Review
Parietal cortex matters in Alzheimer's disease: An overview of structural, functional and metabolic findings

https://doi.org/10.1016/j.neubiorev.2011.06.009Get rights and content

Abstract

Atrophy of the medial temporal lobe, especially the hippocampus and the parahippocampal gyrus, is considered to be the most predictive structural brain biomarker for Alzheimer's Dementia (AD). However, recent neuroimaging studies reported a possible mismatch between structural and metabolic findings, showing medial temporal lobe atrophy and medial parietal hypoperfusion as biomarkers for AD. The role of the parietal lobe in the development of AD is only recently beginning to attract attention. The current review discusses parietal lobe involvement in the early stages of AD, viz. mild cognitive impairment, as reported from structural, functional, perfusion and metabolic neuroimaging studies. The medial and posterior parts of the parietal lobe seem to be preferentially affected, compared to the other parietal lobe parts. On the basis of the reviewed literature we propose a model showing the relationship between the various pathological events, as measured by different neuroimaging techniques, in the development of AD. In this model myelin breakdown is a beginning of the chain of pathological events leading to AD pathology and an AD diagnosis.

Highlights

• Imaging studies in Alzheimer's disease have focussed on medial temporal lobe changes. • Metabolic studies show the importance of the parietal lobe. • We review evidence of involvement of the parietal lobe from various imaging studies. • The posterior cingulate gyrus is most commonly affected in early Alzheimer's disease. • A disease model, based on the parietal lobe, highlights the role of myelin breakdown.

Introduction

Alzheimer's disease (AD), the most common cause of dementia, is characterized by an insidious decline in memory, later affecting language, visuospatial perception, arithmetic abilities and executive functioning. Behavioral and psychiatric symptoms have also been frequently reported (Cummings, 2004). AD is characterized by both the accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles (tau pathology) leading to regional neuronal loss, cortical atrophy and cognitive decline (Braak and Braak, 1991, Braak and Braak, 1996). Histological studies have shown that neurofibrillary tangle formation occurs in a well-defined order, starting in the medial temporal lobe early in the disease and subsequently progressing towards the lateral temporal and association parietal cortices, the prefrontal cortices and finally the motor and sensory areas (Braak and Braak, 1996). By contrast, amyloid plaques first affect the posterior association cortices in the earliest stage of the disease. The medial temporal lobe areas might then be affected, but this is not very common in the early stages of AD (Braak and Braak, 1991, Braak and Braak, 1996, Thal et al., 2002).

The amyloid cascade hypothesis has been dominating AD research to date (Korczyn, 2008), stating that extracellular amyloid plaques formed by aggregates of amyloid beta (Abeta) peptide, are central to the AD pathology. In view of the evidence that amyloid deposition most commonly starts in the association neocortex (Braak and Braak, 1991, Braak and Braak, 1996, Thal et al., 2002), it is therefore rather surprising that the extant literature mainly focuses on pathology in the medial temporal lobe.

While different neuroimaging methods have shown that hippocampal and parahippocampal atrophy could predict conversion from MCI to AD (de Leon et al., 2007, Dickerson and Sperling, 2009, Echavarri et al., 2010, Jacova et al., 2008, van de Pol et al., 2009), the results so far have been equivocal. Medial temporal lobe atrophy has a low specificity, since it has also been observed in patients with other neurodegenerative diseases, such as Lewy Body dementia or Parkinson Disease (Barkhof et al., 2007) and even in healthy aging (Kaye et al., 1997, Raz et al., 2005). Besides grey matter atrophy, loss of regional white matter tissue in the medial temporal lobe areas (Jovicich et al., 2009, Naggara et al., 2006, Salat et al., 2009) has also been associated with AD. Functional imaging studies have shown that medial temporal lobe hyperactivation could be a possible biomarker for AD.

Metabolic imaging studies, however, have revealed a major discrepancy with the above structural and functional studies. Metabolic dysfunction is most frequent reported in tempoparietal association areas, in which hypometabolism in the medial parietal areas appears to be more accurate in discriminating AD patients from control participants (Imabayashi et al., 2004, Ishii et al., 2005, Jagust et al., 2002, Villain et al., 2010b). As for metabolic changes in the medial temporal lobe regions, the findings are less clear, suggesting that the temporal lobe is of less value (Encinas et al., 2003) and that metabolic changes in the medial temporal lobe areas are a better predictor than metabolic changes in the medial parietal areas (Caroli et al., 2007, Karow et al., 2010, Nobili et al., 2009). The medial parietal areas are considered to be the centre of metabolic changes (Jagust et al., 2002, Villain et al., 2010b, Zhang et al., 2011). Thus, there might be a mismatch between structural and metabolic findings (Buckner et al., 2005, Caroli et al., 2010, Hunt et al., 2007, Ishii et al., 2005, Klunk et al., 2004, Matsuda, 2007, Villain et al., 2010b). Understanding this mismatch requires a better comprehension of the relevance of the posterior association areas and their connectivity with the rest of the brain.

This overview summarizes the evidence of structural, functional and metabolic changes in MCI or prodromal AD patients based on the recent neuroimaging literature, with a special focus on posterior association regions, more specifically the parietal lobe areas. Our review of the literature also investigated which parietal region appears to be the most relevant in the development of AD, based on the research results that have been reported.

Section snippets

Search strategy and selection criteria

Research papers dating from January 2000 to September 2010 were identified in PubMed using the following search terms: {“mild cognitive impairment” or “prodromal Alzheimer” or “predementia Alzheimer”} and {“parietal” or “precuneus” or “posterior cingulate” or “retrosplenial”} and depending on the imaging technique reviewed: {“grey/gray matter” or “white matter” or “functional MRI” or “SPECT” or “PET”, or “metabolic”}. Searches were limited to papers written in English. Studies that solely

Structure of this review

We first summarize the neuroanatomy and functions of the parietal lobe. Then we review the results of the semi-systematic literature search, categorized by neuroimaging technique: structural, functional and metabolic neuroimaging studies. By taking this approach, we did not aim to play down the importance of the medial temporal lobe, but we wanted to highlight the high relevance of the parietal lobe in the earliest stages of the disease. We also wanted to examine which parietal area is most

Parietal lobe structure

The parietal lobe is the region of the cerebral cortex underlying the parietal skull bone. The anterior border of the parietal lobe is formed by the central sulcus and the marginal ramus. The posterior border can be defined by a line along the sulci from the parieto-occipital sulcus into the preoccipital notch. The ventral border can be defined by the insula and a line from the tip of the lateral fissure perpendicular to the curvilinear line from the parieto-occipital sulcus towards the

Grey matter studies

Table 1 (see Supplemental Data) summarizes the findings with respect to grey matter loss in the parietal lobe in MCI patients. Most studies (n = 10 out of 20) so far have used a voxel-based morphometry (VBM) approach, and far fewer have applied cortical thickness analyses (n = 6), a technique that gained popularity in recent years.

Studies comparing MCI patients with controls at one particular time point have reported varying results. Grey matter loss in MCI groups has been found in the following

Involvement of the parietal lobe in various neuroimaging studies in early AD

This review examined studies of the involvement of the parietal lobe areas in early AD. For years the medial temporal lobe has been the main research region of interest, because of the good predictive value of structural measures derived from this region in MRI studies. In recent years, however, metabolic imaging results have slowly shifted the focus towards the posterior association areas, because of the assumed mismatch with the structural MRI findings discussed above.

Two main conclusions

Funding

This work was supported by a grant from the FP6 EU programme Marie Curie Actions [MEST-CT-2005-020589].

References (201)

  • S. Caspers et al.

    The human inferior parietal cortex: cytoarchitectonic parcellation and interindividual variability

    Neuroimage

    (2006)
  • K. Chen et al.

    Twelve-month metabolic declines in probable Alzheimer's disease and amnestic mild cognitive impairment assessed using an empirically pre-defined statistical region-of-interest: findings from the Alzheimer's Disease Neuroimaging Initiative

    Neuroimage

    (2010)
  • G. Chetelat et al.

    Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study

    Neuroimage

    (2005)
  • J.C. Culham et al.

    Neuroimaging of cognitive functions in human parietal cortex

    Curr. Opin. Neurobiol.

    (2001)
  • S. De Santi et al.

    Hippocampal formation glucose metabolism and volume losses in MCI and AD

    Neurobiol. Aging

    (2001)
  • B.C. Dickerson et al.

    Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: insights from functional MRI studies

    Neuropsychologia

    (2008)
  • K. Dohnel et al.

    Neural correlates of emotional working memory in patients with mild cognitive impairment

    Neuropsychologia

    (2008)
  • A.M. Fjell et al.

    CSF biomarker pathology correlates with a medial temporo-parietal network affected by very mild to moderate Alzheimer's disease but not a fronto-striatal network affected by healthy aging

    Neuroimage

    (2010)
  • A. Forsberg et al.

    PET imaging of amyloid deposition in patients with mild cognitive impairment

    Neurobiol. Aging

    (2008)
  • R. Goekoop et al.

    Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study

    Neuroimage

    (2004)
  • J. Gottlieb

    From thought to action: the parietal cortex as a bridge between perception, action, and cognition

    Neuron

    (2007)
  • C. Grefkes et al.

    Human medial intraparietal cortex subserves visuomotor coordinate transformation

    Neuroimage

    (2004)
  • C. Grefkes et al.

    Crossmodal processing of object features in human anterior intraparietal cortex: an fMRI study implies equivalencies between humans and monkeys

    Neuron

    (2002)
  • A. Hamalainen et al.

    Increased fMRI responses during encoding in mild cognitive impairment

    Neurobiol. Aging

    (2007)
  • A. Hamalainen et al.

    Voxel-based morphometry to detect brain atrophy in progressive mild cognitive impairment

    Neuroimage

    (2007)
  • K. Hirao et al.

    The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT

    Neuroimage

    (2005)
  • C. Huang et al.

    Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment

    Neuroimage

    (2003)
  • C. Huang et al.

    Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment

    BMC Neurol.

    (2002)
  • A. Hunt et al.

    Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease

    Psychiatry Res.

    (2007)
  • M. Husain et al.

    Space and the parietal cortex

    Trends Cogn. Sci.

    (2007)
  • C.R. Jack et al.

    Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade

    Lancet Neurol.

    (2010)
  • H.I.L. Jacobs et al.

    Atrophy of the parietal lobe in preclinical dementia

    Brain Cogn.

    (2011)
  • M. Alegret et al.

    Brain perfusion correlates of visuoperceptual deficits in mild cognitive impairment and mild Alzheimer's disease

    J. Alzheimers Dis.

    (2010)
  • D. Anchisi et al.

    Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease

    Arch. Neurol.

    (2005)
  • L.G. Apostolova et al.

    Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease

    Arch. Neurol.

    (2007)
  • A. Bakkour et al.

    The cortical signature of prodromal AD: regional thinning predicts mild AD dementia

    Neurology

    (2009)
  • M.L. Balthazar et al.

    Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

    Eur. J. Neurol.

    (2009)
  • F. Barkhof et al.

    The significance of medial temporal lobe atrophy: a postmortem MRI study in the very old

    Neurology

    (2007)
  • G. Bartzokis

    Alzheimer's disease as homeostatic responses to age-related myelin breakdown

    Neurobiol. Aging

    (2009)
  • S. Bennett et al.

    Oxidative stress in vascular dementia and Alzheimer's disease: a common pathology

    J. Alzheimers Dis.

    (2009)
  • A.L. Bokde et al.

    Altered brain activation during a verbal working memory task in subjects with amnestic mild cognitive impairment

    J. Alzheimers Dis.

    (2010)
  • A.L. Bokde et al.

    Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment

    Brain

    (2006)
  • B. Bosch et al.

    Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance

    Neurobiol. Aging

    (2010)
  • M. Bozzali et al.

    The contribution of voxel-based morphometry in staging patients with mild cognitive impairment

    Neurology

    (2006)
  • H. Braak et al.

    Neuropathological stageing of Alzheimer-related changes

    Acta Neuropathol. (Berl)

    (1991)
  • H. Braak et al.

    Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis

    Acta Neuropathol. (Berl)

    (1996)
  • R.L. Buckner et al.

    The brain's default network: anatomy, function, and relevance to disease

    Ann. N. Y. Acad. Sci.

    (2008)
  • R.L. Buckner et al.

    Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory

    J. Neurosci.

    (2005)
  • S. Burgmans et al.

    Multiple indicators of age-related differences in cerebral white matter and the modifying effects of hypertension

    Neuroimage

    (2009)
  • R. Cabeza et al.

    The parietal cortex and episodic memory: an attentional account

    Nat. Rev. Neurosci.

    (2008)
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