Multimodal Discrimination of Alzheimer’s Disease Based on Regional Cortical Atrophy and Hypometabolism

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

Download Full-text

The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer's disease) with FDG-PET

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.74.11.1521 ◽

2003 ◽

Vol 74 (11) ◽

pp. 1521-1529 ◽

Cited By ~ 126

Author(s):

P J Nestor

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Fdg Pet ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy

Download Full-text

Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607

Acta Neuropathologica ◽

10.1007/s00401-021-02294-3 ◽

2021 ◽

Vol 141 (5) ◽

pp. 697-708

Author(s):

Yang Shi ◽

Alexey G. Murzin ◽

Benjamin Falcon ◽

Alexander Epstein ◽

Jonathan Machin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Small Molecules ◽

Binding Sites ◽

Binding Activity ◽

Cortical Atrophy ◽

Binding Modes ◽

Major Site ◽

Age Related ◽

Positron Emission

AbstractTau and Aβ assemblies of Alzheimer’s disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the β-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.

Download Full-text

Diﬃculties in diagnosing atypical variants of Alzheimer’s disease

Russian neurological Journal ◽

10.30629/2658-7947-2021-26-5-16-23 ◽

2021 ◽

Vol 26 (5) ◽

pp. 16-23

Author(s):

A. A. Tappakhov ◽

T. Ya. Nikolaeva ◽

T. E. Popova ◽

N. A. Shnayder

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Picture ◽

Short Term Memory ◽

Late Onset ◽

Early Stage ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy ◽

Short Term

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

Download Full-text

Clinical Characteristic in Primary Progressive Aphasia in Relation to Alzheimer’s Disease Biomarkers

Journal of Alzheimer s Disease ◽

10.3233/jad-210392 ◽

2021 ◽

pp. 1-13

Author(s):

Sung Hoon Kang ◽

Hanna Cho ◽

Jiho Shin ◽

Hang-Rai Kim ◽

Young Noh ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Language Impairment ◽

Amyloid Β ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Clinical Feature ◽

Progressive Aphasia ◽

Disease Biomarkers ◽

Primary Progressive

Background: Primary progressive aphasia (PPA) is associated with amyloid-β (Aβ) pathology. However, clinical feature of PPA based on Aβ positivity remains unclear. Objective: We aimed to assess the prevalence of Aβ positivity in patients with PPA and compare the clinical characteristics of patients with Aβ-positive (A+) and Aβ-negative (A–) PPA. Further, we applied Aβ and tau classification system (AT system) in patients with PPA for whom additional information of in vivo tau biomarker was available. Methods: We recruited 110 patients with PPA (41 semantic [svPPA], 27 non-fluent [nfvPPA], 32 logopenic [lvPPA], and 10 unclassified [ucPPA]) who underwent Aβ-PET imaging at multi centers. The extent of language impairment and cortical atrophy were compared between the A+ and A–PPA subgroups using general linear models. Results: The prevalence of Aβ positivity was highest in patients with lvPPA (81.3%), followed by ucPPA (60.0%), nfvPPA (18.5%), and svPPA (9.8%). The A+ PPA subgroup manifested cortical atrophy mainly in the left superior temporal/inferior parietal regions and had lower repetition scores compared to the A–PPA subgroup. Further, we observed that more than 90%(13/14) of the patients with A+ PPA had tau deposition. Conclusion: Our findings will help clinicians understand the patterns of language impairment and cortical atrophy in patients with PPA based on Aβ deposition. Considering that most of the A+ PPA patents are tau positive, understanding the influence of Alzheimer’s disease biomarkers on PPA might provide an opportunity for these patients to participate in clinical trials aimed for treating atypical Alzheimer’s disease.

Download Full-text

O4-03-06: Effects of cortical visual impairment on navigational ability in posterior cortical atrophy and typical Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.07.485 ◽

2015 ◽

Vol 11 (7S_Part_6) ◽

pp. P274-P274 ◽

Cited By ~ 1

Author(s):

Keir X.X. Yong ◽

Catherine Holloway ◽

Amelia Carton ◽

Biao Yang ◽

Tatsuto Suzuki ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Visual Impairment ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy ◽

Cortical Visual Impairment

Download Full-text

Posterior cortical atrophy: A rare variant of Alzheimer’s disease

Neurology International ◽

10.4081/ni.2018.7665 ◽

2018 ◽

Vol 10 (2) ◽

Cited By ~ 1

Author(s):

Michael A. Meyer ◽

Stephen A. Hudock

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Visual Cortex ◽

Primary Visual Cortex ◽

Photon Emission ◽

Occipital Cortex ◽

Cortical Atrophy ◽

Emission Computed Tomography ◽

Posterior Cortical Atrophy ◽

Homonymous Hemianopsia

Posterior cortical atrophy is a rare condition first described in 1988 involving progressive degeneration and atrophy of the occipital cortex, often recognized after an unexplained homonymous hemianopsia may be discovered. We report a case in association with Alzheimer’s disease in a 77-year-old female, who underwent brain single-photon emission computed tomography as well brain positron emission tomography using Florbetapir to further evaluate progressive cognitive decline. The patient had also been followed in Ophthalmology for glaucoma, where a progressive unexplained change in her visual field maps were noted over one year consistent with a progressive right homonymous hemianopsia. This rare combination of findings in association with her dementia led to a detailed review of all her imaging studies, concluding with the surprising recognition for a clear hemi-atrophy of the primary left occipital cortex was occurring, consistent with Alzheimer’s disease affecting the primary visual cortex. Further awareness of this disease pattern is needed, as Alzheimer’s disease typically does not affect the primary visual cortex; other conditions to consider in general include Lewy Body dementia, cortico-basal degeneration and prion disease.

Download Full-text

P1-352: Cortical atrophy rates in Alzheimer's disease and mild cognitive impairment from the ADNI study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.632 ◽

2011 ◽

Vol 7 ◽

pp. S225-S225 ◽

Cited By ~ 1

Author(s):

Christian Spenger ◽

Simon Eskildsen ◽

Niclas Sjogren ◽

Per Julin ◽

Eric Westman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cortical Atrophy

Download Full-text

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer’s Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position

Journal of Alzheimer s Disease ◽

10.3233/jad-210378 ◽

2021 ◽

pp. 1-17

Author(s):

Ingrid Daae Rasmussen ◽

Nya Mehnwolo Boayue ◽

Matthias Mittner ◽

Martin Bystad ◽

Ole K. Grnli ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Electric Field ◽

Computational Modeling ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Cortical Atrophy ◽

Brain Anatomy ◽

High Definition ◽

Direct Current Stimulation

Background: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer’s disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. Objective: To measure the effect of individualized HD-tDCS in AD patients. Methods: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient’s brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. Results: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. Conclusion: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

Download Full-text

Hippocampal Metabolic Subregions and Networks: Behavioral, Molecular and Pathological Aging Profiles

10.21203/rs.3.rs-903896/v1 ◽

2021 ◽

Author(s):

Somayeh Maleki Balajoo ◽

Simon B. Eickhoff ◽

Shahrzad Kharabian Masouleh ◽

Anna Plachti ◽

Laura Waite ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Metabolic Networks ◽

Cortical Atrophy ◽

Healthy Elderly ◽

Cornu Ammonis ◽

Data Driven Approach ◽

Elderly Cohort ◽

Individual Profiles ◽

Local Metabolism

Abstract Purpose: Hippocampal dysfunction happens across many neuropsychiatric disorders and is the hallmark of Alzheimer’s disease with evidenced metabolic alterations. However, while metabolic changes are a key aspect of Alzheimer’s disease, hippocampal metabolic networks, as defined by metabolic covariance, haven’t been identified in healthy populations. As the hippocampus portrays cytoarchitectural, connectional, and functional heterogeneity, heterogeneous patterns of metabolic covariance could be expected. Methods: We first characterized this heterogeneity with a data-driven approach by identifying the spatial pattern of hippocampus differentiation based on metabolic covariance with the rest of the brain in FDG-PET data of large healthy elderly cohort (n=362). Then, we characterized the metabolic networks of the robustly defined subregions. In the following, we characterized the disentangled hippocampal metabolic networks with regards to behavioral and neurotransmitter systems using quantitative decoding. Finally, we examined how the local metabolism in the hippocampal subregions is influenced by Alzheimer’s disease pathology in a cohort of ADNI participants (n = 580). Results: Based on hippocampal-brain metabolic covariance in a healthy elderly cohort, we found a differentiation into primarily anterior vs. posterior and secondarily Cornu Ammonis (CA) vs. subiculum subregions. Characterizing the associated metabolic networks revealed that the anterior-subiculum network including temporal-pole and orbitofrontal regions relates to self, motivation and mentalizing behavior and is influenced by dopaminergic systems. In contrast, the posterior-subiculum shows a wide cortical network engaged in action- and world-oriented cognition targeted by serotoninergic systems. The anterior- and posterior-CA, connected respectively to amygdala and broader subcortical networks, are associated to several transporters release. Local metabolism comparison between Alzheimer’s disease-related diagnosis groups revealed early CA’s alterations while posterior subicular alterations appear at advanced stages in line with broader cortical atrophy and behavioral dysfunctions.Conclusion: Future studies should delineate patients’ individual profiles according to hippocampal subregions and networks.

Download Full-text