Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease

Abstract

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...

The relation between global and limbic brain volumes on MRI and cognitive performance in healthy individuals across the age range

“…Volumes of hippocampus and parahippocampal gyrus were found to decline significantly with age. Several authors have reported similar age-related volume decreases in these regions [8,9,12,18,26,31]. However, other authors have failed to find such a decline in medial temporal lobe volumes [24,31,37].…”

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

“…In addition, subjects in this treatment trial were drawn from the recruitment base for the ADCS -dementia and memory disorders referral centers. Conversely, the majority of subjects in Mayo Clinic MRI studies are drawn from a community sample (Petersen et al, 1990;Jack et al, 1997).…”

“…Four different brain atrophy brain measures were assessed; the hippocampus, entorhinal cortex (ERC), whole brain, and ventricular volume. Each of these MRI measurements has figured prominently in anatomic MRI based studies of MCI, AD, and normal aging (Jack et al, 1992;Fox et al, 1996;Jack et al, 1997;Fox et al, 1999;Killiany 2000;Dickerson et al, 2001;Killiany et al, 2002;Du et al, 2003). A primary objective of this analysis was to test the hypothesis that vitamin E or donepezil slowed the rate of brain atrophy relative to placebo in subjects with amnestic MCI (Petersen 1995;Petersen et al, 1999).…”

“…In addition, subjects in this treatment trial were drawn from the recruitment base for the ADCS -dementia and memory disorders referral centers. Conversely, the majority of subjects in Mayo Clinic MRI studies are drawn from a community sample (Petersen et al, 1990;Jack et al, 1997).A second objective of this study was to assess correlations between the rates of change on MRI and concurrent change on standard instruments employed in clinical trials; MMSE, CDR, and ADAS-Cog 11 and 13 item scales (Table 3 and Figure 3). Change in MRI mapped onto concurrent change in test performance in a uniformly significant and biologically sensible manner.…”

Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

“…In vivo magnetic resonance (MR) imaging studies have reported substantial volume loss in the hippocampus in subjects with very mild or mild dementia of the Alzheimer type (DAT) (Dickerson et al, 2001;Du et al, 2001;Fox et al, 1996;Jack et al, 1997;Killiany et al, 2002). However, structural deformation of the substructures of the hippocampus in early DAT has not been adequately examined.…”