Longitudinal brain metabolic changes from amnestic Mild Cognitive Impairment to Alzheimer's disease

Fouquet, Marine; Desgranges, Béatrice; Landeau, Brigitte; Duchesnay, Édouard; Mézenge, Florence; Sayette, Vincent de La; Viader, Fausto; Baron, JC; Eustache, Francis; Chételat, Gaël

doi:10.1016/s1053-8119(09)71030-4

Cited by 20 publications

(25 citation statements)

References 33 publications

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“…These results support previous studies showing that grey matter loss in the anterior cingulate and medial frontal cortex regions are among the most predictive structural brain changes of progression from MCI to AD [6,42,50,51]. Interestingly, there is also evidence of metabolic decreases and amyloid-␤ deposition in the anterior cingulate and frontal regions in prodromal stages of AD [52][53][54][55], suggesting a specific progression of the neurodegenerative process in these brain regions for individuals with progressive MCI. Although the role of the anterior cingulate gyrus remains equivocal, this region has been proposed to be part of an executive control network that ensure conflict detection and selection of coordinated goal-directed behavior [56,57].…”

Section: Discussionsupporting

confidence: 90%

Predicting Progression to Dementia in Elderly Subjects with Mild Cognitive Impairment Using Both Cognitive and Neuroimaging Predictors

Peters

Villeneuve

Belleville

2013

JAD

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The objective of this work was to assess the predictive accuracy of targeted neuroimaging and neuropsychological measures for the detection of incipient dementia in individuals with mild cognitive impairment (MCI), and to examine the potential benefit of combining both classes of measures. Baseline MRI measures included hippocampal volume, cortical thickness, and white matter hyperintensities. Neuropsychological assessment focused on different aspects of episodic memory (i.e., familiarity, free recall, and associative memory) and executive control functions (i.e., working memory, switching, and planning). Global and regional cortical thinning was observed in MCI patients who progressed to dementia compared to those who remained stable, whereas no differences were found between groups for baseline hippocampal volume and white matter hyperintensities. The strongest neuroimaging predictors were baseline cortical thickness in the right anterior cingulate and middle frontal gyri. For cognitive predictors, we found that deficits in both free recall and recognition episodic memory tasks were highly suggestive of progression to dementia. Cortical thinning in the right anterior cingulate gyrus, combined to controlled and familiarity-based retrieval deficits, achieved a classification accuracy of 87.5%, a specificity of 90.9%, and a sensitivity of 83.3%. This predictive model including both classes of measures provided more accurate predictions than those based on neuroimaging or cognitive measures alone. Overall, our findings suggest that detecting preclinical Alzheimer's disease is probably best accomplished by combining complementary information from targeted neuroimaging and cognitive classifiers, and highlight the importance of taking into account both structural and functional changes associated with the disease.

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Section: Discussionsupporting

confidence: 90%

Predicting Progression to Dementia in Elderly Subjects with Mild Cognitive Impairment Using Both Cognitive and Neuroimaging Predictors

Peters

Villeneuve

Belleville

2013

JAD

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“…A key observation is that the joint presence of brain injury and β‐amyloidosis appears to be necessary for the development of overt cognitive impairment in what becomes AD dementia, consistent with our own observations and those of others . Furthermore, because AD dementia is associated with more rapid brain atrophy and glucose hypometabolism than mild cognitive impairment due to AD or preclinical AD in cognitively normal persons, it is possible that once certain levels of brain injury and β‐amyloidosis are reached, possibly independently initially, an interaction of the 2 occurs and acceleration of brain injury results. Others have also come to a similar conclusion .…”

Section: Discussionsupporting

confidence: 87%

Brain injury biomarkers are not dependent on β‐amyloid in normal elderly

Knopman

Jack

Wiste

et al. 2013

Annals of Neurology

168

138

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Background The new criteria for preclinical Alzheimer’s Disease (AD) proposed 3 stages: abnormal levels of β-amyloid (stage 1); stage 1 plus evidence of brain injury (stage 2); and stage 2 plus subtle cognitive changes (stage 3). However, a large group of subjects with normal β-amyloid biomarkers have evidence of brain injury; we labeled them as “suspected non-Alzheimer pathway” (sNAP) group. The characteristics of the sNAP group are poorly understood. Methods Using the preclinical AD classification, 430 cognitively normal subjects from the Mayo Clinic Study of Aging who underwent brain MR, 18fluorodeoxyglucose (FDG) and Pittsburgh compound B (PiB) positron emission tomography (PET) were evaluated with FDG PET regional volumetrics, MR regional brain volumetrics, white matter hyperintensity (WMH) volume and number of infarcts. We examined cross-sectional associations across AD preclinical stages, those with all biomarkers normal, and the sNAP group. Results The sNAP group had a lower proportion (14%) with APOE ε4 genotype than the preclinical AD stages 2 + 3. The sNAP group did not show any group differences compared to stages 2 + 3 of the preclinical AD group on measures of FDG PET regional hypometabolism, MR regional brain volume loss, cerebrovascular imaging lesions, vascular risk factors, imaging changes associated with α-synucleinopathy or physical findings of parkinsonism. Conclusions Cognitively normal persons with brain injury biomarker abnormalities, with or without abnormal levels of β-amyloid, were indistinguishable on a variety of imaging markers, clinical features and risk factors. The initial appearance of brain injury biomarkers that occurs in cognitively normal persons with preclinical AD may not depend on β-amyloidosis.

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“…The evolution of brain atrophy from MCI to AD parallels the pattern of tau deposition from the medial temporal to lateral temporal and parietal cortices 50 . Deficits in cognition are better explained by changes in glucose metabolism and atrophy than by the deposition of Aβ [51][52][53][54][55] . Studies examining the relationships between Aβ and both glucose metabolism and atrophy have discovered associations ranging from absent to moderately strong 47,[56][57][58][59][60] .…”

Section: Late-onset Admentioning

confidence: 99%

Imaging the evolution and pathophysiology of Alzheimer disease

2018

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Technologies for imaging the pathophysiology of Alzheimer disease (AD) now permit studies of the relationships between the two major proteins deposited in this disease-amyloid-β (Aβ) and tau-and their effects on measures of neurodegeneration and cognition in humans. Deposition of Aβ in the medial parietal cortex appears to be the first stage in the development of AD, although tau aggregates in the medial temporal lobe (MTL) precede Aβ deposition in cognitively healthy older people. Whether aggregation of tau in the MTL is the first stage in AD or a fairly benign phenomenon that may be transformed and spread in the presence of Aβ is a major unresolved question. Despite a strong link between Aβ and tau, the relationship between Aβ and neurodegeneration is weak; rather, it is tau that is associated with brain atrophy and hypometabolism, which, in turn, are related to cognition. Although there is support for an interaction between Aβ and tau resulting in neurodegeneration that leads to dementia, the unknown nature of this interaction, the strikingly different patterns of brain Aβ and tau deposition and the appearance of neurodegeneration in the absence of Aβ and tau are challenges to this model that ultimately must be explained. Multimodal imaging technologies have transformed research on human ageing and dementia by enabling the investigation of complex interrelated mechanisms that underlie the development of Alzheimer disease (AD). The two aggregated proteins implicated in the pathogenesis of AD-amyloid-β (Aβ) and tau-can be visualized with positron emission tomography (PET), and the proposed downstream consequence of neurodegeneration can be examined with structural MRI, functional MRI and glucose metabolism PET. Studies of cognitively healthy older people and those with cognitive impairment or dementia have partially elucidated these pathophysiological processes in an approach that could be a model for the investigation of many degenerative neurological diseases.

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Longitudinal brain metabolic changes from amnestic Mild Cognitive Impairment to Alzheimer's disease

Cited by 20 publications

References 33 publications

Predicting Progression to Dementia in Elderly Subjects with Mild Cognitive Impairment Using Both Cognitive and Neuroimaging Predictors

Predicting Progression to Dementia in Elderly Subjects with Mild Cognitive Impairment Using Both Cognitive and Neuroimaging Predictors

Brain injury biomarkers are not dependent on β‐amyloid in normal elderly

Imaging the evolution and pathophysiology of Alzheimer disease

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