Cathleen Haense

Evaluation of a Calibrated 18F-FDG PET Score as a Biomarker for Progression in Alzheimer Disease and Mild Cognitive Impairment

Increasingly, clinical trials are being planned in patients with mild cognitive impairment (MCI) to prevent or delay the onset of dementia in Alzheimer disease (AD) by disease-modifying intervention. Inclusion of imaging techniques as biomarkers for patient selection and assessment of outcome is expected to increase trial efficacy. PET using 18F-FDG provides objective information about the impairment of synaptic function and could, with appropriate standardization, qualify as a biomarker. Methods: We evaluated a predefined quantitative measure (PET score) that is extracted automatically from 18F-FDG PET scans using a sample of controls (n = 44), patients with MCI (n = 94), and patients with mild AD (n = 40) from the Alzheimer Disease Neuroimaging Initiative (ADNI). Subjects received 4 scans and clinical assessments over 2 y. Results: PET scores provide much higher test–retest reliability than standard neuropsychologic test scores (Alzheimers Disease Assessment Scale–Cognitive [ADAS-cog] and Mini-Mental State Examination) and superior signal strength for measuring progression. At the same time, they are related linearly to ADAS-cog scores, thus providing a valid measure of cognitive impairment. In addition, PET scores at study entry in MCI patients significantly predict clinical progression to dementia with a higher accuracy than Mini-Mental State Examination and ADAS-cog. Conclusion: 18F-FDG PET scores are a valid imaging biomarker to monitor the progression of MCI to AD. Their superior test–retest reliability and signal strength will allow the reduction in the number of subjects needed or shortening of study duration substantially.

Cholinergic system function and cognition in mild cognitive impairment

Evidence for cholinergic dysfunction in very early stages of neurodegeneration like mild cognitive impairment (MCI) is inconclusive. Previous positron emission tomography (PET) studies based on small samples investigated if it is related to memory impairment. We examined whether cortical acetylcholine esterase (AChE) activity is reduced at this stage and correlated with cognitive function. N-[(11)C]-methyl-4-piperidyl acetate ([11C]MP4A), a positron emission tomography tracer for measuring cerebral AChE activity in vivo, was applied in 21 controls and 17 MCI patients. Parametric images of AChE activity were analyzed using standard atlas regions. Principal components analysis (PCA) of regional values of AChE activity and correlation analysis with neuropsychological test results was performed. Cortical AChE activity showed a significant decline in MCI patients compared with controls which was most pronounced in temporal regions. They formed the main part of a principal component that was related significantly to verbal and nonverbal memory, language comprehension and executive function. Cholinergic dysfunction is an early hallmark even before onset of dementia at the clinical stage of MCI. Its impact especially on temporal neocortex is associated with impaired neuropsychological function.

Early signs of VCP-related frontotemporal dementia: a neuropsychological, FDG-PET and fMRI study

Kalbe, Elke Onur, Oezguer A Minnerop, Martina Reimann, Jens Althaus, Astrid Ahmadzadehfar, Hojjat Dodel, Richard Strach, Katharina Clemen, Christoph S Herholz, Karl Haense, Cathleen Fink, Gereon R Schroder, Rolf Letter Research Support, Non-U.S. Govt Germany Journal of neurology J Neurol. 2011 Mar;258(3):515-8. Epub 2010 Oct 12.

Metabolic regional and network changes in Alzheimer's disease subtypes

Clinical variants of Alzheimers disease (AD) include the common amnestic subtype as well as subtypes characterised by leading visual processing impairments or by multimodal neurocognitive deficits. We investigated regional metabolic patterns and networks between AD subtypes. The study comprised 9 age-matched controls and 25 patients with mild to moderate AD. Methods included clinical and neuropsychological assessment, high-resolution FDG PET and T1-weighted 3D MR imaging with PET-MR coregistration, grey matter segmentation, atlas-based regions-of-interest, linear mixed effects and regional correlation analysis. Regional metabolic patterns differed significantly between groups, but significant hypometabolism in the posterior cingulate cortex (PCC) was common to all subtypes. The most distinctive regional abnormality was occipital hypometabolism in the visual subtype. In controls, two large clusters of positive regional metabolic correlations were observed. The most pronounced breakdown of the normal correlation pattern was found in amnestic patients who, in contrast, showed the least regional focal metabolic deficits. The normal positive correlation between PCC and hippocampus was lost in all subtypes. In conclusion, PCC hypometabolism and metabolic correlation breakdown between PCC and hippocampus are the common functional core of all AD subtypes. Network alterations exceed focal regional impairment and are most prominent in the amnestic subtype.

Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease

To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early‐onset Alzheimers disease.