The Role of Decreased Cortical Thickness and Volume of Medial Temporal Lobe Structures in Predicting Incident Psychosis in Patients With Alzheimer's Disease: A Prospective Longitudinal MRI Study.

OBJECTIVE: To investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based prospective longitudinal study enrolled 109 patients with AD. All patients with AD were evaluated at 3-month intervals to investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. OUTCOME MEASURE: The main outcome measure was time-to-progression from AD to incident psychosis. The thickness or volume of medial temporal lobe structures (i.e., the hippocampus, entorhinal cortex, and parahippocampus) were measured using magnetic resonance imaging and the Freesurfer automated segmentation pipeline at baseline. RESULTS: Multivariate Cox proportional hazards regression analysis revealed that a decreased cortical thickness or volume of medial temporal region was associated with a higher risk of incident psychosis in patients with AD. The hazard ratios for decreased cortical thickness of the left entorhinal cortex and decreased cortical volume of the right hippocampus were 4.291 (95% confidence interval [CI], 1.196-15.384) and 2.680 [(CI, 1.003-1.196]), respectively. CONCLUSION: Our study revealed that decreased cortical thickness or volume of medial temporal sub-regions is a risk factor for incident psychosis in patients with AD. A careful assessment of the thickness or volume of the medial temporal lobe structures in AD may improve early detection and intervention of psychosis in AD.

The Relationship of Plasma Transthyretin Level with Global or Regional Amyloid Beta Burden in Subjects with Amnestic Mild Cognitive Impairment: Cross-Sectional Amyloid PET Study.

Background: To investigate the relationships of plasma transthyretin levels with amyloid beta deposition and medial temporal atrophy in amnestic mild cognitive impairment. Methods: This is a cross-sectional study of association of subjects with amnestic mild cognitive impairment. Plasma transthyretin levels, brain magnetic resonance imaging, and 18F-florbetaben positron emission tomography were simultaneously measured in subjects with amnestic mild cognitive impairment. Results: Plasma transthyretin levels were positively associated with amyloid beta deposition in global (r = 0.394, P = .009), frontal cortex (r = 0.316, P = .039), parietal cortex (r = 0.346, P = .023), temporal cortex (r = 0.372, P = .014), occipital cortex (r = 0.310, P = .043), right posterior cingulate (r = 0.350, P = .021), left precuneus (r = 0.314, P = .040), and right precuneus (r = 0.398, P = .008). No association between plasma transthyretin level and medial temporal sub-regional atrophies was found. Conclusions: Our findings of positive association of plasma transthyretin levels with global and regional amyloid beta burden suggest upregulation of transthyretin level as a reactive response to amyloid beta deposition during the early stages of the Alzheimer's disease process.

Association of Temporolimbic Volumes with Treatment Response to Antipsychotic Medication for Delusion in Patients with Alzheimer's Disease.

Objective: This study investigated the association between gray matter volume and the treatment response to antipsychotic medication in patients with Alzheimer's disease (AD). Methods: We included 26 AD patients with delusions from the Memory Impairment Center of the Pusan National University Hospital in South Korea. All participants underwent baseline brain magnetic resonance imaging and took risperidone as an antipsychotic medication for 6 weeks. Gray matter volumes were measured using voxel-based morphometry at baseline. Treatment response with respect to delusional symptoms was defined as the change in delusion item scores in the Korean version of the Neuropsychiatry Inventory (K-NPI), from baseline to 6 weeks later. A voxel-based multiple linear regression model integrated with statistical parametric mapping was used to investigate the association between gray matter volume and treatment response after controlling for covariates. Results: The treatment response was significantly positively correlated with gray matter volume in the temporal lobe (both the fusiform gyri and the left superior and inferior temporal gyri) and the limbic system (the left parahippocampal gyrus and left amygdala) after controlling for age, sex, education level, total intracranial volume, risperidone dosage, baseline Korean version of the Mini-Mental Status Examination scores, and baseline K-NPI scores for the delusion and non-delusion domains (P < .001, uncorrected, KE > 100 voxels). Conclusion: Our findings suggest that specific gray matter volumes, including those of the temporal region and the limbic system, may affect treatment response to antipsychotic medication in terms of delusional symptoms in patients with AD.