ReviewBrain : a journal of neurology2016
Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit.
Review in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis that pooled it.
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Who cites it
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 388 citations in OpenAlex.
- A co-alteration parceling of the cingulate cortex.Brain structure & function · 2022Pooled it
- Disturbed neurovascular coupling in type 2 diabetes mellitus patients: Evidence from a comprehensive fMRI analysis.NeuroImage. Clinical · 2019Trial
- White matter microstructure and motor function in amnestic mild cognitive impairment and Alzheimer's dementia.Neuroimage. Reports · 2026Article
- Vitamin D binding protein in ventral CA3 of the hippocampus drives stress-induced depression.Science advances · 2026Article
- Structural MRI across lifespan reveals differential thalamic trajectories in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetically linked brain imaging markers of memory decline in aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A NOVEL BAYESIAN FRAMEWORK UNCOVERING BRAIN CONNECTIVITY-TO-SHAPE RELATIONSHIP IN PRECLINICAL ALZHEIMER'S DISEASE.The annals of applied statistics · 2026Article
- Thalamic nuclei insights into Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Maintaining and regaining episodic memory in Alzheimer disease: a circuit-based perspective.Nature reviews. Neurology · 2026Review
- Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.Nature neuroscience · 2026Article
- Neuronal alkaline phosphatase promotes the spread of Tau-induced pathology, and its blockade prevents neurodegeneration and memory loss.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- When Alzheimer's pathology meets cardiometabolic risk: intrinsic subcortical-cortical connectivity signatures of retroactive interference in aging.Alzheimer's research & therapy · 2026Article
- Neural correlates of Parkinson's improvements after combined digital-levodopa therapy: a pilot study.Brain communications · 2026Article
- Distinguishing early from late mild cognitive impairment: a multi-level analysis of regional morphometry and KLS-derived network topology.Frontiers in aging neuroscience · 2026Article
- Atrophy patterns of deep gray matter nuclei in Alzheimer's disease and frontotemporal dementia.Journal of Alzheimer's disease : JAD · 2025Article
- Deep brain stimulation of the anterior nucleus of the thalamus in animal models of mesial temporal lobe epilepsy: A literature review.Epilepsy research · 2025Review
- Long-term efficacy of anterior nucleus of the thalamus deep brain stimulation in drug-resistant epilepsy: a 5-year multicenter study.BMC medicine · 2025Article
- Brain age prediction and early neurodegeneration detection using contrastive learning on brain biomechanics: a retrospective, multicentre study.EBioMedicine · 2025Article
- Targeting the glymphatic system: Aβ accumulation and phototherapy strategies across different stages of Alzheimer's disease.Translational neurodegeneration · 2025Review
- Non-mutated human tau stimulates Alzheimer's disease-relevant neurodegeneration in a microglia-dependent manner.Scientific reports · 2025Article
125 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
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Abstract
It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer's disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer's disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer's disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer's disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer's disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer's disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.