WM tract degeneration is prominent in SCI and MCI patients, and is at least in part independent of overlying gray matter atrophy.

Neuropathological correlates of Alzheimer's disease (AD) emerge years before dementia. Biomarkers preceding cognitive decline and reflecting the causative processes can potentially aid early intervention and diagnosis. Diffusion tensor imaging (DTI) indirectly reflects tissue microstructure. To answer whether DTI is an early biomarker for AD and to explore the relationship between DTI and the established biomarkers of medial temporal lobe atrophy and cerebrospinal fluid (CSF) Aβ(42), T-tau, and P-tau, we longitudinally studied normal controls and patients with subjective (SCI) or mild (MCI) cognitive impairment. 21 controls and 64 SCI or MCI cases recruited from a university-hospital based memory clinic were re-examined after two to three years. FreeSurfer was used for longitudinal processing of morphometric data, and DTI derived fractional anisotropy, radial diffusivity, and mean diffusivity were analyzed in Tract-Based Spatial Statistics. Using regression models, we explored and compared the predictive powers of DTI and CSF biomarkers in regard to cognitive change and atrophy of the medial temporal lobe. Both DTI and CSF biomarkers significantly predicted cognitive decline and atrophy in the medial temporal lobe. In this population, however, DTI was a better predictor of dementia and AD-specific medial temporal lobe atrophy than the CSF biomarkers. The case for DTI as an early biomarker for AD is strengthened, but further studies are needed to confirm these results.

No abstract

Abstract. While APOE ε4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of A␤ 42 (pA␤) and APOE ε4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or * Correspondence to: Lene Pålhaugen, P.B. 1000, N-1478 Lørenskog, Norway. Tel.: +47 95832775; E-mail: lene. palhaugen@gmail.com. 98 T. Fladby et al. / Detecting At-Risk AD Casesmild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pA␤ and APOE ε4 frequency compared to NC. Also, NCFD had higher APOE ε4 frequencies without increased fraction of pA␤ compared to NC, and cases recruited from memory clinics had higher fractions of pA␤ and APOE ε4 frequency than self-referred. This study shows that memory clinic referrals are pA␤ enriched, whereas self-referred and NCFD cases more frequently are pA␤ negative but at risk (APOE ε4 positive), suitable for primary intervention.