Elsevier

Neurobiology of Aging

Volume 22, Issue 2, March–April 2001, Pages 177-186
Neurobiology of Aging

Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly

https://doi.org/10.1016/S0197-4580(00)00238-4Get rights and content

Abstract

The sensitivity of MRI volumetric measures to detect cognitive dysfunction is examined in 39 participants of an epidemiological field study (age 75–85, MMSE 19–30). According to Clinical dementia rating (CDR), 17 subjects had normal cognition (CDR 0), 12 had questionable (CDR 0.5) and 10 mild dementia (CDR 1). Discriminant analysis based on four hippocampal measures resulted in a correct classification of 76.9% of all subjects. Left-sided and posterior hippocampal measures were more responsible for group discrimination than right-sided and anterior measures. In CDR 0.5, a significant hippocampal volume reduction of 14.3% vs.11.3% (left vs. right) relative to normal was found. The right hippocampus was significantly greater than the left in CDR 0 and CDR 0.5, but not in CDR 1. The magnitude of non-directional hippocampal asymmetry increased with decreasing cognitive state. We conclude that hippocampal atrophy is sensitive to detect cognitive dysfunction and subjects at risk for Alzheimer’s disease in the elderly population.

Introduction

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly.

The diagnosis of AD requires the presence of multiple cognitive deficits, including memory impairment, which are severe enough to interfere with activities of daily living [53]. The pathological processes underlying AD seem to be present years before the clinical diagnosis of AD can be made. Mild cognitive deficits are characteristic of the preclinical phase of AD. The transitional stage of mild cognitive impairment (MCI) in the elderly has become the subject of intensive investigation as a research category in the evaluation of preclinical Alzheimer’s disease [1], [42]. Subjects with MCI generally meet the criteria for “questionable dementia” when Clinical Dementia Rating (CDR) [22] is applied. “Questionable dementia” (CDR 0.5) refers to subjects with objective cognitive impairment who are not yet demented but have a high risk to develop dementia in the near future [46].

The hippocampal formation seems to be invariably involved in AD, which has led to the definition of AD as a hippocampal dementia [3]. Neurofibrillary tangles, i.e. histopathological changes typical of AD are found in large numbers in the hippocampus of demented patients with AD. The severity of neurofibrillary pathology in AD has been shown to correlate inversely with hippocampal volume measures in demented subjects [6], [40].

Previous neuroimaging studies have consistently shown that hippocampal atrophy (HA) is a sensitive marker for AD and that it provides high accuracy in discriminating normal controls and subjects with AD in more advanced stages [9], [23], [28], [36], [41].

A number of studies on subjects with memory impairment in the absence of dementia or on subjects with mild dementia showed that hippocampal atrophy is present very early in the course of AD [24], [26], [30], [34], [36], [41] and that it might even precede the onset of clinical symptoms [15], [25], [29]. However, most of these studies comprised only small numbers of subjects specifically selected to fulfill research criteria for distinct diagnostic groups. Hence, little can be said about the accuracy of hippocampal measures in the delineation of mild cognitive impairment and/or mild dementia in a non-selected population with a continuous range of cognitive functions.

The aim of this study is to examine whether measures of HA may be useful for the delineation of questionable dementia in a sample of subjects aged 75 to 85 which were consecutively recruited from an epidemiologic field study. In addition, the question as to which hippocampal measures are most sensitive for the detection of cognitive dysfunction in the elderly is addressed.

Section snippets

Subjects

We report on a subsample from the Leipzig Longitudinal Study of the Aged, LEILA 75+ [44], [45], a community-based study of 1692 randomly selected individuals aged 75 and older. The present sample includes the first 39 consecutively recruited subjects which will take part in an ongoing longitudinal neuroimaging study (LEILA-MCI).

As part of LEILA 75+, a fully structured interview was administered at a home visit during the time period January 1997 to June 1998. The core component of the interview

Results

Table 1 summarizes the demographic characteristics of the population. No group differences were present with regard to age and years of education. Statistically significant between-group differences were found in both left and right hippocampal volume estimates, the total brain volume and the total CSF volume. The volume estimates of both hippocampal bodies differed significantly over all three groups. The volumes of the right hippocampal head differed only between CDR 0.5 and 1, the volumes

Discussion

In this study involving a well characterized sample of elderly community-dwelling subjects with a continuous range of cognitive functions, we demonstrated that MRI volumetric measures of the hippocampus are sensitive in discriminating subjects with questionable dementia from subjects with normal cognition and mild dementia respectively.

Of the hippocampal parameters, the left hippocampus seemed to be more responsible for group discrimination than the right. Furthermore, measures of the more

Acknowledgements

This paper was supported by the Bundesministerium für Bildung und Technologie (BMB+F), Interdisziplinäres Zentrum für Klinische Forschung (IZKF) at the University of Leipzig (Projekt C8).

We wish to thank all participants of LEILA 75+ for their cooperation in this study.

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