A longitudinal observation of brain structure between AD and FTLD

Highlights

• A longitudinal observation of brain structure of AD and FTLD.

• Comparison of brain structure between AD and FTLD.

• Exploring the mechanism and characteristic of AD and FTLD by analyzing the change of brain structure.

Abstract

Introduction

Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) are the leading causes of dementia. To better understand the disease development of cognitive function and anatomical structure in AD and FTLD, we analyzed the changes in brain volume by MRI and the psychological test results. Here, we report a dynamic observation of brain structure.

Methods

Thirteen patients diagnosed with probable AD by the 2011 NIA-AA criteria and eight FTLD patients diagnosed by the FTLD criteria underwent MRI at baseline. All subjects were rescanned after 5 months to 3 years of follow-up. The anatomic changes on T1-weighted imaging of each subject were measured, and the separate changes in the two groups and the differences in the changes between AD and FTLD were analyzed.

Results

In AD patients, the anterior and posterior horns of the lateral ventricle and lateral fissure enlarged progressively (p < 0.001). The volume of the regions, including the medial and lateral temporal lobe, especially the parahippocampal gyrus, and the frontal lobe decreased significantly as the disease progressed (p < 0.001). Additionally, the volume of white matter in the frontal, parietal, temporal lobe and cerebellum decreased in a relatively symmetric pattern (p < 0.001). In FTLD patients, the anterior horn of the lateral ventricle, lateral fissure, cerebral longitudinal fissure, external space of the orbitofrontal cortex, and mesencephalon surrounding the cisterna were enlarged (p < 0.005), while regions including the left frontal lobe, anterior cingulate cortex, basal ganglia (especially the left basal ganglia), left lateral temporal lobe and inferior cerebellar vermis decreased as the disease progressed (p < 0.005). Regarding the differences between AD and FTLD, atrophy of the frontal lobe and bilateral basal ganglia was more significant in FTLD than in AD (p < 0.01). In addition, enlargements of the anterior horn of the lateral ventricle, left lateral fissure and interpeduncular cistern were more significant in FTLD patients than in AD patients (p < 0.01).

Conclusions

These findings suggest that AD and FTLD have distinctly different atrophy patterns: AD patients show diffuse atrophy while FTLD patients show an asymmetrical focal atrophy pattern, which might explain the relatively better and longer preservation of daily living function in FTLD patients.

Introduction

Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) are the leading causes of dementia [1]. Symptoms of AD and FTLD are heterogeneous and can overlap, leading to a high misdiagnosis rate. For accurate differentiation, previous clinical and research criteria both emphasized the diagnostic strength of biomarkers, which included structural magnetic resonance imaging (MRI). Brain atrophy on MRI is the macroscopic manifestation of microscopic neurodegenerative changes, reflecting the cumulative loss of neurons, synapses, and dendritic arborization. [2], [3].

Previous studies have already suggested that AD and FTLD show distinct brain atrophy patterns. Although the atrophy pattern of AD remains controversial due to the various results from different cohorts, studies based on autopsy subjects found that AD patients show atrophy in a relatively diffuse and symmetric pattern, with most atrophy predominant in the bilateral medial temporal lobes, posterior cingulate cortex, precuneus and temporoparietal association regions [4], [5], [6]. FTLD patients show atrophy most predominantly in the frontal and anterior temporal lobes [7]. Additionally, it has already been recognized that AD and FTLD show different cognitive domain involvement, and FTLD patients maintain a relatively better reservation of daily living function for a longer time. In summary, it has been generally accepted that AD and FTLD progress in different patterns with characteristic cognitive domains affected by specific anatomical changes in the brain.

Therefore, based on the previous evidence, we hypothesized that AD patients show brain atrophy in a more diffuse way, while FTLD patients show relatively limited regional brain atrophy so that their functional networks are relatively preserved, which might explain their better preservation of daily living function. Therefore, we analyzed the changes in brain volume on MRI and psychological test results. Here, we report longitudinal observations of brain structure.

To accurately analyze the anatomical changes between the diseases, we applied automated methods to reach an objective result. Nonlinear registration of serial MRI scans provides a means of modeling changes over the whole brain. Repeat scans can be matched onto baseline images by using voxel-level deformation fields estimated using nonlinear image registration algorithms [12]. Using nonlinear image registration algorithms, Jacobian determinants could be computed to quantify the longitudinal volume changes of individual subjects at a voxel level. We used this technique to investigate longitudinal changes in individuals with AD and FTLD. This model has also been validated against manual volumetric measurements for the automated regional segmentation of serial scans. Thus, it provides us with a useful tool in future research.