Temporal Lobe Volume Research Articles

Semiautomatic volumetry of the temporal lobes of the brain and correlation with electroencephalography results in dogs with assumed idiopathic epilepsy.

Lesions causing refractory epilepsy, often associated with temporal lobe epilepsy (TLE), can be undetectable on standard magnetic resonance imaging (MRI) in dogs. Automated brain volumetry, widely used in human medicine, can now be applied in veterinary medicine because of the availability of brain atlases. This study aimed to develop an automatic volumetry method, translate the outcomes into the assessment of temporal lobe volumes in dogs with idiopathic epilepsy, and correlate the results with the electroencephalography (EEG) data of epileptiform discharges (EDs). Thirty-one dogs of various breeds with dominant temporal lobe discharge. Retrospective, observational study. The MRI and EEG examination results of dogs referred for neurological diagnosis data between 2016 and 2021 were retrospectively analyzed. An automated volumetry method was developed, which allowed the evaluation of temporal lobe volumes of the dogs. The asymmetric ratio (AR) was then estimated, and the results were correlated with the EEG EDs. 12/31 (38%; 95% CI: 21.8%-57.8%) dogs had an asymmetric ratio >6%. Among them, reduction in temporal lobe volumes correlated with the side of the EEG EDs in 7 cases. There was no statistical correlation between temporal lobe volume changes and ED location. Preliminary volumetric analysis of the temporal lobes indicates the presence of volume differences between the lobes in some dogs with idiopathic epilepsy. Diagnosis of TLE in dogs based on MRI volumetry in correlation with EEG examination, especially for dogs with drug-resistant epilepsy, can influence the development of new therapeutic options, such as surgery.

Temporal lobe evolution in Hominidae and the origin of human lobe proportions.

Objectives Evolutionary changes in hominin social complexity have been associated with increases in absolute brain size. The temporal lobes are nestled in the middle cranial fossae (MCF) of the skull, the dimensions of which allow estimation of temporal lobe volume (TLV) in extant and fossil taxa. Materials and Methods The main aim of this study is to determine where along the hominid phylogeny, major temporal lobe size transitions occurred. We used computed tomography (CT) scans of crania, 3D photogrammetry data, and laser surface scans of endocranial casts to measure seven MCF metrics in 11 extant anthropoid taxa using multiple regressions to estimate TLV in 5 extant hominids and 10 fossil hominins. Phylogenetic comparative methods mapped temporal lobe size, brain size, and temporal lobe proportions onto phylogenetic trees broadly for Hominidae and specifically for Hominini. Results Extant Homo sapiens were not an outlier in relative brain size, temporal lobe size, or proportions of the temporal lobes, but some proportions within the lobe were uniquely altered. The most notable changes in relative temporal lobe size and proportions saw a decrease in relative temporal lobe size and proportions in the genus Pan compared to other extant great apes and fossil hominins while there was a relative increase in the temporal lobe width and length in Australopithecus-Paranthropus clade compared to the genus Homo and other extant great apes including modern humans. Discussion We do not find support for the social brain, environmental or functional craniology hypotheses alone but think it prudent to consider the implications of cerebral reorganization between the temporal lobes and other regions of the brain within the context of these hypotheses and with future investigation is warranted.

Combined cognitive assessment and automated MRI volumetry improves the diagnostic accuracy of detecting MCI due to Alzheimer's disease

BackgroundMild cognitive impairment (MCI) confers a high annual risk of 10–15 % of conversion to Alzheimer's disease (AD) dementia. MRI atrophy patterns derived from automated ROI analysis, particularly hippocampal subfield volumes, were reported to be useful in diagnosing early clinical stages of Alzheimer's disease. ObjectiveThe aim of the present study was to combine automated ROI MRI morphometry of hippocampal subfield volumes and cortical thickness estimates using FreeSurfer 6.0 with cognitive measures to predict disease progression and time to conversion from MCI to AD dementia. MethodsBaseline (Neuropsychology, MRI) and clinical follow-up data from 62 MCI patients were analysed retrospectively. Individual cortical thickness and volumetric measures were obtained from T1-weighted MRI. Linear discriminant analysis (LDA) of both, cognitive measures and MRI measures (hippocampal subfields, temporal and parietal lobe volumes), were performed to differentiate MCI converters from stable MCI patients. ResultsOut of 62 MCI patients 21 (34 %) converted to AD dementia within a mean follow-up time of 74.7 ± 36.8 months (mean ± SD, range 12 to 130 months). LDA identified temporal lobe atrophy and hippocampal subfield volumes in combination with cognitive measures of verbal memory, verbal fluency and executive functions to correctly classify 71.4.% of MCI subjects converting to AD dementia and 92.7 % with stable MCI. Lower baseline GM volume of the subiculum and the superior temporal gyrus was associated with faster disease progression of MCI converters. ConclusionCombining cognitive assessment with automated ROI MRI morphometry is superior to using a single test in order to distinguish MCI due to AD from non converting MCI patients.

Automated Quantification of Lateral and Medial Temporal Lobe Volumes for Improved Diagnosis of Early Alzheimer’s Disease

Automated Quantification of Lateral and Medial Temporal Lobe Volumes for Improved Diagnosis of Early Alzheimer’s Disease

Association of Gaseous Ambient Air Pollution and Dementia-Related Neuroimaging Markers in the ARIC Cohort, Comparing Exposure Estimation Methods and Confounding by Study Site.

Evidence linking gaseous air pollution to late-life brain health is mixed. We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site. We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide (), nitrogen oxides (), and 8- and 24-h ozone () concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site. Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations. Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, , and and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906.

Cross-Sectional Associations of Peripheral Hearing, Brain Imaging, and Cognitive Performance With Speech-in-Noise Performance: The Aging and Cognitive Health Evaluation in Elders Brain Magnetic Resonance Imaging Ancillary Study.

Population-based evidence in the interrelationships among hearing, brain structure, and cognition is limited. This study aims to investigate the cross-sectional associations of peripheral hearing, brain imaging measures, and cognitive function with speech-in-noise performance among older adults. We studied 602 participants in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) brain magnetic resonance imaging (MRI) ancillary study, including 427 ACHIEVE baseline (2018-2020) participants with hearing loss and 175 Atherosclerosis Risk in Communities Neurocognitive Study Visit 6/7 (2016-2017/2018-2019) participants with normal hearing. Speech-in-noise performance, as outcome of interest, was assessed by the Quick Speech-in-Noise (QuickSIN) test (range: 0-30; higher = better). Predictors of interest included (a) peripheral hearing assessed by pure-tone audiometry; (b) brain imaging measures: structural MRI measures, white matter hyperintensities, and diffusion tensor imaging measures; and (c) cognitive performance assessed by a battery of 10 cognitive tests. All predictors were standardized to z scores. We estimated the differences in QuickSIN associated with every standard deviation (SD) worse in each predictor (peripheral hearing, brain imaging, and cognition) using multivariable-adjusted linear regression, adjusting for demographic variables, lifestyle, and disease factors (Model 1), and, additionally, for other predictors to assess independent associations (Model 2). Participants were aged 70-84 years, 56% female, and 17% Black. Every SD worse in better-ear 4-frequency pure-tone average was associated with worse QuickSIN (-4.89, 95% confidence interval, CI [-5.57, -4.21]) when participants had peripheral hearing loss, independent of other predictors. Smaller temporal lobe volume was associated with worse QuickSIN, but the association was not independent of other predictors (-0.30, 95% CI [-0.86, 0.26]). Every SD worse in global cognitive performance was independently associated with worse QuickSIN (-0.90, 95% CI [-1.30, -0.50]). Peripheral hearing and cognitive performance are independently associated with speech-in-noise performance among dementia-free older adults. The ongoing ACHIEVE trial will elucidate the effect of a hearing intervention that includes amplification and auditory rehabilitation on speech-in-noise understanding in older adults. https://doi.org/10.23641/asha.25733679.

Alterations in Sphenoid Anatomy in Craniosynostosis: Implications for Fronto-Orbital Advancement.

Fronto-orbital advancement involves removal of the fronto-orbital bandeau. Visualization of the saw blade is lost as it passes through the fronto-orbital-sphenoid junction (FOSJ), placing the temporal lobe at risk of injury. We aim to provide a 3D analysis of the space surrounding this osteotomy to differentiate various types of craniosynostoses. Retrospective cohort. Institutional. Thirty patients with isolated unicoronal synostosis, nonsyndromic bicoronal synostosis, metopic synostosis, Apert syndrome, Crouzon syndrome, and Muenke syndrome. CT scans conducted between 2 months to 2 years of age were 3D reconstructed to compare craniometrics against normal controls. Craniometrics. The mean bone thickness of the FOSJ at the level of the supraorbital rim was significantly small for the Apert, unicoronal and bicoronal groups. The mean vertical height of the middle cranial fossa from the lesser sphenoid wing was significantly greater in the unicoronal group. The mean vertical height of the tip of the temporal lobe from the lateral sphenoid ridge was greater in the unicoronal, isolated bicoronal, and Apert groups. The mean corneal protrusion beyond the lateral orbital rim was significantly greater in the Apert and unicoronal groups. The mean horizontal depth of the orbit was smallest in the Apert group. The mean vertical distance between the dacryon and the foramen cecum, and the mean volume of temporal lobe beneath the sphenoid shelf were the largest in the Apert group. Patients with Apert syndrome have the most unfavorable morphology of the anterior and middle cranial fossae.

Brain volume in infants with metopic synostosis: Less white matter volume with an accelerated growth pattern in early life.

Metopic synostosis patients are at risk for neurodevelopmental disorders despite a negligible risk of intracranial hypertension. To gain insight into the underlying pathophysiology of metopic synostosis and associated neurodevelopmental disorders, we aimed to investigate brain volumes of non-syndromic metopic synostosis patients using preoperative MRI brain scans. MRI brain scans were processed with HyperDenseNet to calculate total intracranial volume (TIV), total brain volume (TBV), total grey matter volume (TGMV), total white matter volume (TWMV) and total cerebrospinal fluid volume (TCBFV). We compared global brain volumes of patients with controls corrected for age and sex using linear regression. Lobe-specific grey matter volumes were assessed in secondary analyses. We included 45 metopic synostosis patients and 14 controls (median age at MRI 0.56 years [IQR 0.36] and 1.1 years [IQR 0.47], respectively). We found no significant differences in TIV, TBV, TGMV or TCBFV in patients compared to controls. TWMV was significantly smaller in patients (-62,233 mm3 [95% CI = -96,968; -27,498], Holm-corrected p = 0.004), and raw data show an accelerated growth pattern of white matter in metopic synostosis patients. Grey matter volume analyses per lobe indicated increased cingulate (1378 mm3 [95% CI = 402; 2355]) and temporal grey matter (4747 [95% CI = 178; 9317]) volumes in patients compared to controls. To conclude, we found smaller TWMV with an accelerated white matter growth pattern in metopic synostosis patients, similar to white matter growth patterns seen in autism. TIV, TBV, TGMV and TCBFV were comparable in patients and controls. Secondary analyses suggest larger cingulate and temporal lobe volumes. These findings suggest a generalized intrinsic brain anomaly in the pathophysiology of neurodevelopmental disorders associated with metopic synostosis.

Associations of brain morphology with cortical proteins of cognitive resilience

In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by which RPH3A and CPLX1 are associated with cognitive resilience. Further work is needed to elucidate other mechanisms by which targeting these proteins can circumvent the effects of pathology on individuals at risk for cognitive decline.

MRI evidence for material-specific encoding deficits and mesial-temporal alterations in presurgical frontal lobe epilepsy patients.

Neuroimaging studies reveal frontal lobe (FL) contributions to memory encoding. Accordingly, memory impairments are documented in frontal lobe epilepsy (FLE). Still, little is known about the structural or functional correlates of such impairments. Particularly, material specificity of functional changes in cerebral activity during memory encoding in FLE is unclear. We compared 24 FLE patients (15 right-sided) undergoing presurgical evaluation with 30 healthy controls on a memory fMRI-paradigm of learning scenes, faces, and words followed by an out-of-scanner recognition task as well as regarding their mesial temporal lobe (mTL) volumes. We also addressed effects of FLE lateralization and performance level (normal vs. low). FLE patients had poorer memory performance and larger left hippocampal volumes than controls. Volume increase seemed, however, irrelevant or even dysfunctional for memory performance. Further, functional changes in FLE patients were right-sided for scenes and faces and bilateral for words. In detail, during face encoding, FLE patients had, regardless of their performance level, decreased mTL activation, while during scene and word encoding only low performing FLE patients had decreased mTL along with decreased FL activation. Intact verbal memory performance was associated with higher right frontal activation in FLE patients but not in controls. Pharmacoresistant FLE has a distinct functional and structural impact on the mTL. Effects vary with the encoded material and patients' performance levels. Thus, in addition to the direct effect of the FL, memory impairment in FLE is presumably to a large part due to functional mTL changes triggered by disrupted FL networks. Frontal lobe epilepsy (FLE) patients may suffer from memory impairment. Therefore, we asked patients to perform a memory task while their brain was scanned by MRI in order to investigate possible changes in brain activation during learning. FLE patients showed changes in brain activation during learning and also structural changes in the mesial temporal lobe, which is a brain region especially relevant for learning but not the origin of the seizures in FLE. We conclude that FLE leads to widespread changes that contribute to FLE patients' memory impairment.

Analysis of Major Lobe Volume and Asymmetry of the Brain by Gender: A vol2Brain Study

Objective: In recent years, with the use of three-dimensional (3D) software tools, volumetric measurements of brain morphometry have gained importance. In this study, we aim to investigate the ratio of the volumes of the major structures of the brain (frontal, parietal, temporal, and occipital lobes) to the volume of the intracranial cavity (ICC) and the change of asymmetry according to gender, using web-based vol2Brain, which is one of the current and automatic software tools. Materials and Methods: 3D-T1-weighted magnetic resonance images of 80 healthy individuals (43 females and 37 males) of both genders were included in our study. The volumes of major brain lobes were calculated with the vol2Brain pipeline software tool and their ratio to ICC was compared by gender. Results: Males ICC volume, frontal, parietal, temporal, and occipital lobe total volume values were statistically higher than females (P < 0.05). Similarly, the right and left volume values of male were higher than those of female in all measurements. However, when the frontal, parietal, temporal, and occipital lobe volumes of male and female were proportion to the ICC volume, there was no statistically significant difference (P > 0.05). There was no statistically significant difference in the asymmetry results of these cortical structures examined in both genders (P > 0.05). Conclusions: Although the male brain is known to be large, no difference was found between the male and female brains as a result of the ratio. Considering the asymmetry values, frontal, parietal, occipital, and temporal lobe volume asymmetry values did not differ statistically in both genders.

Correlation between white matter hyperintensity and delusional symptoms in Alzheimer’s disease

BackgroundPatients with Alzheimer’s disease (AD) often exhibit neuropsychiatric symptoms (NPS), particularly delusions. Previous studies have shown an association between white matter hyperintensities (WMH) and specific NPS. This study aims to explore the relationship between WMH volume and delusions in AD patients by comparing the WMH volumes of delusional and non-delusional subgroups.Methods80 AD patients were divided into a delusion group (n = 36) and a non-delusion group (n = 44) based on the Neuropsychiatric Inventory (NPI). The brain cortical volume and WMH volume were quantitatively calculated for all 80 patients, including total WMH volume, periventricular WMH (PVWMH) volume, deep WMH volume, as well as bilateral frontal lobe, temporal lobe, parietal lobe, and occipital lobe WMH volumes. Firstly, we compared the differences in WMH volumes between the delusion group and non-delusion group. Then, within the delusion group, we further categorized patients based on severity scores of their delusional symptoms into mild (1 point), moderate (2 points), or severe groups (3 points). We compared the WMH volumes among these three groups to investigate the role of WMH volume in delusional symptoms.ResultsThere was a significant difference in left occipital lobe WMH volume between the delusion group and non-delusion group(P < 0.05). Within the delusion group itself, there were significant differences in overall WMH volume as well as PVWMH volume among patients with mild or severe levels of delusions(P < 0.05).ConclusionLeft occipital lobe WMH volume may be associated with the occurrence of delusional AD patients, and the total volume of whole-brain WMH and PVWMH volume may affect the degree of severity of delusional symptoms.

Relationship of structural and functional visual biomarkers with measures of amyloid, tau, and neurodegeneration across the AD continuum

AbstractBackgroundThe eye often reflects changes seen in the brain in neurodegenerative diseases. This study sought to examine the relationship of contrast sensitivity measured using frequency doubling technology (FDT) and retinal thickness measured using optical coherence tomography (OCT) with temporal lobe neurodegeneration, cerebral tau deposition, and mean plasma ptau181 in older adults along the Alzheimer’s disease (AD) continuum.MethodParticipants included 28 individuals with subjective cognitive decline (SCD), 18 mild cognitive impairment (MCI), 4 with AD, and 30 age‐matched cognitive normal (CN) from the Indiana Memory and Aging Study at the Indiana ADRC. Participants were excluded from the study if they had significant eye disease determined to interfere with OCT, FDT, non‐AD dementia, or exclusion for MRI or PET. Mean deviation (MD) and pattern standard deviation (PSD) from FDT were used as measures of contrast sensitivity. OCT scans from each eye to measure retinal thickness in the retinal nerve fiber layer (RNFL) and macula. MRI scans were processed using Freesurfer v6 to measure medial (MTL) and lateral temporal lobe (LTL) volumes. LTL SUVR values were extracted from [18F]flortaucipir PET scans. Plasma ptau 181 was measured using a SIMOA assay. Finally, the association between contrast sensitivity, average RNFL thickness, macular volumes with temporal lobe volumes, LTL tau, and mean plasma ptau181 was assessed using a partial Pearson correlation, covaried for age, sex, and diagnosis. p&lt;0.05 was considered significant.ResultRNFL thickness was decreased in patients with AD. Hippocampal volume correlated with RNFL thickness and macular volume in both eyes and with PSD in the left eye. The inferior temporal volume correlated with MD in both eyes, while mean plasma ptau181 with PSD in both eyes. Finally, lateral temporal lobe tau was correlated with the inner retinal layers of ganglion cell layer plus inner plexiform layer thickness.ConclusionContrast sensitivity correlates with temporal lobe volumes and mean plasma ptau181. RNFL thinning and macular volumes are associated with hippocampal atrophy, and inner retinal nuclear layers correlate with lateral temporal tau. Imaging of the eye may represent a useful biomarker to screen patients at risk for AD prior to more invasive and prolonged testing.

MRI CHANGES FOLLOWING TREATMENT OF GLP‐1 ANALOGUE, LIRAGLUTIDE IN ALZHEIMER’S DISEASE

AbstractBackgroundPreclinical evidence in transgenic models of Alzheimer’s disease (AD) suggests that liraglutide, a GLP1 analogue, exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and reducing insulin resistance, and increasing the proliferation of neuronal progenitor cells. ELAD is a 12‐month, multi‐centre, randomised, double‐blind, placebo‐controlled, phase IIb trial of liraglutide in participants with mild to moderate AD conducted at 24 centres in the UK.MethodAs a part of this study, a total of 204 Alzheimer’s participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. All subjects underwent volumetric MRI scans at baseline and during follow up. Volumetric changes from baseline to follow up in MRI scans were evaluated using both regional volume analysis and voxel based morphometric analysisResultMRI analysis demonstrated that temporal lobe volume, total grey matter volume and frontoparietal volume change was lower in liraglutide treated patients compared to the placebo group. Voxel based morphometry (VBM) analysis demonstrated that liraglutide‐treated participants showed a slower reduction in whole cortical grey matter, frontal, temporal and parietal lobe volume in participants treated with liraglutide compared to placebo.ConclusionIn the ELAD study, participants with mild to moderate AD who received liraglutide had slower reduction in MRI volume and cognition compared to the placebo demonstrating a potential benefit of liraglutide in the treatment of Alzheimer’s disease. These findings highlight the potential of GLP‐1 analogues in the treatment of Alzheimer’s disease

Larger hippocampal and temporal lobe volume may associate with early rapid forgetting in cognitively healthy individuals with a predisposition to Alzheimer’s disease

AbstractBackgroundGrowing need exists to link volumetric brain analysis to functional cognitive performance in early prediction of Alzheimer’s disease.MethodIn cognitively healthy older adults (N = 40; M age = 71.7±7.7 years), we established amyloid/tau ratios from cerebrospinal fluid, thus finding a small group with pathological amyloid/tau ratios (PAT, n = 11) and normal ratio (NAT, n = 29). Approximately 40% of the PAT group were expected to convert to mild cognitive impairment within 4 years. It was hypothesized that reduced performance on the California Verbal Learning Test‐II (CVLT‐II) Short Delay Free (SDFR) and Cued Recall (SDCR) task would be associated with smaller hippocampal and temporal lobe volume (obtained via NeuroQuant).ResultHippocampal total, left, and right percentiles were found to be negatively associated with SDFR in the PAT group, r(38) = ‐.67*, ‐.66*, and ‐.63*, but not in the NAT group, r(38) = ‐.21, ‐.04, and ‐.35, such that a larger hippocampus was associated with fewer remembered words after a short delay on a list learning task in those with pathological amyloid/tau ratios. Temporal lobe volume was also found to be negatively associated with SDFR and SDCR in the PAT group, r(38) = ‐.67* and ‐.69*, but not in the NAT group, r(38) = ‐.36 and ‐.34, such that a larger temporal lobe was associated with fewer remembered words after a short delay on a list learning task (even when cued) in those with smaller amyloid/tau ratios. Two hierarchical multiple regression analyses, one including amyloid/tau ratio and the other including amyloid only, found that age and sex associate with ∼20.4% variance of the performance on the CVLT‐II SDFR task while temporal lobe volume increased associative value by 16.1% in the former [F (1, 35) = 8.871, p &lt; .05] and by 15.4% in the latter [F (1, 35) = 8.430, p &lt; .05].ConclusionOur findings suggest there may be early compensation in brain structures among cognitively healthy individuals whose CSF biomarker suggest increased risk for the development of symptomatic Alzheimer’s disease, such that hippocampi and temporal lobes increase in size during early pre‐Alzheimer’s stages despite reduced performance on memory tasks.

Utility of accessible neuroimaging markers of cerebrovascular disease in identifying cerebral amyloidosis across the Alzheimer’s disease spectrum

AbstractBackgroundAlzheimer’s disease (AD) is defined by the presence of cognitive impairment and cerebral amyloidosis and is associated with several cerebrovascular disease (CVD) risk factors including age, apolipoprotein‐E ε4 (APOE‐ε4) genotype, hypertension, diabetes and hyperlipidemia. Despite this association, the clinical utility of individual CVD biomarkers in screening for AD pathology is understudied. Therefore, we sought to examine the relationship between cerebral amyloidosis and magnetic resonance imaging (MRI)‐based CVD measures, including cerebral microbleeds, ischemic infarction, and white matter hyperintensities (WMH). We hypothesized that CVD biomarker burden would be positively associated with amyloidosis. Given recent studies have shown plasma phospho‐tau181 (P‐tau181) is a promising early biomarker of amyloidosis, we further hypothesized that combining P‐tau181 with CVD biomarkers would predict amyloid status in cognitively unimpaired and impaired persons.MethodParticipant data were extracted from the Alzheimer’s Disease Neuroimaging Initiative database (N = 1,430). Volumetric data (WMH volume [WMHv], medial temporal lobe volume [MTLv]) were normalized and log‐transformed. Adjusted odds ratio (OR) was calculated using logistic regression with dichotomized amyloid‐PET status as the outcome. Area under the curve (AUC) was compared by the likelihood ratio test.ResultAfter adjustment for age, sex, APOE‐ε4 status, MTLv, cognition (MoCA), and other CVD biomarkers of interest, we found that WMHv alone was significantly associated with amyloidosis in both cognitively impaired (OR = 1.21) and unimpaired (OR = 1.25) persons. We then developed an accessible diagnostic model incorporating WMHv, significant covariates and plasma P‐tau181. Addition of P‐tau181 to the model improved diagnostic accuracy in cognitively impaired persons (AUC = 0.85 to 0.87, p &lt; 0.001), and did not attenuate the relationship between WMHv and amyloidosis.ConclusionWe newly identify WMH, but not other CVD lesions, as predictive of amyloidosis in both preclinical and symptomatic AD. The current study adds to the literature regarding which CVD biomarkers are most predictive of AD pathology. Measurement of WMH alongside P‐tau181 and other biomarkers may produce an accessible screening algorithm for AD. Study generalizability is limited by ascertainment bias and lack of diversity. Future research will compare the performance of WMH to standard AD biomarkers in a more diverse, community‐based sample.

58 Right Anterior Temporal Lobe Atrophy is Associated with Informant-Reported Socioemotional Dysfunction in Patients with Frontotemporal and Early Onset Alzheimer's Dementia

Objective:Abnormalities in social and emotional behavior are the major diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed their behavioral disturbances to disease in mesial prefrontal and related networks, such as the salience network. This study examined the main neural correlates of informant-reported socioemotional dysfunction among patients with bvFTD compared to those with early-onset (before age 65) Alzheimer's Disease (EOAD).Participants and Methods:Participants included 13 patients with bvFTD and their caregivers and 18 patients with EOAD and their caregivers. The caregivers consisted of a spouse, family member, or other informant who resided with the patient. They completed the informant-based Socioemotional Dysfunction Scale (SDS), a 40-item scale which rates common disturbances in social and emotional behavior on a five-point Likert scale (1-5). The patients underwent magnetic resonance imaging (MRI) with tensor-based morphometry (TBM) analysis of the 3D T1-weighted MRI scans. Computations of mean Jacobian values within select regions of interest (ROIs) in frontal and temporal lobes generated numerical summaries of regional volumes, and voxel-wise regressions created 3D statistical maps of the association between tissue volume and SDS total scores. Statistical analyses included independent samples t-tests group differences in ROIs and SDS scores, Pearson correlations between SDS scores and brain volumes, and multiple regression of ROIs with SDS scores and group as predictor variables.Results:Compared to the EOAD group, the bvFTD group had significantly higher SDS scores (p &lt; .001; d = 2.24), smaller frontal lobe volumes (specifically dorsolateral-prefrontal cortex, p = .003; d = 1.24), and larger temporal lobe volumes (specifically hippocampus, p = .014; d = 0.979). Within the bvFTD group, higher SDS scores were associated with a smaller right anterior temporal lobe (ATL; p = .005; r = -.729), especially the lateral ATLs (p = .002; r = -.776), and a smaller bilateral orbitofrontal cortex (OFC; p = .016; r = -.650). In contrast, within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex (p = .030; r = .542). In the entire sample (both bvFTD and EOAD), higher SDS scores was associated with a smaller lateral ATL volumes (p = .019; r = -.431). Regression analyses confirmed that SDS score predicted lateral ATL volume (p = .041; b = -.262) after controlling for diagnosis (p &lt; .001; b = -.692).Conclusions:These findings are consistent with greater socioemotional dysfunction, smaller frontal, and larger mesial temporal regions in bvFTD, when compared to EOAD. The findings, however, suggest that positively disturbed socioemotional behavior in bvFTD, as reported by caregivers, results from involvement of the right temporal lobe and the lateral temporal region, with further contribution from disease in OFC. The association of SDS scores and ATL volume across diagnostic groups suggests that this region is instrumental in socioemotional functioning and that the SDS may have diagnostic value in distinguishing the "right-temporal variant" of bvFTD.

Artificial-intelligence-based MRI brain volumetry in patients with essential tremor and tremor-dominant Parkinson's disease.

Essential tremor and Parkinson's disease patients may present with various tremor types. Overlapping tremor features can be challenging to diagnosis and misdiagnosis is common. Although underlying neurodegenerative mechanisms are suggested, neuroimaging studies arrived at controversial results and often the different tremor types were not considered. We investigated whether different tremor types displayed distinct structural brain features. Structural MRI of 61 patients with essential tremor and 29 with tremor-dominant Parkinson's disease was analysed using a fully automated artificial-intelligence-based brain volumetry to compare volumes of several cortical and subcortical regions. Furthermore, essential tremor subgroups with and without rest tremor or more pronounced postural and kinetic tremor were investigated. Deviations from an internal reference collective of age- and sex-adjusted healthy controls and volumetric differences between groups were examined; regression analysis was used to determine the contribution of disease-related factors on volumetric measurements. Compared with healthy controls, essential tremor and tremor-dominant Parkinson's disease patients displayed deviations in the occipital lobes, hippocampus, putamen, pallidum and mesencephalon while essential tremor patients exhibited decreased volumes within the nucleus caudatus and thalamus. Analysis of covariance revealed similar volumetric patterns in both diseases. Essential tremor patients without rest tremor showed a significant atrophy within the thalamus compared to tremor-dominant Parkinson's disease and atrophy of the mesencephalon and putamen were found in both subgroups compared to essential tremor with rest tremor. Disease-related factors contribute to volumes of occipital lobes in both diseases and to volumes of temporal lobes in essential tremor and the putamen in Parkinson's disease. Fully automated artificial-intelligence-based volumetry provides a fast and rater-independent method to investigate brain volumes in different neurological disorders and allows comparisons with an internal reference collective. Our results indicate that essential tremor and tremor-dominant Parkinson's disease share structural changes, indicative of neurodegenerative mechanisms, particularly of the basal-ganglia-thalamocortical circuitry. A discriminating, possibly disease-specific involvement of the thalamus was found in essential tremor patients without rest tremor and the mesencephalon and putamen in tremor-dominant Parkinson's disease and essential tremor without rest tremor.

Volumetric brain correlates of gait associated with cognitive decline in community-dwelling older adults.

To determine the extent to which the regional brain volumes associated with slow gait speed can inform subsequent cognitive decline in older adults from the Rush Memory and Aging Project. We utilized deformation-based morphometry (DBM) in a whole-brain exploratory approach to identify the regional brain volumes associated with gait speed assessed over a short distance during an in-home assessment. We created deformation scores to summarize the gait-associated regions and entered the scores into a series of longitudinal mixed effects models to determine the extent to which deformation predicted change in cognition over time, controlling for associations between gait and cognition. In 438 older adults (81 ± 7; 76% female), DBM revealed that slower gait speed was associated with smaller volumes across frontal white matter, temporal grey matter, and subcortical areas and larger volumes in the ventricles during the same testing cycle. When a subset was followed over multiple (5 ± 2) years, slower gait speed was also associated with annual declines in global cognition, executive functioning, and memory abilities. Several of the gait-related brain structures were associated with these declines in cognition; however, larger ventricles and smaller medial temporal lobe volumes proved most robust and attenuated the association between slow gait and cognitive decline. Regional brain volumes in the ventricles and temporal lobe associated with both slow gait speed and faster cognitive decline have potential to improve risk stratification for cognitive decline in older adults.

Disturbed sleep is associated with reduced verbal episodic memory and entorhinal cortex volume in younger middle-aged women with risk-reducing early ovarian removal.

Women with early ovarian removal (<48 years) have an elevated risk for both late-life Alzheimer's disease (AD) and insomnia, a modifiable risk factor. In early midlife, they also show reduced verbal episodic memory and hippocampal volume. Whether these reductions correlate with a sleep phenotype consistent with insomnia risk remains unexplored. We recruited thirty-one younger middleaged women with risk-reducing early bilateral salpingo-oophorectomy (BSO), fifteen of whom were taking estradiol-based hormone replacement therapy (BSO+ERT) and sixteen who were not (BSO). Fourteen age-matched premenopausal (AMC) and seventeen spontaneously peri-postmenopausal (SM) women who were ~10y older and not taking ERT were also enrolled. Overnight polysomnography recordings were collected at participants' home across multiple nights (M=2.38 SEM=0.19), along with subjective sleep quality and hot flash ratings. In addition to group comparisons on sleep measures, associations with verbal episodic memory and medial temporal lobe volume were assessed. Increased sleep latency and decreased sleep efficiency were observed on polysomnography recordings of those not taking ERT, consistent with insomnia symptoms. This phenotype was also observed in the older women in SM, implicating ovarian hormone loss. Further, sleep latency was associated with more forgetting on the paragraph recall task, previously shown to be altered in women with early BSO. Both increased sleep latency and reduced sleep efficiency were associated with smaller anterolateral entorhinal cortex volume. Together, these findings confirm an association between ovarian hormone loss and insomnia symptoms, and importantly, identify an younger onset age in women with early ovarian removal, which may contribute to poorer cognitive and brain outcomes in these women.