Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly
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.
References (55)
- et al.
A new definition of Alzheimer’s diseasea hippocampal dementia
Lancet
(1985) - et al.
Neurofibrillary pathology—correlation with hippocampal formation atrophy in Alzheimer disease
Neurobiol Aging
(1996) - et al.
Progression to dementia in patients with isolated memory loss
Lancet
(1997) - et al.
Hippocampal volume losses in minimally impaired elderly
Lancet
(1995) - et al.
Specific hippocampal volume reductions in individuals at risk for Alzheimer’s disease
Neurobiol Aging
(1997) - et al.
Abnormalities of regional brain metabolism in Alzheimer’s disease and their relation to functional impairment
Prog Neuropsychopharmacol Biol Psychiatry
(1986) - et al.
Volumes of medial temporal lobe structures in patients with Alzheimer’s disease and mild cognitive impairment (and in healthy controls)
Biol Psychiatry
(1998) - et al.
MRI of the hippocampus in Alzheimer’s diseasesensitivity, specificity, and analysis of the incorrectly classified subjects
Neurobiol Aging
(1998) - et al.
Mild cognitive impairment—an early stage of Alzheimer’s disease?
J Neural Transm Suppl
(1998) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study
Acta Neuropathol (Berl)
(1977)
Age-associated memory impairmentdiagnostic and treatment issues
Int J Geriat Psychiatry
Volumetric MRI of the limbic systemanatomic determinants
Neuroradiology
Hippocampal atrophy in early Alzheimer’s diseaseanatomic specificity and validation
Psychiatr Q
Hippocampal sclerosis contributes to dementia in the elderly
Neurology
The radiologic prediction of Alzheimer diseasethe atrophic hippocampal formation
AJNR Am J Neuroradiol
Questionable dementiaclinical course and predictors of outcome
J Am Geriatr Soc
Presymptomatic hippocampal atrophy in Alzheimer’s disease. A longitudinal MRI study
Brain
Examination of the validity of the hierarchical model of neuropathological staging in normal aging and Alzheimer’s disease
Acta Neuropathol (Berl)
Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human developmentages 4–18 years
J Comp Neurol
Segmentation of white matter lesions from volumetric MR-images
Hippocampal volume measurements using magnetic resonance imaging in normal young adults
J Neuroimaging
Magnetic resonance imaging volumetric measurements of the superior temporal gyrus, hippocampus, parahippocampal gyrus, frontal and temporal lobes in late paraphrenia
Psychol Med
A new clinical scale for the staging of dementia
Br J Psychiatry
MRI-based quantitative assessment of the hippocampal region in very mild to moderate Alzheimer’s disease
Neuroradiology
MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease
Neurology
Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment
Neurology
Cited by (144)
The unique effect of TDP-43 on hippocampal subfield morphometry and cognition
2022, NeuroImage: ClinicalCitation Excerpt :The hippocampus, and specifically its subfields, has been associated with unique functions both across the cytoarchitecturally distinct segments, and functional distinction along the long-axis, indicating specialization for anterior/posterior segmentations, due to their unique anatomical connections (de Wael et al., 2018). While most biomarker research surrounds hippocampal volumetry, hippocampal shape has been shown to be more sensitive in predicting disease progression in particular subfields in patients with dementia of the Alzheimer’s type (DAT) as compared to controls (Csernansky et al., 2005; Wang et al., 2003) and studied in a variety of clinical groups (Cabinio et al., 2018; La Joie et al., 2013; Li et al., 2016; Wolf et al., 2001). While research has explored the relationship of hippocampal subfields to cognition, the literature is inconsistent (Xu et al. 2020; de Flores et al., 2015).
Chronic Kidney Disease and Cognitive Impairment
2021, Journal of Stroke and Cerebrovascular DiseasesAsymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid-positive mild cognitive impairment is associated with key clinical features
2019, Alzheimer's and Dementia: Diagnosis, Assessment and Disease MonitoringCitation Excerpt :With regard to functional mobility, only the left-lateralized damage of the VM and VPL subnuclei were related to the Bristol Activities of Daily Living score. The normal asymmetric structure and function of the human brain has evolutionary and developmental origins [34] but can also be indicative of neurological disorders [7,34]. We examined the degree of thalamic asymmetry in AD, spanning amyloid-positive MCI and dementia.
A review of neuroimaging-based data-driven approach for Alzheimer’s disease heterogeneity analysis
2024, Reviews in the Neurosciences