Temporal Lobe Volume Research Articles

Ultra-high-field 7T MRI reveals changes in human medial temporal lobe volume in female adults during menstrual cycle

Ovarian hormones have substantial effects on the brain, and early menopause has been associated with increased risk of accelerated brain aging and dementia later in life. However, the impact of ovarian hormone fluctuations on brain structure earlier in life is less understood. Here we show that ovarian hormone fluctuations shape structural brain plasticity during the reproductive years. We use longitudinal ultra-high field neuroimaging across the menstrual cycle to map the morphology of medial temporal lobe subregions in 27 participants. Controlling for water content and blood flow, our findings reveal positive associations between estradiol and parahippocampal cortex volume, progesterone and subiculum and perirhinal area 35 volumes, and an estradiol*progesterone interaction with CA1 volume. This research offers a blueprint for future studies on the shared dynamics of the brain and ovarian function and a fundamental stepping stone towards developing sex-specific strategies to improve brain health and mental health.

The Lyman Normal Tissue Complication Probability Model and Risk Prediction for Temporal Lobe Injury after Re-Irradiation in Patients with Recurrent Nasopharyngeal Carcinoma

The risk of temporal lobe injury (TLI) in recurrent nasopharyngeal carcinoma (rNPC) patients with intensity-modulated radiation therapy (IMRT) is high. We aimed to construct the normal tissue complication probability (NTCP) model for TLI of rNPC and establish a risk predictive model. We retrospectively analyzed 103 patients with rNPC who had received two courses of IMRT in our institution. The 206 temporal lobes (TLs) of these patients were randomly divided into a training (n = 144) and validation group (n = 62). We determined the mean value of the following parameters to construct the Lyman NTCP model: TD50(1) (the dose with a 50% probability of complications to an organ when all volumes are irradiated), m [steepness of the dose-response at TD50(1)], and n (the parameter related to volume effect). The most predictive dosimetric parameter and clinical variables were integrated in Cox proportional hazards models. A nomogram was developed for predicting risk of TLs. The parameters of the fitted NTCP model were TD50(1) = 107.84 Gy (95% confidence interval (CI), [97.15, 118.54]), m = 0.16 (95% CI, [0.14, 0.19]), and n = 0.04 (95% CI, [0.01, 0.06]). The cumulative dose delivered to 0.1 cm3 of temporal lobe volume (D0.1cc-c) was the most predictive dosimetric parameter for TLI. The Kaplan-Meier curves showed a significant difference in 2-year TLI-free survival among different risk groups according to the total score of nomograms. The TD50(1) of TLI in patients with rNPC is 107.84 Gy in Lyman NTCP model. The nomogram model can accurately predict the risk of TLI for individual.

Dairy products and brain structure in French older adults.

Among food groups with putative benefits for brain structures, dairy products (DP) have been poorly studied. The sample included participants without dementia from the ancillary brain imaging study of the Three-City cohort who were aged 65+ years, had their DP intake assessed with a FFQ at baseline and underwent an anatomical scan 3 years (n 343) or 9 years (n 195) after completing the dietary survey. The frequencies of consumption of total DP, milk and cheese were not associated with brain structure. Compared with the lowest frequency, the highest frequency of fresh DP (F-DP) consumption (< 0·5 v. > 1·5 times/d) was significantly associated with a lower medial temporal lobe volume (MTLV) (β = -1·09 cm3, 95 % CI - 1·83, -0·36) 9 years later. In this population-based study of older adults, the consumption of F-DP more than 1·5 times/d was associated with a lower MTLV, which is considered an early biomarker of Alzheimer's disease, 9 years later. This original study should be replicated in different settings before conclusions are drawn.

P11.01.A BASELINE TOTAL BRAIN VOLUME PREDICTS FOR POORER QUALITY OF LIFE AND REDUCED OVERALL SURVIVAL AFTER CRANIAL RADIOTHERAPY IN OLDER PATIENTS WITH GLIOBLASTOMA (GBM): RESULTS FROM THE PROSPECTIVE BRITER STUDY

Abstract BACKGROUND GBM incidence peaks in the 7th and 8th decades, with median life expectancy of 3-6 months. Treatment decisions finely balance benefit to side-effects and worsening quality of life (QoL). Short-course partial brain radiotherapy, +/- chemotherapy, extends survival compared to supportive care but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. We aimed to consider putative MRI markers of brain resilience and their relationship to change in QoL amongst older patients being treated for GBM with cranial radiotherapy. MATERIAL AND METHODS BRITER, a prospective multicentre observational trial, recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for: relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)), contralateral medial temporal lobe volume, number and volume of T1 white matter hypointensities, and Fazekas' scale of white matter change. Radiotherapy treatment volumes were obtained from planning software. RESULTS 126 patients were enrolled from 12 UK centres; mean age 72 years (range 65-83); 67% men, 33% women. 4% had a radiological diagnosis, 19% biopsy and 77% had debulking surgery. 21% received palliative radiotherapy alone (25% 30Gy/6#, 75% 40Gy/15#), 79% received radiotherapy with concurrent TMZ (47% 40Gy/15#, 53% 60Gy/30#). Median OS was 11.3 months. 56 participants completed all MRI sequences and QoL data points. After accounting for age, sex, treatment and baseline MoCA score, there was a significant relationship between baseline CSF:TIV ratio and change in QoL score. For each unit point of increase in CSF:TIV ratio, there was a corresponding decrease in EORTC QLC C30 QoL score by a factor of 1.27 (coefficient -1.27, 95% CI -3.24 to -0.19 p=0.02). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV ratio was related to risk of non-attendance (OR 1.35, 95% CI 1.01-1.80, p=0.04). Cox regression models were fitted for time to death in 88 participants who had analysable baseline MRI sequences. Baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19-1.66, p&amp;lt;0.001). CONCLUSION This unique prospective study indicates that baseline imaging parameters can predict the impact of cranial radiotherapy on QoL and OS. Due to frailty, there was a significant attrition rate in data return. 29% of participants were too unwell by 8 weeks post treatment to attend hospital, also predicted by baseline imaging. These results promote and enable discussion of individualised treatment options with older patients with GBM, differentiating those who are likely to suffer reduced QoL and short survival rather than benefit from radiotherapy

Cortical and subcortical morphometric changes and their relation to cognitive impairment in isolated REM sleep behavior disorder.

To date, very few studies have focused on structural changes and their association with cognitive performance in isolated REM sleep behaviour disorder (iRBD). Moreover, the results of these studies are inconclusive. This study aims to evaluate differences in the associations between brain morphology and cognitive tests in iRBD and healthy controls. Sixty-three patients with iRBD and thirty-six controls underwent MRI with a 3T scanner. The cognitive performance was assessed by a comprehensive neuropsychological battery. Based on performance, the iRBD group was divided into two subgroups with (iRBD-MCI) and without mild cognitive impairment (iRBD-NC). The high-resolution T1-weighted images were analysed using an automated atlas segmentation tool, voxel-based (VBM) and deformation-based (DBM) morphometry to identify between-group differences and correlations with cognitive performance. VBM, DBM and the comparison of ROI volumes yielded no significant differences between iRBD and controls. In the iRBD group, significant correlations in VBM were found between several cortical and subcortical structures primarily located in the temporal, parietal, occipital lobe, cerebellum, and basal ganglia and three cognitive tests assessing psychomotor speed and one memory test. Between-group analysis of cognition revealed a significant difference between iRBD-MCI and iRBD-NC in tests including a processing speed component. iRBD shows deficits in several cognitive tests that correlate with morphological changes, the most prominent of which is in psychomotor speed and visual attention as measured by the TMT-A and associated with the volume of striatum, insula, cerebellum, temporal lobe, pallidum and amygdala.

Alzheimer’s pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome

BackgroundTraumatic encephalopathy syndrome (TES) is a clinical phenotype sensitive but non-specific to underlying chronic traumatic encephalopathy (CTE) neuropathology. However, cognitive symptoms of TES overlap with Alzheimer’s disease (AD), and features of AD pathology like beta-amyloid (Aβ) plaques often co-occur with CTE, making clinical-to-pathological conclusions of TES diagnoses challenging. We investigated how Alzheimer’s neuropathological changes associated with cognition, brain volume, and plasma biomarkers in patients with repetitive head impacts (RHI)/TES, clinical AD, or typically aging controls.MethodsWe studied 154 participants including 33 with RHI/TES (age 61.5 ± 11.5, 100% male, 11/33 Aβ[ +]), 62 with AD and no known prior RHI (age 67.1 ± 10.2, 48% male, 62/62 Aβ[ +]), and 59 healthy controls without RHI (HC; age 73.0 ± 6.2, 40% male, 0/59 Aβ[ +]). Patients completed neuropsychological testing (memory, executive functioning, language, visuospatial) and structural MRI (voxel-based morphometry analysis), and provided plasma samples analyzed for GFAP, NfL, IL-6, IFN-γ, and YKL-40. For cognition and plasma biomarkers, patients with RHI/TES were stratified as Aβ[ +] or Aβ[ −] and compared to each other plus the AD and HC groups (ANCOVA adjusting for age and sex). Differences with at least a medium effect size (Cohen’s d > 0.50) were interpreted as potentially meaningful.ResultsCognitively, within the TES group, Aβ[ +] RHI/TES performed worse than Aβ[-] RHI/TES on visuospatial (p = .04, d = 0.86) and memory testing (p = .07, d = 0.74). Comparing voxel-wise brain volume, both Aβ[ +] and Aβ[ −] RHI/TES had lower medial and anterior temporal lobe volume than HC and did not significantly differ from AD. Comparing plasma biomarkers, Aβ[ +] RHI/TES had higher plasma GFAP than HC (p = .01, d = 0.88) and did not significantly differ from AD. Conversely, Aβ[ −] RHI/TES had higher NfL than HC (p = .004, d = 0.93) and higher IL-6 than all other groups (p’s ≤ .004, d’s > 1.0).ConclusionsPresence of Alzheimer’s pathology in patients with RHI/TES is associated with altered cognitive and biomarker profiles. Patients with RHI/TES and positive Aβ-PET have cognitive and plasma biomarker changes that are more like patients with AD than patients with Aβ[ −] RHI/TES. Measuring well-validated Alzheimer’s biomarkers in patients with RHI/TES could improve interpretation of research findings and heighten precision in clinical management.

Magnetic resonance morphometry of the brain volume, medial temporal lobes and hippocampus in middle-aged patients with premild cognitive decline

Currently, instrumental brain imaging plays a significant role in the examination of patients with cognitive impairment. It is important for diagnostic process, prognosis of the course of neurodegenerative, cerebrovascular and other diseases, clarification of the role of individual brain structures and systems in the development of cognitive and other neuropsychiatric disorders.The purpose of the study was to analyze the volumes of the medial temporal lobes (MTL), hippocampus and brain volume in middle-aged patients with pre-mild cognitive decline.Material and methods. 38 patients (33 women, 5 men) of middle age (60.77 ± 9.4 years) were examined. Patients were divided into two groups: with subjective cognitive decline (SCD) – 15 patients, aged 53.5 ± 6.94 years and subtle cognitive decline (StCD) – 23 people aged 63.35 ± 8.64 years (groups statistically did not differ in age). All patients underwent a neuropsychological examination with an assessment of the cognitive sphere, magnetic resonance imaging of the brain, including the assessment of the presence and degree of microangiopathy (MAP), morphometry of the medial temporal lobes, hippocampus, brain volume and a study for the presence of the allele of the apolyprotein E gene (ApoE4).Results. A decrease in the average and total hippocampal volume was found in patients with StCD compared to patients with SCD. Also, MAP was significantly more common in patients with StCD. There were no differences in the degree of MTL atrophy. A decrease in the volume of the left hippocampus was revealed in patients with aggravated heredity for dementia. The average and total volume of the hippocampus is reduced in carriers of the ApoE4 allele of the apolyprotein gene. Correlation analysis showed the relationship between the average volume of the hippocampus and the volume of the brain.

340-OR: ADA Presidents' Select Abstract: Structural Neuroimaging and Cognitive Function in Long-Duration Type 1 Diabetes

Cognitive decline is an increasingly important complication in people with type 1 diabetes (T1D) as they age. We previously reported that compared with nondiabetic people, those with long-duration T1D have impaired cognitive function, similar to people with type 2 diabetes. To characterize factors associated with cognitive decline in people with T1D, 52 participants of the Joslin Medalist Study (“Medalists”) with T1D≥50 years, and 20 age-matched nondiabetic controls, underwent clinical evaluation, cognitive assessments, and neuroimaging (Alzheimer Disease Neuroimaging Initiative-3 protocol). Compared to controls, Medalists had 49.4 (±21.9) cm3 (p=0.03) lower total brain volume, and 2.7 (±0.8) cm3, 3.0 (±1.5) cm3 and 3.1 (±1.5) cm3 lower volumes (p&amp;lt;0.05), respectively, in the deep gray matter region (thalamus, putamen, caudate and globus pallidus), the Alzheimer disease signature region (hippocampus, parahippocampus, entorhinal cortex, inferior parietal lobule, precuneus and cuneus), and the occipital lobe. No significant differences were observed in frontal, temporal, or parietal lobe volumes. In assessing small vessel disease, the number of white matter hyperintensities (WMHs) or microvascular hemorrhages did not differ between Medalists and controls, nor did regional cerebral blood flow measures (via arterial spin labeling). Among Medalists, reduced total and all regional brain volumes were associated (p&amp;lt;0.05) with worse motor skills, female sex, lower education status, increased age, and longer diabetes duration. Increased WMHs were associated with worse renal function and higher coronary artery calcification scores. Volumes did not associate with other cognitive domains (recall, working memory, or executive function). These findings suggest that cognitive decline in people with long-duration T1D is related mainly to abnormalities in parenchymal CNS rather than neurovascular changes. Definitive confirmation of this finding by brain histopathology is underway. Disclosure H. Shah: None. M. Desalvo: None. A. Haidar: None. S. Jangolla: None. M. Yu: None. J. Gauthier: None. N.A. Ziemniak: None. I. Wu: None. T. Billah: None. L. Ning: None. A. Adam: None. Y. Rathi: None. G.L. King: Research Support; Janssen Research &amp; Development, LLC. Funding National Institute of Diabetes and Digestive and Kidney Diseases (3P30DK036836-34S1); Thomas J. Beatson, Jr. Foundation

Temporal lobe evolution in extant and extinct Cercopithecoidea

Changes to the environmental landscapes from the Eocene to Holocene have influenced the evolution of Cercopithecoidea from arboreal origins in wet, forested regions in the Early Oligocene Fayum to semi-terrestrial lifestyles in drier Neogene landscapes and social systems of larger group living. These eco-behavioural transitions likely accompanied changes in behaviour, brain function, and associated skull morphology. The temporal lobe of the brain, an association cortex, is in close proximity to the middle cranial fossa (MCF) allowing prediction of temporal lobe volume (TLV) and investigation of cerebral reorganisation. We used micro-computed tomography (µCT) cranial scans (n = 135) generated into 3D virtual crania with seven MCF metrics predicting TLV from a multiple regression of 11 extant anthropoid taxa. We studied eight extinct taxa Proteopithecus sylviae and Catopithecus browni from the Late Eocene, Early Oligocene Apidium phiomense, Parapithecus grangeri and Aegyptopithecus zeuxis, Middle Miocene Victoriapithecus macinnesi, Pliocene Dinopithecus ingens, Pleistocene Papio angusticeps, and extant cercopithecines Cercocebus atys, Macaca mulatta and Papio anubis. PGLS regressions examined relative TLV to brain size between extinct and extant taxa. We tested differences in slopes and intercepts between extinct and extant cercopithecoids with statistically significant differences in slopes but not the intercepts, with stem-anthropoids having relative smaller TLV for brain size compared to extant cercopithecoids. Potential drivers for temporal lobe evolution include paleoenvironmental shifts from Eocene tropical rainforests to Plio-Pleistocene savannas. Socio-behavioural implications include change from arboreal to semi-terrestrial lifestyles, higher visual acuity, larger group sizes and greater cognitive complexity.

Early Detection of Dementia using Risk Classification in MCI: Outcomes of Shanghai Mild Cognitive Impairment Cohort Study.

The purpose of this study is to identify the risk factors and risk classification associated with the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia to facilitate early intervention and the design of clinical trials for AD. The study comprised a prospective cohort study of 400 subjects with MCI who had annual follow-ups for 3 years. During an average follow-up period of 3.5 years, 109 subjects were diagnosed with all cause of dementia, of whom 104 subjects converted to Alzheimer's dementia and 5 subjects converted to other types of dementia. The cumulative conversion rate was 5.5% (95% CI: 3.4, 8.6), 16.3% (95% CI: 12.9, 21.1), and 31.0% (95% CI: 25.4, 36.5) in each of the first 3 follow-up years, respectively. The factors associated with a greater risk of conversion from MCI to AD included smoking status, ApoE4 carrier status, right hippocampal volume (rt. HV), left temporal lobe volume, and scores on the Revised Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-C). The risk classification of the ADAS-Cog-C or Preclinical Alzheimer Cognitive Composite (PACC) score combined with the rt. HV showed a conversion difference among the groups at every annual follow-up. A simple risk classification using the rt. HV and neuropsychological test scores, including those from the ADAS-Cog-C and PACC, could be a practicable and efficient approach to indentify individuals at risk of all-cause dementia.

Longitudinal brain atrophy rates in presymptomatic genetic frontotemporal dementia

AbstractBackgroundIn light of upcoming clinical trials for genetic frontotemporal dementia (FTD), it is important to identify at what age brain atrophy rates start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We aimed to investigate longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD, using normative brain volumetry software.Method34 GRN, eight MAPT, and 14 C9orf72 presymptomatic mutation carriers underwent longitudinal volumetric T1‐weighted MRI of the brain with a one‐ to two‐year interval (mean number of scans = 3.5, SD = 1.6). Images were automatically analyzed with Quantib® ND which consisted of volume measurements (CSF and grey + white matter) of lobes (left, right, and combined), cerebellum, and hippocampus. All volumes were compared to reference centile curves based on a large population‐derived sample of non‐demented individuals (n = 4951). Mixed‐effects models were fitted to analyze atrophy rates of the different gene groups as a function of age, and were corrected for sex, head coil, and scanner software version.ResultAtrophy rates of the total brain, frontal lobe, and temporal lobe differed between gene groups (all p&lt;0.002). GRN mutation carriers declined faster than the reference centile curves for all brain areas, though relative volumes remained between 5th and 75th percentile between the ages of 45 – 70. In MAPT mutation carriers, frontal lobe volume was already at the 5th percentile at age 45, and showed further decline between the ages 50‐60. Temporal lobe volume started in the 50th percentile at age 45, but showed fastest decline over time compared to other brain structures. Frontal, temporal, parietal and cerebellar volume already started below the 5th percentile compared to the reference centile curves at age 45 for C9orf72 mutation carriers, but there was minimal decline over time until the age of 60.ConclusionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease‐tracking and staging biomarkers in genetic FTD.

Age-related and amyloid-beta-independent tau deposition and its downstream effects.

Amyloid-β (Aβ) is hypothesized to facilitate the spread of tau pathology beyond the medial temporal lobe. However, there is evidence that, independently of Aβ, age-related tau pathology might be present outside of the medial temporal lobe. We therefore aimed to study age-related Aβ-independent tau deposition outside the medial temporal lobe in two large cohorts and to investigate potential downstream effects of this on cognition and structural measures. We included 545 cognitively unimpaired adults (40-92 years) from the BioFINDER-2 study (in vivo) and 639 (64-108 years) from the Rush Alzheimer's Disease Center cohorts (ex vivo). 18F-RO948- and 18F-flutemetamol-PET standardized uptake value ratios were calculated for regional tau and global/regional Aβ in vivo. Immunohistochemistry was used to estimate Aβ load and tangle density ex vivo. In vivo medial temporal lobe volumes (subiculum, cornu ammonis 1) and cortical thickness (entorhinal cortex, Brodmann area 35) were obtained using Automated Segmentation for Hippocampal Subfields packages. Thickness of early and late neocortical Alzheimer's disease regions was determined using FreeSurfer. Global cognition and episodic memory were estimated to quantify cognitive functioning. In vivo age-related tau deposition was observed in the medial temporal lobe and in frontal and parietal cortical regions, which was statistically significant when adjusting for Aβ. This was also observed in individuals with low Aβ load. Tau deposition was negatively associated with cortical volumes and thickness in temporal and parietal regions independently of Aβ. The associations between age and cortical volume or thickness were partially mediated via tau in regions with early Alzheimer's disease pathology, i.e. early tau and/or Aβ pathology (subiculum/Brodmann area 35/precuneus/posterior cingulate). Finally, the associations between age and cognition were partially mediated via tau in Brodmann area 35, even when including Aβ-PET as covariate. Results were validated in the ex vivo cohort showing age-related and Aβ-independent increases in tau aggregates in and outside the medial temporal lobe. Ex vivo age-cognition associations were mediated by medial and inferior temporal tau tangle density, while correcting for Aβ density. Taken together, our study provides support for primary age-related tauopathy even outside the medial temporal lobe in vivo and ex vivo, with downstream effects on structure and cognition. These results have implications for our understanding of the spreading of tau outside the medial temporal lobe, also in the context of Alzheimer's disease. Moreover, this study suggests the potential utility of tau-targeting treatments in primary age-related tauopathy, likely already in preclinical stages in individuals with low Aβ pathology.

Olfactory function reflects episodic memory performance and atrophy in the medial temporal lobe in individuals at risk for Alzheimer’s disease

We examined cognitive domains and brain regions associated with olfactory performance in cognitively unimpaired older adults (CU-OAs) and individuals with or at risk for Alzheimer’s Disease (AD). We compared CU-OAs (N = 55), individuals with subjective cognitive decline (SCD, N = 55), mild cognitive impairment (MCI, N = 101), and AD (N = 45) on measures of olfactory function (Brief Smell Identification Test), cognition (episodic and semantic memory), and medial temporal lobe thickness and volume. Analyses controlled for age, sex, education, and total intracranial volume. Olfactory function decreased from SCD to MCI to AD. CU-OAs outperformed all groups except SCDs on tests of cognition and olfaction. Although these measures did not differ between the CU-OAs and SCDs, olfactory function correlated with episodic memory tests and with entorhinal cortex atrophy only in the SCD group. Olfactory function also correlated with hippocampal volume and right-hemisphere entorhinal cortex thickness in the MCI group. Olfactory dysfunction reflects medial temporal lobe integrity and memory performance in a group at risk for AD with normal cognition and olfaction.

Sex-specific effects of SNAP-25 genotype on verbal memory and Alzheimer's disease biomarkers in clinically normal older adults.

We tested sex-dependent associations of variation in the SNAP-25 gene, which encodes a presynaptic protein involved in hippocampal plasticity and memory, on cognitive and Alzheimer's disease (AD) neuroimaging outcomes in clinically normal adults. Participants were genotyped for SNAP-25 rs1051312 (T>C; SNAP-25 expression: C-allele>T/T). In a discovery cohort (N=311), we tested the sex by SNAP-25 variant interaction on cognition, Aβ-PET positivity, and temporal lobe volumes. Cognitive models were replicated in an independent cohort (N=82). In the discovery cohort, C-allele carriers exhibited better verbal memory and language, lower Aβ-PET positivity rates, and larger temporal volumes than T/T homozygotes among females, but not males. Larger temporal volumes related to better verbal memory only in C-carrier females. The female-specific C-allele verbal memory advantage was evidenced in the replication cohort. In females, genetic variation in SNAP-25 is associated with resistance to amyloid plaque formation and may support verbal memory through fortification of temporal lobe architecture. The SNAP-25 rs1051312 (T>C) C-allele results in higher basal SNAP-25 expression. C-allele carriers had better verbal memory in clinically normal women, but not men. Female C-carriers had higher temporal lobe volumes, which predicted verbal memory. Female C-carriers also exhibited the lowest rates of amyloid-beta PET positivity. The SNAP-25 gene may influence female-specific resistance to Alzheimer's disease (AD).

Computer assisted diagnosis of Alzheimer's disease using statistical likelihood-ratio test.

The purpose of this work is to present a computer assisted diagnostic tool for radiologists in their diagnosis of Alzheimer's disease. A statistical likelihood-ratio procedure from signal detection theory was implemented in the detection of Alzheimer's disease. The probability density functions of the likelihood ratio were constructed by using medial temporal lobe (MTL) volumes of patients with Alzheimer's disease (AD) and normal controls (NC). The volumes of MTL as well as other anatomical regions of the brains were calculated by the FreeSurfer software using T1 weighted MRI images. The MRI images of AD and NC were downloaded from the database of Alzheimer's disease neuroimaging initiative (ADNI). A separate dataset of minimal interval resonance imaging in Alzheimer's disease (MIRIAD) was used for diagnostic testing. A sensitivity of 89.1% and specificity of 87.0% were achieved for the MIRIAD dataset which are better than the 85% sensitivity and specificity achieved by the best radiologists without input of other patient information.

Updated imaging and phylogenetic comparative methods reassess relative temporal lobe size in anthropoids and modern humans.

Two decades ago, Rilling and Seligman, hereafter abbreviated to RAS Study, suggested modern humans had relatively larger temporal lobes for brain size compared to other anthropoids. Despite many subsequent studies drawing conclusions about the evolutionary implications for the emergence of unique cerebral specializations in Homo sapiens, no re-assessment has occurred using updated methodologies. We reassessed the association between right temporal lobe volume (TLV) and right hemisphere volume (HV) in the anthropoid brain. In a sample compiled de novo by us, T1-weighted in vivo Magnetic Resonance Imaging (MRI) scans of 11 extant anthropoid species were calculated by-voxel from the MRI and the raw data from RAS Study directly compared to our sample. Phylogenetic Generalized Least-Squares (PGLS) regression and trait-mapping using Blomberg's K (kappa) tested the correlation between HV and TLV accounting for anthropoid phylogeny, while bootstrapped PGLS regressions tested difference in slopes and intercepts between monkey and ape subsamples. PGLS regressions indicated statistically significant correlations (r2 < 0.99; p ≤ 0.0001) between TLV and HV with moderate influence from phylogeny (K ≤ 0.42). Bootstrapped PGLS regression did not show statistically significant differences in slopes between monkeys and apes but did for intercepts. In our sample, human TLV was not larger than expected for anthropoids. Updated imaging, increased sample size and advanced statistical analyses did not find statistically significant results that modern humans possessed a disproportionately large temporal lobe volume compared to the general anthropoid trend. This has important implications for human and non-human primate brain evolution.

Transdiagnostic overlap in brain correlates of affective and cognitive theory of mind deficits.

Social cognitive symptoms characterize multiple neurological disorders, including brain tumours and neurodegeneration. Recently, Campanella and colleagues1 investigated deficits in cognitive and affective theory of mind (TOM) in 105 tumour patients using a non-verbal task of 18 stimuli that required patients to select one out of three possible endings of a cartoon story, i.e. the Story-based Empathy Task (SET).2 The SET includes three conditions [Causal Inference (CI), Intention Attribution (IA) and Emotion Attribution (EA)], reflecting the type of inference the items tap into: inference of physical properties, intentions, or characters’ emotional state, respectively. The behavioural results of Campanella’s study revealed specific EA deficits in patients with temporal lobe tumours. Furthermore, the authors used parcel-based lesion-symptom mapping (PLSM) and reported an association between a right anterior temporal cluster and EA performance. Right amygdalar lesions showed a stronger association with EA than with IA. The association between EA deficits and amygdalar volume has also been also reported in behavioural variant frontotemporal dementia (bvFTD),3 a neurodegenerative disorder, characterized by deficits in social cognition, including cognitive and affective TOM. Consistent with the findings of Campanella, we also observed an association between performance on the EA condition and grey matter volume of the right temporal lobe and amygdala3 (Fig. 1). As documented by Campanella and colleagues, such common neural correlates of EA performance largely overlap with a ‘reasoning about emotions’ network derived from a recent meta-analysis of functional brain imaging studies in healthy participants.4 These combined findings converge in supporting a critical role of the right amygdala and temporal lobe in emotion attribution.

Differential association of endothelial function with brain structure in youth with versus without bipolar disorder

BackgroundMood symptoms and disorders are associated with impaired endothelial function, a marker of early atherosclerosis. Given the increased vascular burden and neurostructural differences among individuals with mood disorders, we investigated the endothelial function and brain structure interface in relation to youth bipolar disorder (BD). MethodsThis cross-sectional case-controlled study included 115 youth, ages 13–20 years (n = 66 BD; n = 49 controls [CG]). Cortical thickness and volume for regions of interest (ROI; insular cortex, ventrolateral prefrontal cortex [vlPFC], temporal lobe) were acquired from FreeSurfer processed T1-weighted MRI images. Endothelial function was assessed using pulse amplitude tonometry, yielding a reactive hyperemia index (RHI). ROI and vertex-wise analyses controlling for age, sex, obesity, and intracranial volume investigated for RHI-neurostructural associations, and RHI-by-diagnosis interactions. ResultsIn ROI analyses, higher RHI (i.e., better endothelial function) was associated with lower thickness in the insular cortex (β = −0.19, pFDR = 0.03), vlPFC (β = −0.30, pFDR = 0.003), and temporal lobe (β = −0.22, pFDR = 0.01); and lower temporal lobe volume (β = −0.16, pFDR = 0.01) in the overall sample. In vertex-wise analyses, higher RHI was associated with lower cortical thickness and volume in the insular cortex, prefrontal cortex (e.g., vlPFC), and temporal lobe. Additionally, higher RHI was associated with lower vlPFC and temporal lobe volume to a greater extent in youth with BD vs. CG. ConclusionsBetter endothelial function was associated with lower regional brain thickness and volume, contrasting the hypothesized associations. Additionally, we found evidence that this pattern was exaggerated in youth with BD. Future studies examining the direction of the observed associations and underlying mechanisms are warranted.

Handgrip Strength Is Related to Hippocampal and Lobar Brain Volumes in a Cohort of Cognitively Impaired Older Adults with Confirmed Amyloid Burden.

Strength and mobility are essential for activities of daily living. With aging, weaker handgrip strength, mobility, and asymmetry predict poorer cognition. We therefore sought to quantify the relationship between handgrip metrics and volumes quantified on brain magnetic resonance imaging (MRI). To model the relationships between handgrip strength, mobility, and MRI volumetry. We selected 38 participants with Alzheimer's disease dementia: biomarker evidence of amyloidosis and impaired cognition. Handgrip strength on dominant and non-dominant hands was measured with a hand dynamometer. Handgrip asymmetry was calculated. Two-minute walk test (2MWT) mobility evaluation was combined with handgrip strength to identify non-frail versus frail persons. Brain MRI volumes were quantified with Neuroreader. Multiple regression adjusting for age, sex, education, handedness, body mass index, and head size modeled handgrip strength, asymmetry and 2MWT with brain volumes. We modeled non-frail versus frail status relationships with brain structures by analysis of covariance. Higher non-dominant handgrip strength was associated with larger volumes in the hippocampus (p = 0.02). Dominant handgrip strength was related to higher frontal lobe volumes (p = 0.02). Higher 2MWT scores were associated with larger hippocampal (p = 0.04), frontal (p = 0.01), temporal (p = 0.03), parietal (p = 0.009), and occipital lobe (p = 0.005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes. Greater handgrip strength and mobility were related to larger hippocampal and lobar brain volumes. Interventions focused on improving handgrip strength and mobility may seek to include quantified brain volumes on MR imaging as endpoints.

Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer's Disease.

The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina. To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. 75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes. RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.