Abstract
Regions affected late in neurodegenerative disease are thought to be anatomically connected to regions affected earlier. The subcallosal medial prefrontal cortex (SMPC) has connections with the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and hippocampus (HC), which are regions that may become atrophic in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). We hypothesized that the SMPC is a common site of frontal atrophy in the FTLD subtypes and in AD. The volume of the SMPC, DLPFC, OFC, HC, and entorhinal cortex (EC) were manually delineated for 12 subjects with frontotemporal dementia (FTD), 13 with semantic dementia (SD), 9 with progressive nonfluent aphasia (PNFA), 10 AD cases, and 13 controls. Results revealed significant volume loss in the left SMPC in FTD, SD, and PNFA, while the right SMPC was also atrophied in SD and FTD. In AD a non significant tendency of volume loss in the left SMPC was found (p = 0.08), with no volume loss on the right side. Results indicated that volume loss reflected the degree of brain connectivity. In SD and AD temporal regions displayed most atrophy. Among the frontal regions, the SMPC (which receives the strongest temporal projections) demonstrated most volume loss, the OFC (which receives less temporal projections) less volume loss, while the DLPFC (which is at multisynaptic distance from the temporal regions) demonstrated no volume loss. In PNFA, the left SMPC was atrophic, possibly reflecting progression from the left anterior insula, while FTD patients may have had SMPC atrophy at the initial stages of the disease. Atrophy of the SMPC may thus be affected by either initial temporal or initial frontal atrophy, making it a common site of frontal atrophy in the dementia subtypes investigated.
Highlights
In recent years the view that regional atrophy in dementia results from damage to particular brain networks has received increased attention
The greatest gray matter loss was found in the orbitofrontal cortex (OFC), subcallosal medial prefrontal cortex (SMPC), and HC with a loss of approximately 25% compared to control group (CTL) subjects
This study explored the hypothesis that the SMPC may be vulnerable to atrophy in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) because of its anatomical connections with frontal and temporal regions that become atrophic in these diseases
Summary
In recent years the view that regional atrophy in dementia results from damage to particular brain networks has received increased attention. The underlying mechanism of the connection hypothesis is that molecular pathologies such as β-amyloid, tau, α-synuclein, and TDP-43 aggregate and progress through specific anatomical connections or brain networks (Seeley et al, 2009; Raj et al, 2012). Support for this assumption in both AD and FTLD has been presented in a large study by Seeley et al (2009). On the basis of the strength of connectivity found in this model several networks were proposed that in subsequent analysis was shown to correspond well with Seeley’s assumption of network-specific progression of atrophy in FTLD and AD (Raj et al, 2012)
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