1. Insular Cortex Morphometry in Alzheimer’s Disease and Mild Cognitive Impairment Khalil Thompson, Kwame Jackson, Armond Collins, Taylor Smith, Jeremy Cohen Ph.D, ADNI Xavier University of Louisiana Department of Psychology
Introduction
Procedure
Results
Alzheimer’s disease (AD) dementia is the final stage of a documented process that spans decades, but there is still a need for neuroimaging to capture anatomical changes related to these specific cellular processes.
Recent studies confirmed an ordered sequence of AD pathology that includes the insular cortex in Braak Stage III, while AD diagnosis coincides with Braak V & VI.
AD has been associated with both autonomic malfunction and insular pathology, which may explain why AD has effects on BP and central autonomic cardio-regulatory functions.
Physicians currently place the majority of their focus on the late stages, after the insula has already been affected and other structures, including frontal lobe, show significant atrophy.
Mild Cognitive Impairment (MCI) is a disorder of slight but noticeable and measurable decline in cognitive abilities, potentially coinciding with pre-clinical AD mechanisms.
Therefore, the purpose of this experiment was to identify a neural correlate that distinguishes MCI and AD.
It was predicted that insula volumes in AD would be smaller than MCI.
Additionally, it was expected that anterior insula would be more anomalous compared to the posterior insula.
There was a significant reduction in total insula volume in AD compared to MCI, F (1,19) = 7.014, p < 0.05.
There was a significant reduction in posterior insula volume (F (1,19) = , p < 0.01) but not in anterior volume (F (1,19) = 3.706, p > 0.05) in AD compared to MCI.
There was a positive correlation between the MMSE and right posterior insula volume, r (12) = 0.583, p < 0.05.
Discussion
Because of the preclinical autonomic effects seen in MCI patients (Royall, Gao, Kellogg, 2006), the data here suggest that anterior insula anatomical changes occur early in the disease process.
Posterior insular anatomy distinguishes between AD and MCI, and it appears that posterior insula is affected more substantially later in the disease course once full-blown AD symptoms are presented.
Insular cortex also has a high incidence of neuritic plaques and neurofibrillary tangles; with tangles relating to number of years of clinical dementia (Bonthius, Solodkin, Van Hoesen, 2005).
This data implicates the insular cortex as a neural correlate of degenerative cognitive and behavioral deficits associated with MCI and AD.
Overall, AD is the final stage of a process that spans decades and insular cortex is affected at a preclinical stage of the disease process, specifically during the progression of MCI (Braak & Braak, 1991).
Future studies should assess whether insular morphometry could add an additional level to the diagnostic process to identify brain changes of MCI, prior to other significant cognitive decline.
Doing so could aid earliest intervention to slow the progression of brain atrophy and cognitive decline.
Figure 1) Sagittal section of insula with AIV (green) and PIV (red) ROI tracings after geometric sub-region algorithm was applied in BIJ
Figure 2) Coronal section of insula with AIV (green) and PIV (red) ROI tracings after geometric sub-region algorithm was applied in BIJ
Data
Region
Diagnoses F p
MCI AD
Left Anterior
(487.11)
(544.83)
3.706
.069
Right Anterior
(599.59)
(616.99)
Left Posterior
(340.65)
(341.26)
11.787
.003
Right Posterior
(415.78)
(468.60)
Left Total
(780.46)
(810.49)
7.014
.016
Right Total
(995.55)
( )
Table 1: Insular ROI mean volumes (standard deviations) in mm3 for MCI and AD
Methods
Subjects were 14 AD (M=7, F=7) & 9 MCI (M=5, F=4) from ADNI
AD mean age was (10.25) & MCI mean age was (6.28)
The mean Mini Mental State Exam scores were 21.5 (2.74) in AD & (1.67) in MCI.
Regions of interest (ROI) were Total Insular Volume (TIV), Anterior Insular Volume (AIV), and Posterior Insular Volume (PIV).
AIV, and PIV ROIs were created by using a geometric algorithm built into BrainImageJava (BIJ) (Ng, et al., 2001).
A computer-guided cursor was used to trace the insula in every sagittal image that included insula to establish the anterior and posterior boundaries.
The anterior boundary was designated by the anterior limiting sulcus between the insula and orbital frontal cortex.
The posterior boundary was defined as the junction of the superior and inferior circular sulci, anterior to Hechel’s gyrus.
Measurements of each ROI (in mm3) were computed using sagittal and coronal planes of view in BIJ with no warping of the images.
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