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IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Abstract Background The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking. Methods BioFINDER-2 participants with memory impairment, abnormal amyloid-β and tau-PET were included. Forty-one amnestic EOAD individuals ≤65 years and, as comparison, late-onset AD (aLOAD, ≥70 years, n = 154) and amyloid-β-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. Results AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups: aLOAD showed thinner entorhinal cortices than aEOAD; aEOAD showed thinner parietal regions than aLOAD. aEOAD showed lower white matter hyperintensities than aLOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity were found. Conclusions We found evidence for MTL atrophy in amnestic EOAD and overall similar levels to aLOAD of MTL tau pathology and co-pathologies.

Abstract Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer’s Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research.

A description of a laboratory confirmed clinical case of generalized Varicella Zoster infection in a patient with lymphogranulomatosis after bone marrow transplantation is presented.Detection of the Varicella Zoster virus in biological material was carried out by real-time PCR using the RealBest DNA VZV test system manufactured by Vector-BEST, Russian Federation. Isolation of viral DNA from biological material was performed using the ArtRNA MiniSpin kit (ArtBioTech, Belarus) or QIAamp DNA mini kit (QIAGEN, Germany).The disease had an atypically severe course with a multiorgan lesion, represented not only by lesions of the skin and mucous membranes, but also by the development of encephalitis, myocarditis, and pneumonia. The disease was characterized by an acute onset, with a pronounced intoxication syndrome, signs of pancreatitis with the appearance of a widespread vesicular rash on the trunk and extremities, prone to fusion, located, including on the scalp, on the feet and palms. The disease was complicated by a secondary bacterial infection, in connection with which the patient received both antiviral treatment and broad-spectrum antibiotic therapy.The virus was assigned to clade 3 (or E2 genotype according to the old classification), the same genotype as the viruses circulating in Minsk. This case is the first described case of generalized VZV infection in the Republic of Belarus, confirmed by laboratory using molecular genetic methods.

Abstract Structures of macromolecules in their native state provide unique unambiguous insights into their functions. Cryo-electron tomography combined with subtomogram averaging demonstrated the power to solve such structures in situ at resolutions in the range of 3 Angstrom for some macromolecules. In order to be applicable to the structural determination of the majority of macromolecules observable in cells in limited amounts, processing of tomographic data has to be performed in a high-throughput manner. Here we present TomoBEAR—a modular configurable workflow engine for streamlined processing of cryo-electron tomographic data for subtomogram averaging. TomoBEAR combines commonly used cryo-EM packages with reasonable presets to provide a transparent (“white box”) approach for data management and processing. We demonstrate applications of TomoBEAR to two data sets of purified macromolecular targets, to an ion channel RyR1 in a membrane, and the tomograms of plasma FIB-milled lamellae and demonstrate the ability to produce high-resolution structures. TomoBEAR speeds up data processing, minimizes human interventions, and will help accelerate the adoption of in situ structural biology by cryo-ET. The source code and the documentation are freely available.

Alzheimer's disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in 18F-flortaucipir vs. 18F-fluorodeoxyglucose positron emission tomography as markers of T and neuronal hypometabolism (NM) in 289 symptomatic patients from the Alzheimer's Disease Neuroimaging Initiative. We identified six T/NM clusters with differing limbic and cortical patterns. The canonical group was defined as the T/NM pattern with lowest regression residuals. Groups resilient to T had less hypometabolism than expected relative to T and displayed better cognition than the canonical group. Groups susceptible to T had more hypometabolism than expected given T and exhibited worse cognitive decline, with imaging and clinical measures concordant with non-AD copathologies. Together, T/NM mismatch reveals distinct imaging signatures with pathobiological and prognostic implications for AD.

ObjectiveTau neurofibrillary tangles (T) are the primary driver of downstream neurodegeneration (N) and subsequent cognitive impairment in Alzheimer's disease (AD). However, there is substantial variability in the T-N relationship - manifested in higher or lower atrophy than expected for level of tau in a given brain region. The goal of this study was to determine if region-based quantitation of this variability allows for identification of underlying modulatory factors, including polypathology.MethodsCortical thickness (N) and 18 F-Flortaucipir SUVR (T) were computed in 104 gray matter regions from a cohort of cognitively-impaired, amyloid-positive (A+) individuals. Region-specific residuals from a robust linear fit between SUVR and cortical thickness were computed as a surrogate for T-N mismatch. A summary T-N mismatch metric defined using residuals were correlated with demographic and imaging-based modulatory factors, and to partition the cohort into data-driven subgroups.ResultsThe summary T-N mismatch metric correlated with underlying factors such as age and burden of white matter hyperintensity lesions. Data-driven subgroups based on clustering of residuals appear to represent different biologically relevant phenotypes, with groups showing distinct spatial patterns of higher or lower atrophy than expected.InterpretationThese data support the notion that a measure of deviation from a normative relationship between tau burden and neurodegeneration across brain regions in individuals on the AD continuum captures variability due to multiple underlying factors, and can reveal phenotypes, which if validated, may help identify possible contributors to neurodegeneration in addition to tau, which may ultimately be useful for cohort selection in clinical trials. ANN NEUROL 2021;90:751-762.

Abstract Background Crucial to the success of clinical trials targeting early Alzheimer’s disease (AD) is recruiting participants who are more likely to progress over the course of the trials. We hypothesize that a combination of plasma and structural MRI biomarkers, which are less costly and non-invasive, is predictive of longitudinal progression measured by atrophy and cognitive decline in early AD, providing a practical alternative to PET or cerebrospinal fluid biomarkers. Methods Longitudinal T1-weighted MRI, cognitive (memory-related test scores and clinical dementia rating scale), and plasma measurements of 245 cognitively normal (CN) and 361 mild cognitive impairment (MCI) patients from ADNI were included. Subjects were further divided into β-amyloid positive/negative (Aβ+/Aβ−)] subgroups. Baseline plasma (p-tau181 and neurofilament light chain) and MRI-based structural medial temporal lobe subregional measurements and their association with longitudinal measures of atrophy and cognitive decline were tested using stepwise linear mixed effect modeling in CN and MCI, as well as separately in the Aβ+/Aβ− subgroups. Receiver operating characteristic (ROC) analyses were performed to investigate the discriminative power of each model in separating fast and slow progressors (first and last terciles) of each longitudinal measurement. Results A total of 245 CN (35.0% Aβ+) and 361 MCI (53.2% Aβ+) participants were included. In the CN and MCI groups, both baseline plasma and structural MRI biomarkers were included in most models. These relationships were maintained when limited to the Aβ+ and Aβ− subgroups, including Aβ− CN (normal aging). ROC analyses demonstrated reliable discriminative power in identifying fast from slow progressors in MCI [area under the curve (AUC): 0.78–0.93] and more modestly in CN (0.65–0.73). Conclusions The present data support the notion that plasma and MRI biomarkers, which are relatively easy to obtain, provide a prediction for the rate of future cognitive and neurodegenerative progression that may be particularly useful in clinical trial stratification and prognosis. Additionally, the effect in Aβ− CN indicates the potential use of these biomarkers in predicting a normal age-related decline.

Spurred by availability of automatic segmentation software, in vivo MRI investigations of human hippocampal subfield volumes have proliferated in the recent years. However, a majority of these studies apply automatic segmentation to MRI scans with approximately 1 × 1 × 1 mm3 resolution, a resolution at which the internal structure of the hippocampus can rarely be visualized. Many of these studies have reported contradictory and often neurobiologically surprising results pertaining to the involvement of hippocampal subfields in normal brain function, aging, and disease. In this commentary, we first outline our concerns regarding the utility and validity of subfield segmentation on 1 × 1 × 1 mm3 MRI for volumetric studies, regardless of how images are segmented (i.e., manually or automatically). This image resolution is generally insufficient for visualizing the internal structure of the hippocampus, particularly the stratum radiatum lacunosum moleculare, which is crucial for valid and reliable subfield segmentation. Second, we discuss the fact that automatic methods that are employed most frequently to obtain hippocampal subfield volumes from 1 × 1 × 1 mm3 MRI have not been validated against manual segmentation on such images. For these reasons, we caution against using volumetric measurements of hippocampal subfields obtained from 1 × 1 × 1 mm3 images.

AimsLewy body diseases (LBD) are characterized by alpha-synuclein (SYN) pathology, but comorbid Alzheimer's disease (AD) pathology is common and the relationship between these pathologies in microanatomic hippocampal subfields is understudied. Here we use digital histological methods to test the association between hippocampal SYN pathology and the distribution of tau and amyloid-beta (Aβ) pathology in LBD and contrast with AD subjects. We also correlate pathologic burden with antemortem episodic memory testing.MethodsHippocampal sections from 49 autopsy-confirmed LBD cases, 30 with no/low AD copathology (LBD - AD) and 19 with moderate/severe AD copathology (LBD + AD), and 30 AD patients were stained for SYN, tau, and Aβ. Sections underwent digital histological analysis of subfield pathological burden which was correlated with antemortem memory testing.ResultsLBD - AD and LBD + AD had similar severity and distribution of SYN pathology (P > 0.05), CA2/3 being the most affected subfield (P

Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively. The neural substrates of these complex social disorders remain unclear. Here, we present a comparative imaging and postmortem study of two patients, one with FTLD-TDP (subtype C) and one with FTLD-tau (subtype Pick disease), who both developed new rigid belief systems. The FTLD-TDP patient developed a complex set of values centered on positivity and associated with specific physical and behavioral features of pigs, while the FTLD-tau patient developed compulsive, goal-directed behaviors related to general themes of positivity and spirituality. Neuroimaging showed left-predominant temporal atrophy in the FTLD-TDP patient and right-predominant frontotemporal atrophy in the FTLD-tau patient. Consistent with antemortem cortical atrophy, histopathologic examinations revealed severe loss of neurons and myelin predominantly in the anterior temporal lobes of both patients, but the FTLD-tau patient showed more bilateral, dorsolateral involvement featuring greater pathology and loss of projection neurons and deep white matter. These findings highlight that the regions within and connected to anterior temporal lobes may have differential vulnerability to distinct FTLD proteinopathies and serve important roles in human belief systems.

IntroductionHeterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.MethodsOur international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption.ResultsThis progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures.DiscussionA harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Crop infection is a stress factor for plants. The development and spread of fungal phytopathogens (Fusarium, Bipolaris, Alternaria, etc.) of the root system leads to a significant decrease in both quantitative, and qualitative parameters of grain crop productivity. The current paper has presented the data (2011–2018) on the study of subsoil parts of spring wheat plants when they are damaged by root rots of various etiologies, depending on the forecrops, agricultural technology and plant protection products. In the conditions of the Omsk region, the introduction of rapeseed into field crop rotations is justified. The grain crop has a positive effect on improving the phytosanitary condition of the soil and crops. There has been established that the greatest spread of infection on the root system of plants is identified on wheat sown in fallow (35–46 %), the minimum spread after rapeseed (7–16 %). Seeds of bluegrass weeds during protective tillage are concentrated in an uppermost (0–10 cm) soil layer. The increased weed infestation of agrophytocenosis reduces the competitiveness of cultivated plants and, as a result, the population of B. sorokiniana conidia in soil increases, creating unfavorable conditions for spring wheat development, especially during the initial period of growth. The highest crop productivity, regardless of a forecrop, mean for intensification options, was provided by moldboard tillage with 3.02 t/ha (wheat sown in fallow); 2.60 t/ha (wheat sown after wheat) and 2.15 t/ha (wheat sown\ after rapeseed). With a protective tillage, there was grain productivity decrease on 0.20 t/ha (wheat sown in fallow); 0.22 t/ha (wheat sown after wheat) and 0.12 t/ha (wheat sown after rapeseed) t/ha, respectively, in comparison with a moldboard technology. When fertilizing and herbicidal-fungicidal treatment of sowings during a vegetation period of plants, there is a slight difference between agricultural technologies. The complex use of chemicals reduces the infection of agrophytocenosis on 7–11 % and increases spring wheat productivity upto 4.14 t/ha (on 98 %) relative to extensive agricultural technology.

Social stress is common among people and is considered one of the causes of the declining birth rate. Predisposition to stress and stress-induced disorders is largely determined genetically. We hypothesized that due to differences in stress resistance, carriers of different genetic variants of genes associated with stress resilience and stress-induced diseases may have dissimilar numbers of offspring under conditions of long-term social stress. To test this hypothesis, a comparative analysis of frequencies of seven common polymorphic regions [exon 3 variable number of tandem repeats (VNTR) of the DRD4 gene, rs4680 of COMT, STin2 VNTR and the 5-HTTLPR (rs774676466) insertion/deletion polymorphism of SLC6A4, rs4570625 of TPH2, rs6265 of BDNF, and rs258747 of NR3C1] was performed on standardized groups of randomly selected adolescents born before, during, and after severe socioeconomic deprivation (the crisis of the 1990s in Russia). There were significant differences in frequencies of “long” alleles of the DRD4 gene (p = 0.020, χ2 = 5.492) and rs4680 (p = 0.022, χ2 = 5.289) in the “crisis” group as compared to the combined “noncrisis” population. It is possible that the dopaminergic system had an impact on the successful adaptation of a person to social stress.

Today, cluster analysis is one of the most effective tools for processing large amounts of information and is used wherever computing technology is used, since data and the results of their analysis play an increasingly important role in modern information society, and clustering allows for a better understanding of this data. Whenever it is necessary to classify a large amount of information of this kind and present it in a form suitable for further processing, cluster analysis turns out to be very useful and effective. The analysis of 48-year observations on 107 variables (crop yield, crop rotation by tillage techniques and means of intensification, crop contamination, soil moisture content under sowing during the growing season, the sum of non-vegetative precipitation, the sum of decadal precipitation and average decadal air temperatures during the growing season) using clustering by the Ward method allowed us to group observations into 6 clusters and use them to analyze the studied variables. An average positive relationship of soil moisture content before sowing with the amount of non-vegetative precipitation and a negative one with air temperature in May has been established. Linear regression equations of the positive relationship of yield with the consumption of soil moisture during the growing season, precipitation in June-July and negative clogging and average air temperature in May-July were selected.

In the arid agricultural landscapes of Western Siberia, the productivity of leading grain crops is determined by adaptive agrotechnology, the use of intensification tools and hydrothermal conditions. The relatively low (up to 1.40-1.70 t/ha) and unstable yield of grain crops is mainly due to the limited use of fertilizers (up to 20 kg/ha), the aridity of the climate. Long-term studies have established that in the southern forest-steppe agricultural landscapes, precipitation of all periods of the year, except for spring, has an impact on grain productivity. Autumn moisture reserves determine the yield of spring wheat after its corn predecessor by 51% in general, up to 21% for steam, and only 13% for barley. The conjugacy of spring soil moisture is higher on wheat, on flat-cutting processing than on plowing, on intensive agrotechnology. The most significant combination of spring moisture reserves and summer precipitation (June-1st decade of July). The dependence of wheat yield after steam reaches a high conjugacy (r=0.77-0.84), after corn – from medium to strong (up to 59-71%). The correlation of yield with the temperature regime during the growing season is negative. The conjugacy with the value of GTK is more pronounced after the corn precursor – 46%, steam – up to 30%, barley only 8%, the greatest dependence was revealed with the Coefficient of dryness. The predicted yield level of high–quality grain with complex chemicalization and soil protection treatment with average long-term hydrothermal parameters on wheat after the corn precursor reaches 2.8 t/ha with a probability of up to 76%, and 3.4 t/ha for steam. To optimize the water regime, it is necessary to use additional moisture-accumulating agricultural techniques.

We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

BackgroundMajor depressive disorder (MDD) is a prevalent health problem with complex pathophysiology that is not clearly understood. Prior work has implicated the hippocampus in MDD, but how hippocampal subfields influence or are affected by MDD requires further characterization with high-resolution data. This will help ascertain the accuracy and reproducibility of previous subfield findings in depression as well as correlate subfield volumes with MDD symptom scores. The objective of this study was to assess volumetric differences in hippocampal subfields between MDD patients globally and healthy controls (HC) as well as between a subset of treatment-resistant depression (TRD) patients and HC using automatic segmentation of hippocampal subfields (ASHS) software and ultra-high field MRI.MethodsThirty-five MDD patients and 28 HC underwent imaging using 7-Tesla MRI. ASHS software was applied to the imaging data to perform automated hippocampal segmentation and provide volumetrics for analysis. An exploratory analysis was also performed on associations between symptom scores for diagnostic testing and hippocampal subfield volumes.ResultsCompared to HC, MDD and TRD patients showed reduced right-hemisphere CA2/3 subfield volume (p = 0.01, η2 = 0.31 and p = 0.3, η2 = 0.44, respectively). Additionally, negative associations were found between subfield volumes and life-stressor checklist scores, including left CA1 (p = 0.041, f2 = 0.419), left CA4/DG (p = 0.010, f2 = 0.584), right subiculum total (p = 0.038, f2 = 0.354), left hippocampus total (p = 0.015, f2 = 0.134), and right hippocampus total (p = 0.034, f2 = 0.110). Caution should be exercised in interpreting these results due to the small sample size and low power.ConclusionDetermining biomarkers for MDD and TRD pathophysiology through segmentation on high-resolution MRI data and understanding the effects of stress on these regions can enable better assessment of biological response to treatment selection and may elucidate the underlying mechanisms of depression.

ObjectiveSubfield-specific measurements provide superior information in the early stages of neurodegenerative diseases compared to global hippocampal measurements. The overall goal was to systematically compare the performance of five representative manual and automated T1 and T2 based subfield labeling techniques in a sub-set of the ADNI2 population.MethodsThe high resolution T2 weighted hippocampal images (T2-HighRes) and the corresponding T1 images from 106 ADNI2 subjects (41 controls, 57 MCI, 8 AD) were processed as follows. A. T1-based: 1. Freesurfer + Large-Diffeomorphic-Metric-Mapping in combination with shape analysis. 2. FreeSurfer 5.1 subfields using in-vivo atlas. B. T2-HighRes: 1. Model-based subfield segmentation using ex-vivo atlas (FreeSurfer 6.0). 2. T2-based automated multi-atlas segmentation combined with similarity-weighted voting (ASHS). 3. Manual subfield parcellation. Multiple regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach.ResultsSubfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between controls and MCI (ES: 0.27 vs 0.11). T2-HighRes approaches outperformed T1 approaches for the detection of early stage atrophy (ES: 0.27 vs.0.10), amyloid positivity (ES: 0.11 vs 0.04), and cognitive associations (ES: 0.22 vs 0.19).ConclusionsT2-HighRes subfield approaches outperformed whole hippocampus and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry.