Brain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2

BackgroundIn preclinical Alzheimer's disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions.MethodsWe tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol.ResultsIn asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Ass42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs.ConclusionsThese data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline

Sporadic Creutzfeldt-Jacob Disease: Analysis of 16 Patients

Objectives:Creutzfeldt-Jacob Disease (CJD) is a rare neurodegenerative disorder. This study is a review of clinical findings and diagnostic procedures used for 16 patients diagnosed with sporadic CJD (sCJD) at Ankara University School of Medicine.Methods:Medical records of 16 patients who were diagnosed with sCJD between January 1990 and January 2015 were analyzed. Clinical features, periodic sharp and slow wave complexes (PSSW) in electroencephalography (EEG), finding of 14-3-3 protein in cerebrospinal fluid (CSF) and brain magnetic resonance imaging (MRI) of all patients were assessed.Results:Study included 16 patients with sCJD: 6 females (37.5%) and 10 males (62.5%), with mean age 64±9.5 years. All patients had dementia and myoclonus; 14 patients had extrapyramidal or pyramidal signs, 13 had cerebellar (n=10) and/or visual signs (n=6), and 10 patients had akinetic mutism. PSSW were present in EEG of 13 patients. Brain MRI of 13 patients showed abnormalities and 14-3-3 protein was detected in CSF of 6 of 7 patients. Within an average period of 3 months from the onset of signs, 9 hospitalized patients died.Conclusion:It is important to consider diagnosis of sCJD in patients with rapidly progressive dementia