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IC‐P‐099: Elevated PiB precedes dementia in autosomal dominant Alzheimer's disease: PiB, FDG and atrophy in the DIAN cohort
Author(s) -
Benzinger Tammie,
Blazey Tyler,
Koeppe Robert,
Jack Clifford,
Raichle Marcus,
Su Yi,
Snyder Abraham,
Marcus Daniel,
Ringman John,
Thompson Paul,
Ghetti Bernardino,
Saykin Andrew,
Salloway Stephen,
Correia Steve,
Johnson Keith,
Sperling Reisa,
Schofield Peter,
Masters Colin,
Rowe Christopher,
Villemagne Victor,
Rowe Christopher,
Fox Nick,
Brickman Adam,
Mayeux Richard,
Martins Ralph,
Mathis Chester,
Klunk William,
Weiner Michael,
Bateman Randall,
Fagan Anne,
Goate Alison,
Cairns Nigel,
Buckles Virginia,
Moulder Krista,
Morris John
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.132
Subject(s) - dementia , putamen , cohort , medicine , clinical dementia rating , population , atrophy , pittsburgh compound b , grey matter , pathology , psychology , white matter , nuclear medicine , oncology , disease , magnetic resonance imaging , radiology , environmental health
notype on psychometric performance, amyloid deposition and neurodegeneration in patients with very mild clinical impairments. Methods: Baseline pre-processed AV-45 PET scans [2], 3T MRI scans [3], APOE genotype [4] and other quantitative phenotypes were downloaded from the ADNI website. Only participants categorized as EMCI (n 1⁄4 139) at baseline from ADNI-GO/2 were included. MRI scans were processed using VBM, as previously described [5]. AV-45 scans were co-registered to the concurrent MRI and normalized to MNI space using parameters generated from MRI segmentation. Differences between APOE E4 allele positive and negative participants in AV-45 standardized uptake on a voxel-wise basis were assessed using a twosample t-test using SPM8. Region of interest (ROI) data was extracted from MRI and AV-45 scans using MarsBaR. Neuropsychological performance, cognitive complaints, and ROI data were compared between E4 positive and negative participants using independent-samples t-tests (SPSS 19.0). Results: Approximately 42% of the E-MCI participants (n 1⁄4 139) were APOE E4 positive (n 1⁄4 59; 2 E2E4, 48 E3E4, 9 E4E4; Table 1). The E4 positive E-MCI group showed lower performance on memory and global cognitive measures, but a trend toward fewer cognitive complaints, than APOE E4 negative participants (n 1⁄4 80; 9 E2E3, 71 E3E3). On AV-45 PET, E4 was associated with increased amyloid deposition, particularly in frontal and medial parietal lobar regions (Figure 1A; P <0.05 FWE, k 1⁄4 50). Similarly, ROI analyses indicated greater amyloid deposition in the frontal lobes of E4 positive E-MCI participants (Figure 1B; P <0.001). By contrast, the presence of E4 was not associated with greater hippocampal atrophy in this initial sample of E-MCI participants (Figure 1C). Conclusions: In E-MCI, APOE E4 genotypes are associated with greater amyloid deposition and cognitive changes, but not hippocampal neurodegeneration. References: [1] Corder (1993). [2] Jagust (2010). [3] Jack (2010). [4] Saykin (2010). [5] Risacher (2009).