Global gray matter atrophy associated with neurocognitive...
Transcript of Global gray matter atrophy associated with neurocognitive...
Global gray matter atrophy associated with neurocognitive
impairment in HIV
P. Manori De Alwis, Bryan Smith, Avindra Nath, Daniel S. Reich, Govind Nair
Our HAND Study
Primary Objective:Characterize the natural course of HAND in subjects with low CD4 nadir (<200 cells/mm3) and prolonged plasma HIV virologicsuppression (<200 copies/mL).
Imaging: PET
Psychiatric Evaluation
Neurological Exam
Imaging:MRI
Neuropsychological Testing
Blood:metabolic,
inflammatory, virologic
CSF:metabolic,
inflammatory, virologic
Why study volume?Pre-HAART era: marked differences betweenHIV- and HIV+• Greater global atrophy and GM volume loss. Sclafani et al. 1997
• Those with infections for longer periods had more severe and morefrequent abnormalities – central and cortical atrophy, brain stem atrophy, and cerebellar atrophy. Elovaara et al. 1990
• Significant correlations between MRI ratios and many NP tests. Hestad et al. 1993
Do these differences persist after HAART?
Do these volume differences correlate with NP impairment, specifically HAND?
Present Cohort
(Demographically Matched HIV-)
Controls(HIV+/HAND-)
HIV(HIV+/HAND+)
HANDn 17 55 14
Average Age (STDev) 47 (9) 51 (8) 51 (8)
% Male 53 65 50Disease Duration in yrs
(STDev)18.4 (8.9) 18.5 (7.1)
CD4 at time of Scan 875 (291) 577 (278) 608 (384)
Neuropsych Evaluation
• The CHARTER battery of tests and few others– attention/working memory– abstraction/executive functioning– memory (learning; recall)– speed of information processing– sensory-perceptual, motor skills
MRI Method
• 3T Philips scanner with an 8-channel head coil.
• Sequences: proton density, SWI, FLAIR, MPRAGE, and diffusion tensor imaging.
MPRAGEi.e. Magnetization-Prepared Rapid Acquisition with Gradient Echo
• T1-weighted image• 1mm isotropic
FreeSurfer Segmentation1. Surface-based stream (Cortical analysis pipeline)
2. Volume-based stream (Subcortical analysis) -high dimensional nonlinear volumetric alignment to the Talairach atlas, and labeling for each of the volumes
(Left) Skull stripped image.
(Middle) White matter segmentation.
(Right) Surface between white and gray (yellow line) and between gray and pial(red line) overlaid on the original volume.
Trends in Total Gray Matter across groups
Total White Matter
One-Way Anovap= 0.61
One-Way Anovap=0.11
T-testsControl v HAND p= 0.08
Total Gray Matter
HIV v HAND p= 0.09Control v HIV p= 0.79
Cortical Gray Volume
One-Way Anovap=0.09
T-testsControl v HIV p=0.95Control v HAND p=0.08HIV v HAND p=0.06
Regional Gray Matter Volumes between cohorts
One-Way Anovap=0.25
Subcortical Gray Volume
T-testsControl v HIV p=0.16Control v HAND p=0.12HIV v HAND p=0.46
Cortical Gray Volume
Modeling cortical volume differencesRegions where cortical volume differs between…
Cont
rol v
HAN
DH
IV v
HAN
DCo
ntro
l v H
IV
Control v HIV p=0.95
T-testsControl v HAND p=0.08HIV v HAND p=0.06
Age and Gray Matter Correlation: Across all groups
Pearson r = - 0.31, p-value= 0.004 Pearson r = - 0.43, p-value <0.0001
Pearson r = - 0.33p-value = 0.002
Tota
l Gra
y
Cort
ical
Gra
y
Subc
ortic
al G
ray
No significant differences between groups
Tota
l Gra
y
Cort
ical
Gra
y
Subc
ortic
al G
ray
p= 0.66
p= 0.37p= 0.7
Preliminary Conclusions
• Lower total and cortical GM volumes in HAND compared to that in HIVs and controls.
• Ongoing analysis will assess correlations between specific brain regions and individual neurocognitive scores.
• Additional recruitment of HAND and Control subjects will help better substantiate group differences.
Thank you!
NINDSDaniel S. Reich
Govind NairAvindra NathBryan SmithSally Smith
Peter Siyahhan Julnes
NIAStanley Rapoport
NIMHJoseph Snow
Angela SummersTalia Shirazi
NIAIDChuen-Yen Lau
Ed Tramont