Low Subicular Volume as an Indicator of Dementia-Risk Susceptibility in Old Age.

Introduction: Hippocampal atrophy is an established Alzheimer's Disease (AD) biomarker. Volume loss in specific subregions as measurable with ultra-high field magnetic resonance imaging (MRI) may reflect earliest pathological alterations. Methods: Data from positron emission tomography (PET) for estimation of cortical amyloid ß (Aß) and high-resolution 7 Tesla T1 MRI for assessment of hippocampal subfield volumes were analyzed in 61 non-demented elderly individuals who were divided into risk-categories as defined by high levels of cortical Aß and low performance in standardized episodic memory tasks. Results: High cortical Aß and low episodic memory interactively predicted subicular volume [F(3,57) = 5.90, p = 0.018]. The combination of high cortical Aß and low episodic memory was associated with significantly lower subicular volumes, when compared to participants with high episodic memory (p = 0.004). Discussion: Our results suggest that low subicular volume is linked to established indicators of AD risk, such as increased cortical Aß and low episodic memory. Our data support subicular volume as a marker of dementia-risk susceptibility in old-aged non-demented persons.

Memory deficits for facial identity in patients with amnestic mild cognitive impairment (MCI).

Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.

Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.

Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59-82, 47.8% female), future converters at baseline (n = 10, age range 66-84, 90% female) and at time of conversion (age range 68-87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61-81, 47.8% female; n = 10, age range 66-82, 80% female; n = 10, age range 68-82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced hippocampal subfield volumes as potential markers for the early detection of Alzheimer's disease.

Hippocampal shape alterations are associated with regional Aß load in cognitively normal elderly individuals.

Aß deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aß deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging. We included 69 cognitively normal elderly subjects after careful clinical and neuropsychological workup. Standardized uptake value ratios (cerebellar reference) for uptake of 11-C-Pittsburgh Compound B (PiB) were calculated from positron emission tomographic data for a cortical measurement and for bilateral hippocampus, thalamus and striatum. Associations to shape, surface area, volume and cortical thickness were tested using regression models that included significant predictors as covariates. Left anterior hippocampal shape was associated with regional PiB uptake (P < 0.05, FDR corrected), whereas volumes of the hippocampi and their subregions were not associated with cortical or regional PiB uptake (all P > 0.05, FDR corrected). Within the entorhinal cortical region of both hemispheres, thickness was negatively associated with cortical PiB uptake (P < 0.05, FDR corrected). Hence, localized shape measures and cortical thickness may be potential biomarkers of presymptomatic Alzheimer's disease.

Microstructural Integrity of Hippocampal Subregions Is Impaired after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) affects a large number of individuals and diffusion tensor imaging can be used to investigate microstructural integrity of brain tissue after mTBI. However, results have varied considerably between studies and gray matter (GM) integrity has been largely neglected in these investigations. Given impaired working memory processing after mTBI and its possible association with Alzheimer's disease, we investigated hippocampal integrity and parcellated this structure into five subregions: subiculum, cornu ammonis (CA) 1, CA 2/3, CA 4/dentate gyrus, and stratum radiatum/lacunosum-moleculare. We also employed shape analysis of bilateral hippocampi to explore whether morphological changes had occurred due to the traumatic injury and conducted neuropsychological memory tests. The sample comprised 15 subjects with mTBI (18-55 years, nine female) and 13 age- and sex-matched healthy control subjects (19-57 years, nine female). Voxelwise analyses showed significantly increased mean diffusivity in patients, compared with controls, in the right hippocampus and three of its five subregions (family-wise error corrected p < 0.05). Additionally, results from probabilistic tractography indicated impaired CA 1 connectivity after mTBI (Benjamini-Hochberg false discovery rate [FDR] corrected p < 0.05). Shape of bilateral hippocampi did not significantly differ between groups (Benjamini-Hochberg FDR corrected p > 0.05). Subjects with mTBI reported more symptoms and performed worse in a non-standard verbal working memory task. Based on these preliminary findings, we were able to demonstrate altered diffusivity of hippocampal subregions following mTBI, indicating impaired GM microstructural integrity. These differences highlight the potential of diffusion imaging for investigation of subtle yet relevant changes in GM microstructure not detected otherwise following mTBI.

Volumetric and shape analysis of the thalamus and striatum in amnestic mild cognitive impairment.

Alterations in brain structures, including progressive neurodegeneration, are a hallmark in patients with Alzheimer's disease (AD). However, pathological mechanisms, such as the accumulation of amyloid and the proliferation of tau, are thought to begin years, even decades, before the initial clinical manifestations of AD. In this study, we compare the brain anatomy of amnestic mild cognitive impairment patients (aMCI, n = 16) to healthy subjects (CS, n = 22) using cortical thickness, subcortical volume, and shape analysis, which we believe to be complimentary to volumetric measures. We were able to replicate "classical" cortical thickness alterations in aMCI in the hippocampus, amygdala, putamen, insula, and inferior temporal regions. Additionally, aMCI showed significant thalamic and striatal shape differences. We observed higher global amyloid deposition in aMCI, a significant correlation between striatal displacement and global amyloid, and an inverse correlation between executive function and right-hemispheric thalamic displacement. In contrast, no volumetric differences were detected in thalamic, striatal, and hippocampal regions. Our results provide new evidence for early subcortical neuroanatomical changes in patients with aMCI, which are linked to cognitive abilities and amyloid deposition. Hence, shape analysis may aid in the identification of structural biomarkers for identifying individuals at highest risk of conversion to AD.