Alzheimer's disease (AD) is the most common type of dementia worldwide. Hippocampal atrophy and ventricular enlargement have been associated with AD but also with normal aging. We analyzed 1.5T brain MRI data from 46 cognitively normal elderly (NC), 33 mild cognitive impairment (MCI) and 43 AD subjects. Hippocampal and ventricular analyses were conducted with two novel semi-automated segmentation approaches followed by the radial distance mapping technique. Multiple linear regression was used to assess effects of age and diagnosis on hippocampal and ventricular volumes and radial distance. Additional 3D map correction for multiple comparisons was conducted with permutation testing. As expected, most significant hippocampal atrophy and ventricular enlargement were seen in the AD vs. NC comparison. MCI subjects showed intermediate levels of hippocampal atrophy and ventricular enlargement. Significant effects of age on hippocampal volume and radial distance were seen in the pooled sample as well as in the NC and AD groups considered separately. Age-associated differences were detected in all hippocampal subfields and the frontal and body/occipital horn portions of the lateral ventricles. Aging affects both the hippocampus and lateral ventricles independent of AD pathology and should be included as covariate in all structural hippocampal and ventricular analyses when possible.

Cerebrospinal fluid (CSF) measures of Ab and tau, Pittsburgh Compound B (PIB) imaging and hippocampal atrophy are promising Alzheimer’s disease biomarkers yet the associations between them are not known. We applied a validated, automated hippocampal labeling method and 3D radial distance mapping to the 1.5T structural magnetic resonance imaging (MRI) data of 388 ADNI subjects with baseline CSF Ab42, total tau (t-tau) and phosphorylated tau (p-tau181) and 98 subjects with positron emission tomography (PET) imaging using PIB. We used linear regression to investigate associations between hippocampal atrophy and average cortical, parietal and precuneal PIB standardized uptake value ratio (SUVR) and CSF Ab42, t-tau, p-tau181, t-tau/Ab42 and p-tau181/Ab42. All CSF measures showed significant associations with hippocampal volume and radial distance in the pooled sample. Strongest correlations were seen for p-tau181, followed by p-tau181/Ab42 ratio, t-tau/Ab42 ratio, t-tau and Ab42. p-tau181 showed stronger correlation in ApoE4 carriers, while t-tau showed stronger correlation in ApoE4 noncarriers. Of the 3 PIB measures the precuneal SUVR showed strongest associations with hippocampal atrophy.

We analyzed T1-weighted brain magnetic resonance imaging data of 100 cognitively normal elderly controls (NC), 127 cognitively normal PD (PDCN), 31 PD-associated mild cognitive impairment (PDMCI) subjects from the Norwegian ParkWest study. Using automated segmentation methods, followed by the radial distance technique and multiple linear regression we studied the effect of clinical diagnosis on hippocampal and ventricular radial distance while adjusting for age, education and scanning site. PDCN subjects had significantly smaller bilateral hippocampal radial distance relative to NC. Nonamnestic PDMCI subjects showed smaller right hippocampal radial distance relative to cognitively normal elderly. PDMCI subjects showed significant enlargement of all portions of the lateral ventricles relative to cognitively NC and significantly larger bilateral temporal and occipital and left frontal lateral ventricular expansion relative to PDCN subjects. Nonamnestic PDMCI subjects showed significant ventricular enlargement spanning all parts of the lateral ventricle while those with amnestic PDMCI showed changes localized to the left occipital horn. Hippocampal atrophy and lateral ventricular enlargement show promise as structural biomarkers for PD.

Background ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson’s disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement compared to normal controls. Here we aimed to investigate whether the same structural changes are associated with CSF levels of Aβ38, Aβ40, Aβ42, total tau and phosphorylated tau. Methods We performed 3D radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. Results We found significant associations between the levels of all three CSF Aβ analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample all three amyloid analytesshowed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aβ38 and Aβ42 showed negative associations with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. Conclusion CSF Aβ levels in early PD correlate with ventricular enlargement, previously associated with PDD. CSF and MRI markers may therefore help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer’s disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.