Global gray matter atrophy associated with neurocognitive...

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Global gray matter atrophy associated with neurocognitive impairment in HIV P. Manori De Alwis , Bryan Smith, Avindra Nath, Daniel S. Reich, Govind Nair

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?

Presentator
Presentatienotities
Sclafani - 31 HIV+ and 10 high-risk controls. Elovaara - 72 HIV+ and 34 controls.

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

Presentator
Presentatienotities
(ANI) – 1 SD below 2 cognitive domains without a symptomatic or observable functional impairment. (MND) – 1 SD below 2 cognitive domains with mild symptomatic or functional impairment. (HAD) – 2 SD below 2 cognitive domains with concomitant impairment in activities of daily living.

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

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.

Presentator
Presentatienotities
Cortical folding should not contribute to differences that are picked up, so the group comparisons are done on an inflated surface. Can compare regions instead of individual pixels Volume registered with Talairach atlas, B1 bias field calculated and intensity at each voxel is divided by bias field at that location to remove effect of the bias field. Uses a cortical surface-based atlas based on average folding patterns mapped to a sphere. Surfaces from individuals can be aligned with this atlas with a high-dimensional nonlinear registration algorithm. The registration is based on aligning the cortical folding patterns and so directly aligns the anatomy instead of image intensities.

FreeSurfer Outputs & QAing

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

Presentator
Presentatienotities
Yay!!!!

End