Objective:

The objective of this study is to assess the spatial specificity of the tau accumulation pattern in cognitively unimpaired individuals (CU) using independent component analysis (ICA).

Background:

Tau accumulation is a key characteristic of neurodegenerative conditions such as Alzheimer’s Disease (AD). Tau’s pattern of spatial distribution has been shown to link to AD's different clinical manifestations. However, the implications of tau accumulation pattern in different cognitive abilities in CU remains poorly understood.

Design/Methods:

Initially, we analyzed tau positron emission tomography (PET) scans from 590 CU (age 66.58 ± 5.13 years, 340 females) from WCM using ICA to identify diverse tau deposition’s patterns in CU. We then forward applied these patterns to tau PET scans (AV1451 tracer) from 141 CU (mean age 74.69 ± 7.53, 81 female) within the ADNI dataset (Alzheimer's Disease Neuroimaging Initiative). Finally, using multiple linear regression, we assessed the associations between each tau accumulation pattern and cognitive performance, measured by the Mini-Mental State Examination (MMSE) total score and the sub-measures of Alzheimer’s Disease Assessment Scale (ADAS) (i.e., delayed word recall and word recognition), controlling for age and gender as covariates.

Results:

Five different patterns of tau deposition - 1) asymmetric right parietal, 2) asymmetric left frontal-temporoparietal, 3) asymmetric right frontal-temporal, 4) bilateral temporoparietal, and 5) bilateral amygdala-hippocampus - were associated differentially with our cognitive scores. MMSE total score showed a significant association with the patterns 1 and 4 (p<0.05). Delayed word recall was significantly associated with patterns 1,2,3 (p<0.05), and marginally with the pattern 4 and 5 (p<0.07). Finally, word recognition was significantly associated with pattern 5 (P<0.05), and marginally correlated with pattern 2 (p<0.06).

Conclusions:

The study suggests that the pattern of tau in the neocortex can contribute to cognitive decline even in CU. This finding highlights the importance of identifying distinct tau deposition patterns in the early stages of the diseases.