Cognitively Preserved Subjects with Transitional Cerebrospinal Fluid ß-Amyloid 1-42 Values Have Thicker Cortex in Alzheimer's Disease Vulnerable Areas

Fortea, Juan; Sala‐Llonch, Roser; Bartrés‐Faz, David; Lladó, Albert; Solé‐Padullés, Cristina; Bosch, Beatríz; Antonell, Anna; Olives, Jaume; Sánchez‐Valle, Raquel; Molinuevo, José Luís; Rami, Lorena

doi:10.1016/j.biopsych.2011.02.017

Cited by 94 publications

(83 citation statements)

References 43 publications

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“…For instance, four papers have interpreted the above-described Aβ-atrophy correlations in the cognitively healthy as indications of early AD [3,[95][96][97] and that the results support or are in accordance with the amyloid hypothesis. Thus, the same results are taken to support radically opposing views.…”

Section: Atrophy Amyloid and Cognition In Nondemented Elderlymentioning

confidence: 66%

“…4c, d, but the results are binarized and corrected for multiple comparisons across space (FDR<0.05). e Fortea et al [95] correlated CSF Aβ42 with cortical thickness in a group of healthy elderly and patients with subjective MCI (sMCI). The relationships found in this mixed cohort were spatially restricted, but included an area overlapping the entorhinal cortex.…”

Section: Studies Of Amyloid Imaging and Atrophymentioning

confidence: 98%

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Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised

Fjell

Walhovd

2011

Mol Neurobiol

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Huge progress has been made in unraveling the mysteries of Alzheimer's disease (AD), but we still do not understand the basic mechanisms that set off the cascade of pathological events. In May 2011, the National Institute on Aging-Alzheimer's Association published new diagnostic guidelines, expected to have huge impact on AD research and clinical practice. However, the new guidelines are already criticized for being biased in favor of a specific theory of the pathophysiological origins of AD-the amyloid cascade hypothesis. Shortly before publication of the guidelines, a hypothetical model of the dynamic biomarkers of the Alzheimer's pathological cascade was published, taking as starting point that biomarkers reflecting brain levels of amyloid become deviant long before brain atrophy, cognitive dysfunction, or clinical symptoms are manifest. This model has already attracted substantial interest and arguably represents a dominating view within human research on AD. Here we critically review the evidence for the view of amyloid as an initiating event in the pathological cascade and discuss how central assumptions of this hypothesis affect how results from contemporary human AD research are understood. Interpretations of new results are greatly impacted by researchers' view on the role of amyloid, and identical observations are sometimes taken to support radically opposing views on the amyloid hypothesis. We argue that the canonical view of the role of amyloid as the main causal factor in AD may not be correct and that evidence from recent neuroimaging studies indicates that amyloid is neither necessary nor sufficient, for the manifestation of AD-like brain atrophy.

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Section: Atrophy Amyloid and Cognition In Nondemented Elderlymentioning

confidence: 66%

Section: Studies Of Amyloid Imaging and Atrophymentioning

confidence: 98%

Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised

Fjell

Walhovd

2011

Mol Neurobiol

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“…First, in sporadic AD, some studies have found increased regional volume and thickness in healthy subjects with evidence of initial beta-amyloid deposition (Chételat et al, 2010;Fortea et al, 2011;Johnson et al, 2014). Studies with subjects at-risk of AD carrying the APOE ε4 allele (Espeseth et al, 2012;Fortea et al, 2014) have also reported areas of cortical thickening before cortical atrophy.…”

Section: Discussionmentioning

confidence: 95%

Evolving brain structural changes in PSEN1 mutation carriers

Sala‐Llonch

Lladó

Fortea

et al. 2015

Neurobiology of Aging

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“…Similarly, Dor e and colleagues [11] found that an increase in Ab accumulation was associated with decreased cortical thickness in the posterior cingulate, precuneus, and hippocampus among CN individuals. Other studies using cerebrospinal fluid (CSF) biomarkers for Ab have found similar associations between Ab aggregation and structural brain changes in ADsusceptible regions [12]. Relatedly, although AD is characterized by a decline in cognition [1], the extent to which Ab accumulation correlates with cognition among CN individuals is yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 96%

O1‐12‐02: Amyloid Burden, Cortical Thickness, and Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention

Doherty

Oh²,

Schultz

et al. 2014

Alzheimer's & Dementia

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There is a growing interest in understanding how amyloid b (Ab) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively normal (CN) individuals. Therefore, not much is known about the associations between Ab burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late to middle-aged adults (mean age 5 60.72 6 5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive examination. Blinded visual rating of the PiB scans was used to classify the participants as Ab1 or Ab2. Cortical thickness measurements were derived from the MR images. The Ab1 group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Ab2 group. The Ab1 group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Ab aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Ab deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

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Cognitively Preserved Subjects with Transitional Cerebrospinal Fluid ß-Amyloid 1-42 Values Have Thicker Cortex in Alzheimer's Disease Vulnerable Areas

Cited by 94 publications

References 43 publications

Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised

Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised

Evolving brain structural changes in PSEN1 mutation carriers

O1‐12‐02: Amyloid Burden, Cortical Thickness, and Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention

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