Diffusion tensor changes in patients with amnesic mild cognitive impairment and various dementias

https://doi.org/10.1016/j.pscychresns.2008.09.002Get rights and content

Abstract

White matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. To explore white matter changes in different types of dementia, we examined brain water diffusivity with diffusion tensor imaging (DTI). We measured fractional anisotropy and mean diffusivity of multiple white matter regions in patients with amnesic mild cognitive impairment (MCI, n = 10), Alzheimer's disease (AD, n = 30), subcortical ischemic vascular dementia (SIVD, n = 18), frontotemporal dementia (FTD, n = 7), and control subjects (n = 20). We performed pairwise comparisons in each region of interest between patients and controls. MCI patients showed diffusion tensor change (DTC) in the left anterior periventricular (PV) area, possibly in the right posterior PV area, and the genu of the corpus callosum. AD patients showed DTC in the corpus callosum, and in frontal and parieto-occipital subcortical and anterior PV areas. In SIVD patients, DTC occurred in the genu of the corpus callosum, and in bilateral frontal subcortical and PV areas. FTD patients differed from controls in showing DTC in the temporal and frontal subcortical areas, the genu of the corpus callosum and PV areas. The degree of DTC correlated with the clinical severity of dementia as assessed by the clinical dementia rating (CDR). Mean diffusivity was diffusely and positively associated with the CDR scores. Fractional anisotropy of the PV areas was negatively associated with the CDR scores, suggesting a critical role of the lateral cholinergic pathways.

Introduction

Pathological characteristics of Alzheimer's disease (AD) are conventionally noted as cortical involvement with neurofibrillary tangles and senile plaques (Arnold et al., 1991). However, white matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. Decline in intelligence is associated with changes in white matter volume (Garde et al., 2005). White matter lesions may be predictors of neuropsychological deficits in post-stroke patients (Jokinen et al., 2005). AD patients with white matter changes at baseline show a rapid decline of cognitive function (de Leeuw et al., 2005).

Frontotemporal dementia (FTD) is characterized by early language dysfunction or personality change. Two types of pathological features can be found. In some patients, there is microvacuolation of upper cortical layers, and in others, there is gliosis of cortical and subcortical white matter (Neary et al., 2005). The topography of the pathological changes corresponds to the cognitive domains involved, being restricted to frontal and temporal regions (Rosen et al., 2002). A recent diffusion tensor imaging study showed significant white matter damage in the early phase of FTD (Borroni et al., 2007).

Vascular dementia includes a heterogeneous group of patients presenting cognitive impairment from various cerebrovascular lesions. Impairments in cognitive function are related to the location and extent of the vascular insult (Gold et al., 2005). Subcortical ischemic vascular dementia (SIVD) is a subtype of vascular dementia with small lacunes in the basal ganglia, thalamus, or subcortical white matter regions. White matter disruption measured by diffusion tensor imaging was correlated with executive dysfunction in patients with SIVD (O’Sullivan et al., 2004).

Both AD and FTD have pathological features of cortical neuron loss and have been considered to be primary degenerative processes in the neocortex (Pearson et al., 1985, Rogers and Morrison, 1985). However, white matter involvement was invariably found in either group of patients. It could be secondary to the degeneration of cortical neurons or due to primary pathology occurring in the white matter regions. On the other hand, SIVD has primary white matter lesions from ischemic injury.

Current magnetic resonance imaging (MRI) technology has made possible the in vivo assessment of white matter integrity by using diffusion tensor imaging (DTI). In normal white matter tissue, axons are regularly aligned and well myelinated. Thus, the random diffusion of water molecules is restricted to a predominant diffusion orientation. Fractional anisotropy (FA) estimates this preference and is used to assess fiber tract integrity and alignment so that normal white matter tissue shows high FA (Pierpaoli et al., 1996). Mean diffusivity (MD) is a measure of the average motion of water molecules, which is independent of tissue directionality. Normal white matter tissue has low MD (Basser and Pierpaoli, 1996). Diseases that disrupt the directionality of fiber tracts and the tissue integrity of brain white matter reduce FA and increase MD (Englund et al., 2004).

A number of DTI studies have examined AD (Bozzali et al., 2002, Choi et al., 2005, Naggara et al., 2006), mild cognitive impairment (Fellgiebel et al., 2006, Medina et al., 2006) and cognitive declines associated with chronic vascular disease or leukoaraosis (O'Sullivan et al., 2004). There are few studies, however, on non-AD forms of dementia (Yoshiura et al., 2006). Furthermore, it is not feasible to carry out cross-study comparisons across different types of dementia because published studies have been performed with variable platforms using different methods of analysis such as region of interest (ROI), histogram, or voxel-by-voxel approaches (Bozzali and Cherubini, 2007). Thus, we investigated white matter integrity with DTI in patients with amnesic mild cognitive impairment (MCI), AD, vascular dementia (VaD), and frontotemporal dementia (FTD). The aim was to explore patterns specific or common to different types of dementia, and to understand more about the white matter pathology of dementia on an image platform with a uniform analysis method.

Section snippets

Patients

We examined 10 patients with MCI, 30 with AD, 18 with SIVD, 7 with FTD and 20 control subjects (Table 1). All subjects received a comprehensive clinical examination including medical history, physical and neurological examination, laboratory investigation and brain MRI study. Patients with MCI and various dementias were evaluated with the Mini-Mental State Examination, the Clinical Dementia Rating scale (CDR), the Behavioral Pathology in Alzheimer's Disease Rating Scale, Lawton's Instrumental

Results

There was a significant group effect of age (F = 5.4, P < 0.01). A post hoc test showed that patients with FTD were younger than patients with AD and SIVD (both P < 0.05). However, the pairwise post hoc test showed no significant age effect between control subjects and patients with MCI or other dementias (all P > 0.05). There was no gender effect between groups (Pearson Chi-square = 4.82, P > 0.1). The severity of dementia was about equivalent (χ2 = 0.171, P > 0.5) as assessed by the Clinical Dementia Rating

Discussion

Previous DTI studies demonstrated associations of pathology in brain white matter with progression of cognitive deficits (de Leeuw et al., 2005, Fellgiebel et al., 2006, Yoshiura et al., 2002). Our study using DTI showed patterns of white matter abnormalities in patients with different types of dementia.

AD patients had diffusion tensor changes in both the anterior and posterior cerebral white matter, including the genu and the splenium of the corpus callosum. The splenium of the corpus callosum

Acknowledgement

The study was supported in part by a grant from National Taiwan University Hospital (NTUH 93A16-3) and in part by a grant from the Taiwan National Science Council (NSC 95-2314-B-144).

References (49)

  • SjöbeckM. et al.

    White matter mapping in Alzheimer's disease: a neuropathological study

    Neurobiology of Aging

    (2006)
  • YoshiuraT. et al.

    Cerebral white matter degeneration in frontotemporal dementia detected by diffusion-weighted magnetic resonance imaging

    Academic Radiology

    (2006)
  • ArnoldS.E. et al.

    The topographical and neuroanatomical distribution of neurofibrillary tangles and neurititc plaques in the cerebral cortex of patients with Alzheimer's disease

    Cerebral Cortex

    (1991)
  • BorroniB. et al.

    Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia

    Archives of Neurology

    (2007)
  • BozzaliM. et al.

    White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging

    Journal of Neurology, Neurosurgery & Psychiarty

    (2002)
  • BraccoL. et al.

    Alzheimer's disease: role of size and location of white matter changes in determining cognitive deficits

    Dementia and Geriatric Cognitive Disorders

    (2005)
  • BrunA. et al.

    A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study

    Annals of Neurology

    (1986)
  • ChoiS.J. et al.

    Diffusion tensor imaging of frontal white matter microstructure in early Alzheimer's disease: a preliminary study

    Journal of Geriatric Psychiatry and Neurology

    (2005)
  • de GrootJ.C. et al.

    Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study

    Annals of Neurology

    (2000)
  • de LeeuwF.E. et al.

    Progression of cerebral white matter lesions in Alzheimer's disease: a new window for therapy?

    Journal of Neurology, Neurosurgery & Psychiarty

    (2005)
  • DuanJ.H. et al.

    White matter damage of patients with Alzheimer's disease correlated with the decreased cognitive function

    Surgical and Radiologic Anatomy

    (2006)
  • EnglundE. et al.

    Diffusion tensor MRI post mortem demonstrated cerebral white matter pathology

    Journal of Neurology

    (2004)
  • FukuiT. et al.

    Do lesions involving the cortical cholinergic pathways help or hinder efficacy of donepezil in patients with Alzheimer's disease?

    Dementia and Geriatric Cognitive Disorders

    (2006)
  • GardeE. et al.

    Decline in intelligence is associated with progression in white matter hyperintensity volume

    Journal of Neurology, Neurosurgery & Psychiarty

    (2005)
  • Cited by (64)

    • Reduced fractional anisotropy of the genu of the corpus callosum as a cerebrovascular disease marker and predictor of longitudinal cognition in MCI

      2020, Neurobiology of Aging
      Citation Excerpt :

      A previous Rotterdam Study in patients with MCI with CVD found microstructural damage in the genu, internal and external capsule, and periventricular WM, but in those without CVD, deterioration was found along the hippocampal tract (Papma et al., 2014), suggesting that the anterior changes may be more specific to CVD. A consistent DTI change in the genu was also demonstrated in patients with subcortical vascular dementia (Chen et al., 2009) further supporting our use of FA-Genu. One would argue against using a specific tract instead of global DTI measures.

    • Neuroimaging in aging and neurologic diseases

      2019, Handbook of Clinical Neurology
    • Novel imaging techniques in cerebral small vessel diseases and vascular cognitive impairment

      2016, Biochimica et Biophysica Acta - Molecular Basis of Disease
    View all citing articles on Scopus
    1

    Dr. C.C. Lin is an equal first author.

    View full text