ReviewParietal cortex matters in Alzheimer's disease: An overview of structural, functional and metabolic findings
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].
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