Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve

Purpose: Cerebral atrophy measured by Magnetic Resonance structural Imaging has been proposed as a surrogate marker to improve the early diagnosis of Alzheimer's Disease (AD). More precisely, it could be a useful tool to distinguish Mild Cognitive Impairment (MCI) subjects who will effectively convert to AD from those who will remain at the MCI stage. However, studies on large samples are still required to determine cerebral atrophy's practical interest at the individual level, especially with regards to its capacity to disentangle the confounding role of cognitive reserve.

Materials and Methods: One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 AD patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 MCI subjects had converted to Alzheimer's disease (referred to as progressive MCI or pMCI, as opposed to stable MCI or sMCI). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a Normalized Thickness Index (NTI) was computed for each subject, reflecting the position of the subject on the continuum between healthy stage and AD stage. We tested the ability of NTI to predict evolution from MCI to AD at the individual level and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the NTI, the education level and the timeline of conversion to Alzheimer's disease.

Results: NTI at baseline correctly distinguished AD patients from healthy controls with an 85% cross-validated accuracy. NTI also correctly predicted evolution to AD for 76% of MCI subjects after cross-validation, thus showing an advantage over cognitive scores (range 63–72%). Moreover, pMCI subjects who converted later than 1 year after baseline showed a significantly higher education level than those who converted earlier than 1 year after baseline. Finally, subjects with education level above 15 years showed a similar cognitive level as those with an education level below 15 years (p=0.15) while having a more pronounced atrophy as measured by the NTI (p=0.002).

Conclusion: As cerebral atrophy measured by the NTI is less affected than cognitive scores by the confounding role of cognitive reserve, it could be a strong surrogate marker for the early diagnosis of AD, especially for highly educated subjects, up to 24 months before clinical criteria for AD diagnosis are met.