Measurements of medial temporal lobe atrophy for prediction of Alzheimer's disease in subjects with mild cognitive impairment

Abstract

Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n = 156) and the single-center VU medical center (n = 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1-42. MTA-score and lateral ventricle volume correlated with CSF beta-amyloid 1-42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI.

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer’s Disease

“…Our team of multi-disciplinary clinicians (HIJ, JK,öO, NR, BR) meticulously ensured the compliance of these criteria for every included SCD participants prior to classifying them as such. Prodromal AD patients had to fulfill the latest research criteria proposed by Albert et al [36], Dubois et al [37,38], and Petersen [39]: self-reported memory complaints or informed by a knowledgeable caregiver (verified during the anamnesis or using the cut-off value of ≥25 on the MAC-Q) [32] along with objective cognitive deficits (corrected for age, gender, and education) of at least 1.5 SD from the normative mean [39,40], a mini mental status examination score of ≥23 [41], and, most important, evidence of biomarkers, i.e., cerebrospinal fluid tau/A␤ 42 ratio of >0.52 [42], medial temporal lobe atrophy score ≥3 using MR imaging [43], or typical temporoparietal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG-PET) imaging [36,44], but preserved activities of daily living (confirmed by a clinician during the anamnesis or by the Bayer Activities of Daily Living Scale cut-off of >5) [45]. This combination of evidence ensures the selection of patients that have the highest probability of converting to AD and are thus considered prodromal AD patients [37,38].…”

AlzheimerÂ’s and ParkinsonÂ’s Diseases Face Common Challenges in Therapeutic Development: Role of the Precompetitive Consortium, Coalition Against Major Diseases

“…Analysis of three different datasets produced encouraging results [13][14][15], suggesting that the variability of cutpoints among different studies is low; however, it has been difficult to obtain data from published analyses that could be reanalyzed to confirm this finding.…”

Cognitive correlates of cerebrospinal fluid biomarkers for Alzheimer’s disease

“…As emerging risk factors we will test social inactivity [27], cognitive and physical inactivity [28][29][30], alcohol consumption [31], smoking [28,29] and sleep deprivation [28,29,32,33].…”

“…The Paired Associates Learning (PAL) of the computerized CANTAB [30,31], is a visuospatial episodic memory task in which individuals were asked to pair a token with its location as follows. One or more white boxes revealed a unique token.…”

“…Task difficulty gradually increased from two to eight tokens and box locations. Outcome measure was the total number of errors made across all difficulty stages adjusted for the stages not attempted due to previous failure, which has been found a promising marker for early AD [30,32] In the Spatial Working Memory (SWM) task of the CANTAB [33,34] individuals had to search for one blue token in a number of boxes. The token appeared in a new location each time and the individual was asked not to return to a box where a token has already been found.…”