Impaired Frontolimbic Connectivity and Depressive Symptoms in Patients with Alzheimer's Disease.

BACKGROUND/AIMS: Depressive symptoms are commonly observed in Alzheimer's disease (AD). The underlying mechanisms of depressive symptoms in AD remain unclear; frontolimbic circuitry dysfunction may play a role. We aimed to investigate the microstructural integrity of frontolimbic connectivity of specific fiber tracts in AD patients with and without depressive symptoms using diffusion tensor imaging (DTI). METHODS: Eleven AD patients with depressive symptoms (dep-AD), 18 AD patients without depressive symptoms (nondep-AD), and 18 normal control (NC) subjects were included. The cingulum bundle (CB), uncinate fasciculus (UF), and fornix, mainly frontolimbic connectivity, were measured by DTI tractography and the metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were calculated. RESULTS: Compared with NC subjects, both dep-AD and nondep-AD patients showed significant differences for all indices in the fornix and significantly decreased FA and increased MD and RD in the bilateral CB and UF. When compared to nondep-AD patients, dep-AD patients showed significantly increased MD and RD in the bilateral CB and right UF. CONCLUSION: Depressive symptoms in AD patients may be involved in greater microstructural abnormalities of frontolimbic connectivity and myelin injury in the bilateral CB and right UF might contribute to the pathophysiology of depressive symptoms in AD.

Disruption of thalamic connectivity in Alzheimer's disease: a diffusion tensor imaging study.

The aim of this study was to evaluate the structural integrity of the thalamic connectivity of specific fiber tracts in different stages of Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Thirty-five patients with AD and 22 normal control (NC) subjects were recruited. Based on Mini Mental State Examination score, the AD patients were divided into three subgroups for comparison with the NC group: mild (mi-AD, n = 14), moderate (mo-AD, n = 12), and severe (se-AD, n = 9) AD. The fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR) were selected to represent the thalamic connectivity with other brain regions. The fornix was divided into the column and body of the fornix (FX-1) and the bilateral fornix (crus)/stria terminalis (FX-2/ST) based on the atlas. Through the atlas-based analysis and fiber tracking method, we measured fractional anisotropy (FA), mean diffusivity (MD), and tract volume to reflect the microstructural and macrostructural changes of these fibers during AD progression. There were significant differences in the FA and MD of all fibers, except the right PTR, between the AD and NC subjects. Further subgroup analyses revealed that the mi-AD subgroup had decreased FA only in the FX-1 and increased MD in the FX-1 and bilateral ATR, the mo-AD subgroup showed declined FA and increased MD in the FX-1, bilateral FX-2/ST and ATR; the se-AD subgroup exhibited lower FA and higher MD values in all fibers except the right PTR. We also found reduced tract volume values in the FX and left ATR in the AD patients. Further subgroup analyses revealed that these differences only existed in the se-AD patients. Our DTI analyses indicate that the integrity of thalamic connectivity is progressively disrupted following cognitive decline in AD and that DTI parameters in the column and body of the fornix show promise as potential markers for the early diagnosis of AD and for monitoring disease progression.