Time course of brain volume changes in the preclinical phase of Alzheimer's disease

Bernard, Charlotte; Helmer, Catherine; Dilharreguy, Bixente; Amieva, Hélène; Auriacombe, Sophie; Dartigues, Jean‐François; Allard, Michèle; Catheline, Gwénaëlle

doi:10.1016/j.jalz.2013.08.279

Cited by 54 publications

(40 citation statements)

References 35 publications

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“…Additionally, the present results are in line with a longitudinal MRI study demonstrating significant atrophy in medial temporal, inferolateral temporal, and parietal lobes and posterior cingulate in families with early-onset AD circa five years before the diagnosis of AD [36], as well as studies with sporadic AD patients which demonstrated atrophy of medial temporal lobe structures four to ten years before the AD diagnosis [37][38][39][40][41].…”

Section: Discussionsupporting

confidence: 90%

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Hirni

Kivisaari

Krumm

et al. 2016

JAD

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Abstract. Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g., semantic object memory impairments) may predate or accompany ERC (i.e., episodic memory) dysfunction in the preclinical course of typical AD. We developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness) using common neuropsychological tests in 31 healthy individuals and 58 early AD patients. These formulae estimated the longitudinal courses of mPRC and ERC functioning in independent groups of 28 optimally healthy individuals who developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC-NC estimated mPRC and ERC functioning at the earliest observation,

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Section: Discussionsupporting

confidence: 90%

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Hirni

Kivisaari

Krumm

et al. 2016

JAD

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“…Longitudinal studies conducted on cohorts of cognitively normal elders have reported that hippocampal atrophy is already present in the preclinical stage, ie before the stage of MCI (Bernard et al, 2014;Smith et al, 2012Smith et al, , 2007, up to 10 years before the diagnosis of dementia (Tondelli et al, 2012).…”

Section: Hippocampal Damage In Ad: Previous Knowledge From Neuropathomentioning

confidence: 99%

Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

2015

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Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vulnerability of hippocampal subfields to AD processes, neuroimaging researchers have tried to capture corresponding morphological changes within the hippocampus. The present review provides an overview of the methodological developments that allow the assessment of hippocampal subfield morphology in vivo, and summarizes the results of studies looking at the effects of AD and normal aging on these structures. Most studies highlighted a focal atrophy of the CA1 subfield in the early (predementia or even preclinical) stages of AD, before atrophy becomes more widespread at the dementia stage, consistent with the pathological literature. Preliminary studies have indicated that looking at this focal atrophy pattern rather than standard whole hippocampus volumetry improves diagnostic accuracy at the mild cognitive impairment (MCI) stage. However, controversies remain regarding changes in hippocampal subfield structure in normal aging and regarding correlations between specific subfield volume and memory abilities, very likely because of the strong methodological variability between studies. Overall, hippocampal subfield analysis has proven to be a promising technique in the study of AD. However, harmonization of segmentation protocols and studies on larger samples are needed to enable accurate comparisons between studies and to confirm the clinical utility of these techniques.

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“…Also, CMBs and WMLs (hyper/hypo-intense signals) and volumetric techniques provide the least information regarding underlying mechanisms or pathology (e.g., gliosis, demyelination, axonal loss). Although it may be possible to detect subtle hippocampal volume changes during early MCI and preclinical phases of AD [19, 154, 175], gross cortical and hippocampal atrophy may not emerge until relatively late in the AD process after observable cognitive decline has occurred [91]. Although DTI metrics offer quantitative indexes of microstructural change, as with other structural imaging modalities, a given change in DTI metrics may reflect a number of different microstructural changes, thus limiting the clinical utility of these scales.…”

Section: Clinical Utilitymentioning

confidence: 99%

Brain imaging of neurovascular dysfunction in Alzheimer’s disease

et al. 2016

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Neurovascular dysfunction, including blood–brain barrier (BBB) breakdown and cerebral blood flow (CBF) dysregulation and reduction, are increasingly recognized to contribute to Alzheimer’s disease (AD). The spatial and temporal relationships between different pathophysiological events during preclinical stages of AD, including cerebrovascular dysfunction and pathology, amyloid and tau pathology, and brain structural and functional changes remain, however, still unclear. Recent advances in neuroimaging techniques, i.e., magnetic resonance imaging (MRI) and positron emission tomography (PET), offer new possibilities to understand how the human brain works in health and disease. This includes methods to detect subtle regional changes in the cerebrovascular system integrity. Here, we focus on the neurovascular imaging techniques to evaluate regional BBB permeability (dynamic contrast-enhanced MRI), regional CBF changes (arterial spin labeling- and functional-MRI), vascular pathology (structural MRI), and cerebral metabolism (PET) in the living human brain, and examine how they can inform about neurovascular dysfunction and vascular pathophysiology in dementia and AD. Altogether, these neuroimaging approaches will continue to elucidate the spatio-temporal progression of vascular and neurodegenerative processes in dementia and AD and how they relate to each other.

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Time course of brain volume changes in the preclinical phase of Alzheimer's disease

Abstract: Incident AD cases present mediotemporal lesions up to 5 years before diagnosis. This neurodegenerative process seems to progressively reach the temporoparietal cortices in the AD preclinical phase.

Cited by 54 publications

References 35 publications

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

Brain imaging of neurovascular dysfunction in Alzheimer’s disease

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