Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.

Objective-To test the hypothesis that magnetic resonance imaging (MRI)-based measurements of hippocampal volume were related to the risk of future conversion to Alzheimer's disease (AD) in elderly patients with a mild cognitive impairment (MCI) Background-Persons who develop AD pass through a transitional state which can be characterized as a MCI. However, in some patients MCI is a more benign condition which may not progress to AD or may do so slowly.

Magnetic resonance imaging(MRI) based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly controls and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly controls and AD patients with the very mildest form of the disease. We performed MRI-based volume measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly controls and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR = 0.5 were classified as very mild, CDR = 1 as mild, and CDR = 2 moderate disease severity.Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (P<.001). Of the several MTL measures, the total hippocampal volume measurements were best at discriminating controls from AD cases. The mean hippocampal volumes for AD patients relative to controls by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age and gender adjusted normalized MRI-based hippocampal volume measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process. KeywordsAlzheimer's Disease; Dementia; MRI; Quantitative MRI; Hippocampus Alzheimer's disease(AD) is the most common cause of dementia in individuals over 60 years of age(1-3). A well accepted biological concomitant of AD is cerebral atrophy(4). The rationale for quantitative magnetic resonance imaging (MRI) of medial temporal lobe (MTL) atrophy in the diagnosis of AD is: 1) A memory impairment is usually the earliest and most severe clinical manifestation of AD; 2) Medial temporal lobe (MTL) limbic structures are central to the integrity of declarative memory function (5); 3) MTL limbic structures are involved earliest and most extensively in the pathology of AD(6,7); and 4) several principal MTL limbic structures are amenable to accurate volumetric quantitation by MRI-the hippocampal 3) Relatively small numbers of subjects were included in individual studies. 4) Rigorous definitions of the severity of AD often were not employed. Most previous studies have included primarily subjects with AD of moderate severity. Consequently, the differences between the AD patients and control subjects with regard to MTL atrophy have been dramatic. The most important test of the utility of the technique would be in patients with very mild AD in whom the diagnostic decision making process is difficult.We report a large series of carefully evaluated and lon...

MRI-based hippocampal volumetry accurately depicts the structural-functional relationships between memory loss and hippocampal damage across the spectrum from normal aging to dementia.

Background: It was recently demonstrated that the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) score can be used to accurately stage severity of Alzheimer dementia and mild cognitive impairment (MCI). However, to our knowledge, the utility of those interpretive guidelines has not been cross-validated or applied to a heterogeneous sample of dementia cases.Objective: To cross-validate the staging guidelines proposed in a previous study using the National Alzheimer's Coordinating Center (NACC) database. Design:The previously published cut scores were applied to the NACC sample and diagnostic accuracy estimates obtained. Next, analyses were restricted to NACC participants with a CDR global score (CDR-GS) of 0.5 and receiver operating characteristic curves generated to determine optimal CDR-SB cut scores for distinguishing MCI from very early dementia. Setting:The 2008 NACC uniform data set.Participants: There were 12 462 participants (5115 controls; 2551 patients with MCI; 4796 patients with de-mentia, all etiologies) in the NACC data set used for the current analysis.Main Outcome Measure: Accurate prediction of diagnoses (MCI or dementia) using the CDR-SB score. Results:The previously proposed CDR-SB ranges successfully classified the vast majority of patients across all impairment ranges with a of 0.91 and 94% overall correct classification rate. Additionally, the CDR-SB score discriminated between patients diagnosed with MCI and dementia when CDR-GS was restricted to 0.5 (overall area under the curve=0.83).Conclusions: These findings cross-validate the previously published CDR-SB interpretative guidelines for staging dementia severity and extend those findings to a large heterogeneous sample of patients with dementia. Additionally, the CDR-SB scores distinguished MCI from dementia in patients with reasonable accuracy when CDR-GS was restricted to 0.5.