The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals

Abstract

Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This “disease signature” approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.

Structural MRI Biomarkers Related to Cognitive Recovery and Resistance to Recovery Using the Penalized Mixture Cure Model

“…These results are consistent with recent findings ( Williams et al, 2023 ) indicating that increased cortical thickness or volume in certain regions may not always be protective. Instead, these features may reflect maladaptive neuroplasticity or pathological processes such as neuroinflammation or tau pathology, which are associated with slower recovery rates ( Dickerson et al, 2009 ). The frontal pole and transverse temporal regions are involved in higher-order cognitive functions such as decision-making and auditory processing, and alterations in these regions may signal early disruptions in the brain’s compensatory capacity, preventing successful cognitive recovery.…”

Structural MRI Biomarkers Related to Cognitive Recovery and Resistance to Recovery Using the Penalized Mixture Cure Model

“…These results are consistent with recent findings ( Williams et al, 2023 ) indicating that increased cortical thickness or volume in certain regions may not always be protective. Instead, these features may reflect maladaptive neuroplasticity or pathological processes such as neuroinflammation or tau pathology, which are associated with slower recovery rates ( Dickerson et al, 2009 ). The frontal pole and transverse temporal regions are involved in higher-order cognitive functions such as decision-making and auditory processing, and alterations in these regions may signal early disruptions in the brain’s compensatory capacity, preventing successful cognitive recovery.…”

Neuro-degeneration profile of Alzheimer's patients: A brain morphometry study

“…One fact that may explain the discrepancies between our results and those reported in literature ( Blanc et al, 2015 , Clerx et al, 2013 , Dickerson et al, 2009 , Lerch, 2004 , O'Brien et al, 2014 ) are the number of images acquired and processing method used. Dickerson et al (2009) acquired multiple images (n = 4) of the same patient to improve the contrast–to-noise ratio and the quality of segmentation ( Dickerson et al, 2009 ). For the segmentation of a single image, Blanck and collaborators corrected manually the segmentation of 25% of the subjects ( Blanc et al, 2015 ).…”

Differences in Cortical Thickness in Healthy Controls, Subjects with Mild Cognitive Impairment, and Alzheimer's Disease Patients: A Longitudinal Study

“…However, in our study, thinner cortex was associated with worse cognitive performance in large areas of the frontal and temporal cortices of the AD subjects. Some studies have also reported a correlation between CDR-SB and CTH [13,14,40], which could not be found in our HC or MCI groups. Unfortunately the CDR-SB scores were not available for the subjects with AD.…”

Structural MRI Biomarkers Related to Cognitive Recovery and Resistance to Recovery Using the Penalized Mixture Cure Model

“…These results are consistent with recent findings ( Williams et al, 2023 ) indicating that increased cortical thickness or volume in certain regions may not always be protective. Instead, these features may reflect maladaptive neuroplasticity or pathological processes such as neuroinflammation or tau pathology, which are associated with slower recovery rates ( Dickerson et al, 2009 ). The frontal pole and transverse temporal regions are involved in higher-order cognitive functions such as decision-making and auditory processing, and alterations in these regions may signal early disruptions in the brain’s compensatory capacity, preventing successful cognitive recovery.…”

Neuro-degeneration profile of Alzheimer's patients: A brain morphometry study

“…One fact that may explain the discrepancies between our results and those reported in literature ( Blanc et al, 2015 , Clerx et al, 2013 , Dickerson et al, 2009 , Lerch, 2004 , O'Brien et al, 2014 ) are the number of images acquired and processing method used. Dickerson et al (2009) acquired multiple images (n = 4) of the same patient to improve the contrast–to-noise ratio and the quality of segmentation ( Dickerson et al, 2009 ). For the segmentation of a single image, Blanck and collaborators corrected manually the segmentation of 25% of the subjects ( Blanc et al, 2015 ).…”

Differences in Cortical Thickness in Healthy Controls, Subjects with Mild Cognitive Impairment, and Alzheimer's Disease Patients: A Longitudinal Study

“…However, in our study, thinner cortex was associated with worse cognitive performance in large areas of the frontal and temporal cortices of the AD subjects. Some studies have also reported a correlation between CDR-SB and CTH [13,14,40], which could not be found in our HC or MCI groups. Unfortunately the CDR-SB scores were not available for the subjects with AD.…”

Structural MRI Biomarkers Related to Cognitive Recovery and Resistance to Recovery Using the Penalized Mixture Cure Model

“…These results are consistent with recent findings ( Williams et al, 2023 ) indicating that increased cortical thickness or volume in certain regions may not always be protective. Instead, these features may reflect maladaptive neuroplasticity or pathological processes such as neuroinflammation or tau pathology, which are associated with slower recovery rates ( Dickerson et al, 2009 ). The frontal pole and transverse temporal regions are involved in higher-order cognitive functions such as decision-making and auditory processing, and alterations in these regions may signal early disruptions in the brain’s compensatory capacity, preventing successful cognitive recovery.…”

Neuro-degeneration profile of Alzheimer's patients: A brain morphometry study

“…One fact that may explain the discrepancies between our results and those reported in literature ( Blanc et al, 2015 , Clerx et al, 2013 , Dickerson et al, 2009 , Lerch, 2004 , O'Brien et al, 2014 ) are the number of images acquired and processing method used. Dickerson et al (2009) acquired multiple images (n = 4) of the same patient to improve the contrast–to-noise ratio and the quality of segmentation ( Dickerson et al, 2009 ). For the segmentation of a single image, Blanck and collaborators corrected manually the segmentation of 25% of the subjects ( Blanc et al, 2015 ).…”

Differences in Cortical Thickness in Healthy Controls, Subjects with Mild Cognitive Impairment, and Alzheimer's Disease Patients: A Longitudinal Study

“…However, in our study, thinner cortex was associated with worse cognitive performance in large areas of the frontal and temporal cortices of the AD subjects. Some studies have also reported a correlation between CDR-SB and CTH [13,14,40], which could not be found in our HC or MCI groups. Unfortunately the CDR-SB scores were not available for the subjects with AD.…”