The topography of grey matter involvement in early and late onset Alzheimer's disease

Frisoni, Giovanni B.; Pievani, Michela; Testa, Cristina; Sabattoli, Francesca; Bresciani, Lorenzo; Bonetti, Matteo; Beltramello, Alberto; Hayashi, Kiralee M.; Toga, Arthur W.; Thompson, Paul M.

doi:10.1093/brain/awl377

Cited by 397 publications

(320 citation statements)

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“…Moreover, we have not addressed the impact on diagnostic confidence of important modifiers such as age at onset of cognitive disturbances, APOE genotype and co-morbidities, factors that can alter the certainty of the diagnosis. It is known that early onset patients with dementia (before age 65) have greater change of biomarkers than late onset patients [45,46].…”

Section: Discussionmentioning

confidence: 99%

The use of biomarkers for the etiologic diagnosis of MCI in Europe: An EADC survey

Bocchetta

Galluzzi

Kehoe

et al. 2014

Alzheimer's & Dementia

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We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Ab42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75% of the 37 responders reported using it "always/ frequently") followed by CSF markers (22%), FDG-PET (16%), and amyloid-PET (3%). Only 45% of responders perceive MTA as contributing to diagnostic confidence, where the contribution was rated as "moderate". Seventy-nine percent of responders felt "very/extremely" comfortable delivering a diagnosis of MCI due to AD when both amyloid and neuronal injury biomarkers were abnormal (P , .02 versus any individual biomarker). Responders largely agreed that a combination of amyloidosis and neuronal injury biomarkers was a strongly indicative AD signature.

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Section: Discussionmentioning

confidence: 99%

The use of biomarkers for the etiologic diagnosis of MCI in Europe: An EADC survey

Bocchetta

Galluzzi

Kehoe

et al. 2014

Alzheimer's & Dementia

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Section: Discussionmentioning

confidence: 99%

“…Two regions of reduced blood flow were also measured, namely the posterior cingulate and a fairly extended area in the left parietal and parieto-temporal cortex. Most of these regions are known to be affected by AD (Ardekani et al, 2007;Chetelat et al, 2002;Convit et al, 1997;Dickerson et al, 2001;Firbank et al, 2007;Fox and Schott, 2004;Fox et al, 1996b;Frisoni et al, 2007;Ishii et al, 2005a;Jack et al, 1999;Karas et al, 2007;Killiany et al, 2000;Krasuski et al, 1998;Matsuda et al, 2002;Pantano et al, 1999;Pennanen et al, 2005b;Thompson et al, 2007); however, it is their combination via high-dimensional pattern classification that leads to high diagnostic accuracy on an individual basis.The pattern of reduced blood flow measured in our study was asymmetric, and in agreement with the findings of (Minoshima et al, 1994b;Reiman et al, 1996b;Scarmeas et al, 2004) who used PET 15 O imaging in an AD sample. A variety of PET studies in AD have demonstrated asymmetrically reduced blood flow or metabolic activity in AD patients (Foster et al, 1983;Ishii et al, 2005b;Kawachi et al, 2006;Koss et al, 1985;Martin et al, 1986) and in elderly individuals with cognitive decline (Hunt et al, 2007); however the biological underpinnings of these asymmetries are not quite known.…”

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Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

et al. 2008

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This work builds upon previous studies that reported high sensitivity and specificity in classifying individuals with mild cognitive impairment (MCI), which is often a prodromal phase of Alzheimer's Disease (AD), via pattern classification of MRI scans. The current study integrates MRI and PET 15 O water scans from 30 participants in the Baltimore Longitudinal Study of Aging, and tests the hypothesis that joint evaluation of structure and function can yield higher classification accuracy than either alone. Classification rates of up to 100% accuracy were achieved via leave-one-out cross validation, whereas conservative estimates of generalization performance in new scans, evaluated via bagging cross-validation, yielded an area under the receiver operating characteristic (ROC) curve equal to 0.978 (97.8%), indicating excellent diagnostic accuracy. Spatial maps of regions determined to contribute the most to the classification implicated many temporal, prefrontal, orbitofrontal, and parietal regions. Detecting complex patterns of brain abnormality in early stages of cognitive impairment has pivotal importance for the detection and management of AD. KeywordsAlzheimer's Disease; MCI; high-dimensional Pattern Classification; MRI; PET; voxel-based analysis; diagnosis of AD Amnestic mild cognitive impairment (MCI) is often a prodromal stage to Alzheimer's Disease (AD), as individuals with MCI may convert to AD at an annual rate as high as 15% . Therefore, MCI is frequently considered to be a good target for early AD diagnosis, and for therapeutic interventions. MRI and PET imaging can potentially be used as diagnostic tools that assess brain structure and function in a direct and objective way and have potential utility for diagnosis, prognosis, and evaluation of disease progression and treatment effects.Many imaging studies have found loss of grey matter (GM) and metabolic abnormalities in MCI. Most of the earlier studies were based on volumetric measurements of regions of interest (ROI's) (Chetelat et al., 2002;Convit et al., 2000;Dickerson et al., 2001;Fox et al., 1996a;Kaye et al., 1997;Killiany et al., 2000), such as the hippocampus and the entorhinal cortex, and have confirmed GM atrophy in regions that are known to be affected by AD. However, the pattern of AD pathology is complex and evolves as the disease progresses, starting mainly in the hippocampus and entorhinal cortex, and subsequently spreading throughout temporal and orbitofrontal cortex, posterior cingulate, and association cortex generally (Braak et al., 1998). Therefore, measuring volumes or average PET signals of a few structures cannot capture Voxel-based morphometry (VBM) has been proposed by a number of investigators as a more comprehensive way of measuring the spatial distribution of brain atrophy in MCI and AD, by evaluating images region by region instead of making a priori assumptions about specific ROIs. A variety of VBM-type methods exist (Ashburner and Friston, 2000;Chung et al., 2001;Davatzikos et al., 2001;Davatzikos et al., 1996...

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“…The subgroups of AD patients were classified based on a determined cut-off of 65 years of age at onset, based on previous studies comparing features of EOAD and LOAD patients (Kemp et al, 2003;Kim et al, 2005;Shiino et al, 2006;Frisoni et al, 2007;Rabinovici et al, 2010;Canu et al, 2012;Sa et al, 2012;Smits et al, 2012;Cho et al, 2013), as well as on clinical grounds (Amaducci et al, 1986). This cut-off is also used in the DSM-IV TR nomenclature to specify subtypes (American Psychiatric Association, 2000).…”

Section: Subjectsmentioning

confidence: 99%

Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment

Joubert

Gour

Guedj

et al. 2016

Cortex

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The goal of this study was to investigate the specific patterns of memory breakdown in patients suffering from early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Twenty EOAD patients, twenty LOAD patients, twenty matched younger controls, and twenty matched older controls participated in this study.All participants underwent a detailed neuropsychological assessment, an MRI scan, an FDG-PET scan, and AD patients had biomarkers as supporting evidence of both amyloïdopathy and neuronal injury. Results of the neuropsychological assessment showed that both EOAD and LOAD groups were impaired in the domains of memory, executive functions, language, praxis, and visuoconstructional abilities, when compared to their respective control groups. EOAD and LOAD groups, however, showed distinct patterns of memory impairment. Even though both groups were similarly affected on measures of episodic, short term and working memory, in contrast semantic memory was significantly more impaired in LOAD than in EOAD patients. The EOAD group was not more affected than the LOAD group in any memory domain. EOAD patients, however, showed significantly poorer performance in other cognitive domains including executive functions and visuoconstructional abilities. A more detailed analysis of the pattern of semantic memory performance among patient groups revealed that the LOAD was more profoundly impaired, in tasks of both spontaneous recall and semantic recognition.Voxel-Based Morphometry (VBM) analyses showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe region, while PET-FDG analyses revealed that poorer semantic performance was associated with greater hypometabolism in the left temporoparietal region, both areas reflecting key regions of the semantic network. Results of this study indicate that EOAD and LOAD patients present with distinct patterns of memory impairment, and that a genuine semantic impairment may represent one of the clinical hallmarks of LOAD.

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The topography of grey matter involvement in early and late onset Alzheimer's disease

Cited by 397 publications

References 63 publications

The use of biomarkers for the etiologic diagnosis of MCI in Europe: An EADC survey

The use of biomarkers for the etiologic diagnosis of MCI in Europe: An EADC survey

Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment

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