Diagnosis of Alzheimer’s disease: MRI of the hippocampus vs delayed recall
Introduction
The pathology of Alzheimer’s disease (AD) affects most areas of the brain. The implications of this are also reflected in the neuropsychology of AD, where alterations can be found in practically all domains, such as long or short term memory, working memory, implicit, explicit, semantic or episodic memory [24]. Even commonly used diagnostic criteria of AD do not refer to changes in specific cognitive domains as sensitive or specific indicators of AD. For instance, the NINCDS-ADRDA [30] or the DSM-IV [3] criteria merely state that there should be decline in several areas of cognition in AD, out of which at least two are required for a diagnosis of dementia. It could be argued, however, that not all of the multiple cognitive domains are of equal importance from a diagnostic point of view. Indeed, the diagnostic tests for AD have increasingly focused around the medial temporal lobe (MTL) memory system, i.e. the hippocampus and the adjacent cortical areas. In the initial stages of AD, neuropathological changes, in particular neurofibrillary tangles (NFT), are first observed to appear in the MTL, and at the end-stage of the disease these regions are also the ones most severely affected [5], [8], [19], [20]. The NFTs also display the most characteristic, hierarchical distribution pattern in the MTL [23], [34], and show substantial correlation with the clinical severity in AD [4], [6], [7]. Selective lesions of the MTL memory system are known to produce deficits in memory storage while preserving immediate and remote recall as well as general intelligence [38]. In other words, encoding or storage of recently acquired data fails, which is reflected as an inability to retrieve the data in tests assessing delayed recall. Therefore, distribution of AD pathology could be used as a hypothesis or an argument why poor performance in tests assessing delayed recall could be considered as rather sensitive finding in early AD.
Indeed, impaired performance in tests assessing delayed recall has been found to be an early feature of dementia, but to remain essentially intact during cognitively normal aging [17], [31], [32], [33], [40]. This is in agreement with findings from volumetric magnetic resonance imaging (MRI) studies which to date have provided clear evidence that hippocampal atrophy is a valuable method to support the clinical diagnosis of early AD [14], [22], [27], [28], [37]. Similarly, the largest of these studies have indicated that there is no [28] or only minor [22] hippocampal volume loss in cognitively normal aging. Furthermore, several MRI studies have shown that the volumes of the hippocampus and adjacent cortical structures correlate with the delayed recall performance in AD and to some extent in normal aging although the case for the latter is rather equivocal [9], [10], [16], [26], [27], [29], [37]. Therefore, it is plausible that neuroanatomical and neuropsychological approaches reflect two sides of the very same phenomenon, i.e., the disintegration of the MTL memory system.
However, the question of the comparative diagnostic utility of these two approaches has not been addressed. To answer this question, we compared the accuracy of hippocampal volumetry and widely used test of delayed recall, Russel’s Adaptation of the Visual Reproduction Test (VRT) [36], to discriminate patients with early probable AD from cognitively normal control subjects.
Section snippets
Subjects
A total of 91 subjects were examined in the study. Subjects included 57 patients fulfilling the NINCDS-ADRDA criteria of probable AD [30], and 34 cognitively normal age- and gender-matched controls. The study was approved by the local ethics committee. Following explanation of the study protocol, all subjects provided their informed consent for participation in the study. The demographics of the study groups are listed in Table 1.
The AD patients chosen for the study were recruited from
Results
Neither the gender distribution (χ20.3, d.f. 1, P=0.60) nor age (F=1.1, P=0.38) differed between the groups. By definition, the AD patients scored worse on the MMSE (F=81.4, P<0.0001), as well as on the VRT performance (F=275.5, P<0.0001).
In the control subjects, correlations between the hippocampal volumes and the MMSE or the VRT scores never approached significance. In the AD patients, the hippocampal volumes correlated significantly with the MMSE scores on the left (r=0.52, P<0.0001), and
Discussion
In this study we have confirmed previous findings that the volumetric hippocampal atrophy [22], [28] and tests assessing delayed recall [40] are valuable aids in the diagnosis of early probable AD, as well as those suggesting correlations between the hippocampal volumes and delayed recall performance [9], [10], [16], [26], [27], [29], [37]. The novel finding in this study relates to the comparative accuracy of hippocampal volumetry and delayed recall performance as diagnostic tests of early
Acknowledgements
The study was supported by the Research Council for Health of the Academy of Finland, and an EVO grant from the Kuopio University Hospital.
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