Fazekas scale magnetic resonance imaging assessment in Alzheimer's disease and primary age-related tauopathy

Abstract

Background: Brain vascular pathology is an important comorbidity in Alzheimer's disease (AD), with white matter damage independently predicting cognitive impairment. However, it is still unknown how vascular pathology differentially impacts primary age-related tauopathy (PART) compared to AD. Therefore, our objectives were to compare the brain microangiopathic burden in patients with PART and AD, evaluated by MRI, while assessing its relation with neuropathological findings, patterns of brain atrophy and degree of clinical impairment.

Methods: Clinical information, brain MRI (T1 and T2-FLAIR) and neuropathological data were obtained from the National Alzheimer's Coordinating Centre ongoing study, with a total sample of 167 patients identified, that were divided according to the presence of neuritic plaques in Consortium to Establish a Registry for Alzheimer's disease (CERAD) 0 to 3. Microangiopathic burden and brain atrophy were evaluated by two certified neuroradiologists, using, respectively, the Fazekas score and previously validated visual rating scales to assess brain regional atrophy.

Results: Significant correlations were found between the Fazekas score and atrophy in the fronto-insular and medial temporal regions on both groups, with PART showing overall stronger positive correlations than in AD, especially in the fronto-insular region. For this specific cohort, no significant correlations were found between the Fazekas score and the degree of clinical impairment.

Conclusion: Our results show that PART presents different pathological consequences at the brain microvascular level compared with AD and further supports PART as an independent pathological entity from AD.

Keywords: AD = Alzheimer’s disease; CERAD = Consortium to Establish a Registry for Alzheimer’s disease; PART = Primary age-related tauopathy.

Fig. 1

Representative case of a 91 year-old male patient with AD. (a) Coronal reformat of a 3D T1-weighted sequence shows severe widening of the choroid fissures and severe enlargement of the temporal horns, with marked atrophy of both hippocampi (medial temporal lobe atrophy – MTA – score of 4). (b) Axial T2-FLAIR sequence reveals hyperintensities involving the periventricular and the deep white matter, with irregular periventricular signal extending to the deep white matter in the former and severe confluence in the latter (periventricular and deep Fazekas score of 3)

Fig. 2

No significant differences were found in the Fazekas grading between patients with PART and AD. Uncorrected (a, b) and standardized residuals for age and Braak (c, d) for deep and periventricular Fazekas scores among patients with absence (i.e. PART) or presence (i.e. AD) of neocortical neuritic plaques after neuropathological evaluation. * p < 0.05. ‘ns’ represents non-significant differences between groups

Fig. 3

Correlation analysis between relative regional brain atrophy and Fazekas scores, corrected for age, shows differential patterns in AD and PART. Pearson correlation analysis of relative brain atrophy residuals after linear regression with age per region versus Fazekas scores (periventricular and deep) among 2 groups of participants, distributed according to the absence (i.e. PART) or presence (i.e. AD) of neocortical neuritic plaques after neuropathological evaluation. The regions evaluated are anterior cingulate (AC), orbito-frontal (OF), fronto-insular (FI), medial temporal (MTA) and posterior (Post). Only showing pairs with p < 0.05 in the correlational analysis. Color indicates R Pearson coefficient