

A prominent tripartite model proposes that parent role modeling of emotion regulation, emotion socialization behaviors, and the emotional climate of the family are important for young people's emotional development. However, limited research has examined the neural mechanisms at play. Here, we examined the associations between family and parenting factors, the neural correlates of emotional reactivity and regulation, and internalizing symptoms in early adolescent girls. Sixty-four female adolescents aged 10-12 years with elevated internalizing symptoms completed emotional reactivity, implicit (affect labeling) and explicit (cognitive reappraisal) emotion regulation tasks during functional magnetic resonance imaging. Positive family emotional climate was associated with greater activation in the anterior cingulate and middle temporal cortices during emotional reactivity. Maternal emotion regulation difficulties were associated with increased frontal pole and supramarginal gyrus activation during affect labeling, whereas supportive maternal emotion socialization and positive family emotional climate were associated with activation in prefrontal regions, including inferior frontal and superior frontal gyri, respectively, during cognitive reappraisal. No mediating effects of brain function were observed in the associations between family/parenting factors and adolescent symptoms. These findings highlight the role of family and parenting behaviors in adolescent emotion regulation neurobiology, and contribute to prominent models of adolescent emotional development.

The multiscale topological organization of the functional brain network in adolescent PTSD.

The experience of an extremely aversive event can produce enduring deleterious behavioral, and neural consequences, among which posttraumatic stress disorder (PTSD) is a representative example. Although adolescence is a period of great exposure to potentially traumatic events, the effects of trauma during adolescence remain understudied in clinical neuroscience. In this exploratory work, we aim to study the whole-cortex functional organization of 14 adolescents with PTSD using a data-driven method tailored to our population of interest. To do so, we built on the network neuroscience framework and specifically on multilayer (multisubject) community analysis to study the functional connectivity of the brain. We show, across different topological scales (the number of communities composing the cortex), a hyper-colocalization between regions belonging to occipital and pericentral regions and hypo-colocalization in middle temporal, posterior-anterior medial, and frontal cortices in the adolescent PTSD group compared to a nontrauma exposed group of adolescents. These preliminary results raise the question of an altered large-scale cortical organization in adolescent PTSD, opening an interesting line of research for future investigations.

Unraveling the causal relationships between depression and brain structural imaging phenotypes: A bidirectional Mendelian Randomization study

BackgroundPrevious studies have revealed structural brain abnormalities in individuals with depression, but the causal relationship between depression and brain structure remains unclear. MethodsA genetic correlation analysis was conducted using summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 1,265 brain structural imaging-derived phenotypes (IDPs, N = 33,224). Subsequently, a bidirectional two-sample Mendelian Randomization (MR) approach was employed to explore the causal relationships between depression and the IDPs that showed genetic correlations with depression. The main MR results were obtained using the inverse variance weighted (IVW) method, and other MR methods were further employed to ensure the reliability of the findings. ResultsNinety structural IDPs were identified as being genetically correlated with depression and were included in the MR analyses. The IVW MR results indicated that reductions in the volume of several brain regions, including the bilateral subcallosal cortex, right medial orbitofrontal cortex, and right middle-posterior part of the cingulate cortex, were causally linked to an increased risk of depression. Additionally, decreases in surface area of the right middle temporal visual area, right middle temporal cortex, right inferior temporal cortex, and right middle-posterior part of the cingulate cortex were causally associated with a heightened risk of depression. Validation and sensitivity analyses supported the robustness of these findings. However, no evidence was found for a causal effect of depression on structural IDPs. ConclusionsOur findings reveal the causal influence of specific brain structures on depression, providing evidence to consider brain structural changes in the etiology and treatment of depression.

Hearing what is being said: the distributed neural substrate for early speech interpretation

ABSTRACT Speech comprehension is remarkable for the immediacy with which the listener hears what is being said. Here, we focus on the neural underpinnings of this process in isolated spoken words. We analysed source-localised MEG data for nouns using Representational Similarity Analysis to probe the spatiotemporal coordinates of phonology, lexical form, and the semantics of emerging word candidates. Phonological model fit was detectable within 40–50 ms, engaging a bilateral network including superior and middle temporal cortex and extending into anterior temporal and inferior parietal regions. Lexical form emerged within 60–70 ms, and model fit to semantics from 100-110 ms. Strikingly, the majority of vertices in a central core showed model fit to all three dimensions, consistent with a distributed neural substrate for early speech analysis. The early interpretation of speech seems to be conducted in a unified integrative representational space, in conflict with conventional views of a linguistically stratified representational hierarchy.

Investigating the neural basis of schematic false memories by examining schematic and lure pattern similarity

ABSTRACT Schemas allow us to make assumptions about the world based upon previous experiences and aid in memory organisation and retrieval. However, a reliance on schemas may also result in increased false memories to schematically related lures. Prior neuroimaging work has linked schematic processing in memory tasks to activity in prefrontal, visual, and temporal regions. Yet, it is unclear what type of processing in these regions underlies memory errors. The current study examined where schematic lures exhibit greater neural similarity to schematic targets, leading to this memory error, as compared to neural overlap with non-schematic lures, which, like schematic lures, are novel items at retrieval. Results showed that patterns of neural activity in ventromedial prefrontal cortex, medial frontal gyrus, middle temporal gyrus, hippocampus, and occipital cortices exhibited greater neural pattern similarity for schematic targets and schematic lures than between schematic lures and non-schematic lures. As such, results suggest that schematic membership, and not object history, may be more critical to the neural processes underlying memory retrieval in the context of a strong schema.

Study of vision-related resting-state activity in suprasellar tumor patients with postoperative visual damage.

The objective of this study was to investigate changes in vision-related resting-state activity in patients with suprasellar tumors (ST) who experienced vision deterioration after surgery. Twelve patients with ST and vision deterioration after surgery were included in the study. Resting-state functional connectivity (FC) was compared before and after surgery using a seed-based analysis with a priori specified regions of interest (ROIs) within the visual areas. The differences between the two groups were identified using a paired t-test. The data showed a decrease in FC within and between the dorsal and ventral pathways, as well as in the third pathway in ST patients. The middle temporal visual cortex (MT+) showed a decreased FC with more regions than other visual ROIs. The data also revealed an increase in FC between the visual ROIs and higher-order cortex. The superior frontal gyrus/BA8 showed an increased FC with more ROIs than other high-order regions, and the hOC4d was involved in an increased FC with more high-order regions than other ROIs. The study results indicate significant neural reorganization in the vision-related cortex of ST patients with postoperative vision damage. Most subareas within the visual cortex showed remarkable neural dysfunction, and some highe-order cortex may be primarily involved in top-down control of the subareas within the visual cortex. The hot zones may arise in the processing of "top-down" influence.

Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants.

We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle-aged and older adults. Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume. AD-GRS modified the estimated effect of age (per decade) on the amygdala (-0.41 mm3 [-0.42, -0.40]); hippocampus (-0.45 mm3 [-0.45, -0.44]), nucleus accumbens (-0.55 mm3 [-0.56, -0.54]), thalamus (-0.38 mm3 [-0.39, -0.37]), and medial orbitofrontal cortex (-0.23 mm3 [-0.24, -0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD-GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices. APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

Reduced slow‐wave sleep is associated with greater tau accumulation and reduced cortical thickness in the temporal lobe

AbstractBackgroundSlow wave sleep (SWS) plays an important role in overnight memory consolidation and promotes overnight clearance of amyloid‐β and tau proteins. Reduced SWS has been associated with higher amyloid burden in CSF in preclinical stages of Alzheimer’s disease (AD). However, little is known about the relationship between SWS, tau burden and neurodegeneration in cognitively unimpaired (CU) adults. Thus, we investigated the relationships between slow‐wave sleep, regional tau PET (18F‐flortaucipir; FTP‐PET) and temporal lobe cortical thickness in cognitively unimpaired adults at risk of AD.MethodsThis study included 39 CU adults from the Harvard Aging Brain Study (mean age 74.6 years, 61.5% females) who underwent at‐home polysomnography (PSG; Compumedics Somte), tau PET (FTP‐PET, amyloid PET (PIB‐PET) and MRI (Table 1). We used separate multivariate linear regressions to assess associations between the percentage of slow‐wave sleep (SWS) and tau PET signal in the following ROIs: entorhinal cortex, inferior temporal cortex, and a temporal composite comprised of entorhinal, inferior temporal, middle temporal and fusiform cortices. Primary analyses were adjusted for age and sex. Secondary analyses also adjusted for global amyloid (PiB‐PET) burden. Lastly, we investigated the relationship between SWS and cortical thickness in the same ROIs, assessed using FreeSurfer v6.0.ResultsLower percentage of SWS was associated with greater tau burden in entorhinal (p = 0.036), inferior temporal (p = 0.011), and temporal composite ROIs (p = 0.005). Associations between reduced SWS and greater FTP‐PET signal in the inferior temporal cortex and temporal composite ROI remained after controlling for PiB‐PET (p = 0.028; p = 0.017, respectively; Table 2). Additionally, lower SWS was associated with reduced cortical thickness in the entorhinal (p = 0.031), inferior temporal (p = 0.023) and temporal composite ROIs (p = 0.002) (Table 3).ConclusionsLower SWS in CU adults was associated with higher tau burden in regions of the temporal lobe that are commonly sites of early tau accumulation. These effects were independent of amyloid burden, suggesting disrupted sleep may lead to increased tau accumulation via an amyloid‐independent pathway. Importantly, lower SWS was also associated with reduced cortical thickness in temporal regions, suggesting that disrupted sleep may be tied to early AD‐related neuronal loss in the temporal lobe.

Does texture analysis classify semantic dementia from Alzheimer’s disease better than volumetric analysis?

AbstractBackgroundTexture analysis may capture subtle changes in the gray matter more sensitively than volumetric analysis. We aimed to investigate the patterns of neurodegeneration in semantic dementia (SD) and Alzheimer’s disease (AD) by comparing the temporal gray matter texture and volume between cognitively normal controls and older adults with SD and AD.MethodWe enrolled all participants from three national university hospitals in Korea. We obtained T1‐weighted magnetic resonance images and compared the gray matter texture and volume of regions of interest (ROIs) between the groups using analysis of variance with Bonferroni posthoc comparisons. We also developed models for classifying SD, AD and control groups using logistic regression analyses, and validated the models using receiver operator characteristics analysis.ResultCompared to the AD group, the SD group showed lower volumes in five ROIs (bilateral temporal poles, and the left inferior, middle, and superior temporal cortices) and higher texture in these five ROIs and two additional ROIs (right inferior temporal and left entorhinal cortices). The performances of both texture‐ and volume‐based models were good and comparable in classifying SD from NC (mean area under the curve [AUC] = 0.914 for texture; mean AUC = 0.894 for volume). However, only the texture‐based model achieved a good level of performance in classifying SD and AD (mean AUC = 0.775 for texture; mean AUC = 0.658 for volume).ConclusionTexture may be a useful neuroimaging marker for early detection of SD in older adults and its differentiation from AD.

Enhanced arterial spin labeling in mild cognitive impairment phenotypes

AbstractBackgroundArterial spin labeling perfusion MRI is increasingly proving to be a promising tool for exploring neurovascular changes in neurodegenerative conditions. Using an advanced 3D pseudo‐continuous arterial spin labeling sequence with Hadamard‐encoded multiple post‐labeling delays (eASL), this study evaluated both cerebral blood flow (CBF) and arterial transit time (ATT) alterations in mild cognitive impairment (MCI) phenotypes.MethodMCI patients (N = 19;Mage = 74.63±5.65) and controls (N = 20;Mage = 70.04±7.06) underwent a 3T MR scan with the eASL sequence. ATT and CBF were simultaneously measured. Voxel‐wise group comparisons of CBF and ATT were performed. Results were thresholded at a cluster‐size corrected p&lt;0.001 (a&lt;0.05). A region of interest (ROI) was defined as the overlap of clusters showing a significant difference in CBF and ATT between MCI and controls. Independent t‐tests between MCI phenotypes (amnestic, non‐amnestic) and controls on CBF and ATT ROIs were conducted. Pearson correlations of ROIs with measures of cognition, including executive functioning, were calculated. Correlations informed regression analysis.ResultsVoxelwise analyses (Figure1) demonstrated decreased CBF in MCI compared to controls in the default mode network, middle and superior frontal gyri, inferior parietal lobule, and temporal lobe. Increased ATT was seen in similar regions, with clusters centered in inferior and middle temporal lobe and visual cortex. T‐tests using created ROIs (as described above) revealed group differences between controls and MCI phenotypes in both CBF and ATT (ps≤.01); there was a non‐significant trend for higher ATT in naMCI versus aMCI. The highest correlational values emerged between CBF and ATT ROIs with a measure of executive functioning (TrailsB). IVs in regression analysis were age (step 1) and ATT and CBF overlapping ROI values (step 2, stepwise); TrailsB = DV . Across the entire cohort, CBF (R2 change = .239, p&lt;.001), not ATT, was included in the model.ConclusionAdvanced 3D pCASL with Hadamard encoded multiple PLDs (eASL) can be used to simultaneously measure CBF and ATT in MCI and controls. MCI patients showed different patterns of reduced CBF and prolonged ATT. While CBF and ATT values were significantly correlated with TrailsB, regression analysis revealed that CBF was a more robust predictor of TrailsB. Future research should examine eASL as a biomarker for MCI phenotypes.

Associations of APOE4 and Alzheimer’s disease biomarkers with cortical reinstatement and episodic memory in clinically unimpaired older adults

AbstractBackgroundCortical reinstatement is a key neural correlate of episodic remembering across the lifespan and explains significant variability in memory performance among older adults. We assessed whether Alzheimer’s disease (AD) risk factors – cerebrospinal fluid (CSF) Aβ42/Aβ40, CSF pTau181, plasma pTau181, and APOE genotype – impact cortical reinstatement in clinically unimpaired older adults.MethodParticipants were 150 clinically unimpaired older adults enrolled in the Stanford Aging and Memory Study (SAMS). APOE genotype was determined from whole‐genome sequencing and participants were classified as ε4 carriers (N = 38) or non‐carriers (N = 112). CSF Aβ42/Aβ40 and pTau181 and plasma pTau181 were quantified using the automated Lumipulse G system. Cortical reinstatement was quantified during successful retrieval of word‐picture associations using fMRI multivoxel pattern analysis (MVPA) in five regions of interest, including parahippocampal gyrus (PHG), ventral temporal cortex (VTC), middle temporal gyrus (MTG), angular gyrus (ANG), and posterior medial cortex (PMC). Regression analyses examined cross‐sectional relationships between regional cortical reinstatement and a) APOE genotype (N = 150), b) CSF Aβ42/Aβ40 and pTau181 (N = 113), and (c) plasma pTau181 (N = 140), as well as associations of these variables with associative memory discrimination (d’). All models included age, sex, and regional MVPA classifier accuracy during memory encoding.ResultAPOE ε4 genotype was negatively associated with reinstatement strength in VTC (β = ‐0.54, p &lt; .005), MTG (β = ‐0.32, p &lt; .05), and ANG (β = ‐0.32, p &lt; .05) and CSF Aβ42/Aβ40 burden was linked to weaker reinstatement in ANG (β = 0.16, p &lt; .05). In VTC, the effect of APOE ε4 on reinstatement remained significant after controlling for CSF Aβ42/Aβ40 (β = ‐0.47, p &lt; .05); a similar pattern was observed in MTG and ANG. Although CSF pTau181 was unrelated to reinstatement strength, both pTau181 and cortical reinstatement explained unique variance in memory performance (pTau181: β = ‐0.26, p &lt; .005, reinstVTC: β = 0.39, p &lt; .001). Analogous findings were observed with plasma pTau181.ConclusionThese results suggest that APOE ε4 impacts cortical reinstatement, and that this effect may be independent of amyloid burden. These effects of APOE ε4 may be distinct from tau‐mediated effects on episodic memory in human aging.

Prognostic prediction of the longitudinal cognitive trajectory of amyloid‐positive patients with mild dementia

AbstractBackgroundPrediction of longitudinal cognitive decline for patients with mild dementia using baseline characteristics will be useful for designing optimal clinical trials and real‐world patient monitoring. This can be accomplished via machine‐learning models using baseline clinical characteristics. Adding plasma pTau181 and brain region volumes may improve the predictions.MethodThe training cohort (TC) included 905 amyloid‐positive (A+) patients with mild dementia from two clinical trials. The validation cohort (VC) included 230 A+ patients from another clinical trial. Over 85% of these patients had MCI. The longitudinal cognitive decline was defined by the change from baseline in CDR‐SB at months 3, 6, 9, 12, 15, and 18. Plasma pTau181 was measured using Simoa assay in a subset of 159 patients in TC.Structural brain network (SBN) modules and hubs were derived using 207 regional volumetric MRI measures in TC via an algorithm from genomics called “multiscale embedded gene co‐expression network analysis”. A signature for predicting longitudinal cognitive trajectory for each patient was first derived using baseline cognitive assessments and demographics within TC via the Stochastic Gradient Boosting algorithm. The added value of SBNs and plasma pTau181 was then evaluated within this framework. Prediction performance was evaluated in VC via the correlation between predicted versus observed cognitive trajectory.ResultPredictions of the longitudinal cognitive trajectory using baseline cognitive assessments achieved 43.4% and 42.5% correlation with observed values at months 12 and 18 respectively. Key baseline cognitive function predictors were ADAS‐Cog‐14, CDR‐SB, and sub‐scores such as ideational praxis and word recall.Adding baseline SBNs significantly improved the correlation between predicted versus observed cognitive trajectory to 46.3% and 49.7% at months 12 and 18 respectively (p&lt;0.05). Key baseline SBN predictors were middle and inferior temporal, inferior parietal, and superior frontal cortex, along with a module comprising the entorhinal cortex and temporal pole. Adding baseline plasma pTau181 to cognitive assessments yielded similar improvements, but adding both pTau181 and SBNs did not improve the predictions further.ConclusionLongitudinal cognitive decline of A+ patients with mild dementia can be predicted using baseline cognitive assessments. Adding specific structural brain networks or plasma pTau181 significantly improves the predictions.

P049 Actigraphic rest-activity rhythms in older adults ‘at risk’ for dementia: associations with reduced cortical thickness in frontal, temporal and occipital cortices

Abstract Background Rest-activity rhythm disturbance is common in older adults ‘at risk’ for dementia. This may be an early marker of underlying disease pathology and risk of future decline. However, our understanding of how rest-activity rhythm relates to brain integrity remains unclear. Methods This study used vertex-wise analyses to examine the association between nonparametric actigraphy measures and cortical thickness in older adults ‘at risk’ for dementia. Primary measures of interest were intra-daily variability (IV), relative amplitude (RA), inter-daily stability (IS), and average activity during the least active 5-hour period (L5). Results 143 older adults ‘at risk’ for cognitive decline were included (mean age=67.41, SD=7.96). Higher IV was associated with lower cortical thickness in the right cuneus (CWP&amp;lt; 0.001), left middle frontal gyrus (CWP&amp;lt; 0.001) and lateral orbital frontal cortex (CWP=0.004). Higher L5 was linked with cortical thinning in the left superior temporal sulcus (CWP=0.004), superior middle temporal cortex (CWP=0.010) and middle temporal gyrus (CWP=0.013), as well as right inferior parietal lobe (CWP&amp;lt; 0.001). Lower IS was associated with cortical thinning in the left (CWP=0.002) and right (CWP&amp;lt; 0.001) superior frontal gyri, left superior temporal gyrus (CWP=0.043) and left post-central gyrus (CWP=0.033). Conclusions Markers of circadian rhythmicity are associated with reduced cortical thickness in frontal, temporal and occipital cortices in older adults ‘at risk’ for dementia. Future work is still required to delineate whether brain degeneration leads to altered daily rhythms and/or if circadian misalignment contributes to cognitive decline longitudinally.