Microstructural brain abnormalities in HIV+ individuals with or without chronic marijuana use.

Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2004-

Brain/*pathology ; Cognition Disorders/*pathology ; HIV Infections/*pathology ; Marijuana Use/*pathology; Adolescent ; Adult ; Aged ; Brain/diagnostic imaging ; Cognition Disorders/diagnostic imaging ; Cognition Disorders/etiology ; Diffusion Tensor Imaging ; Female ; HIV Infections/complications ; HIV Infections/diagnostic imaging ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; White Matter/diagnostic imaging ; White Matter/pathology ; Young Adult

Objective: Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+.
Method: Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions.
Results: Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001-0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus.
Conclusions: Our findings suggest that, except in the globus pallidus, chronic MJ use had no additional negative influence on brain microstructure or neurocognitive deficits in HIV+ individuals. However, lower AD in the uncinate fasciculus of MJ users suggests axonal loss in this white matter tract that connects to cannabinoid receptor rich brain regions that are involved in verbal memory and emotion. Furthermore, the greater than normal age-dependent FA declines in the white matter tracts and globus pallidus in MJ users suggest that older chronic MJ users may eventually have lesser neuronal integrity in these brain regions.

Mol Neurodegener. 2014 Dec 18;9:58. (PMID: 25523827)
J Pharmacol Exp Ther. 2018 Oct;367(1):49-58. (PMID: 30026298)
J Biol Chem. 2010 Jan 15;285(3):1616-26. (PMID: 19910459)
mBio. 2019 May 28;10(3):. (PMID: 31138753)
Ann Clin Transl Neurol. 2015 Jan;2(1):12-21. (PMID: 25642430)
J Clin Pharmacol. 2002 Nov;42(S1):71S-81S. (PMID: 12412839)
Life Sci. 2005 Aug 19;77(14):1711-22. (PMID: 15964028)
Neuroimage Clin. 2015 Apr 02;8:117-25. (PMID: 26106535)
J Neuroimmune Pharmacol. 2021 Jun;16(2):334-345. (PMID: 32323137)
J Gerontol. 1982 May;37(3):323-9. (PMID: 7069156)
Cannabis Cannabinoid Res. 2018 Mar 01;3(1):56-65. (PMID: 29607411)
Handb Clin Neurol. 2018;152:229-264. (PMID: 29604980)
Neuropharmacology. 2018 Jan;128:269-281. (PMID: 29061509)
J Magn Reson Imaging. 2010 Nov;32(5):1045-53. (PMID: 21031507)
Br J Pharmacol. 2015 Oct;172(19):4603-14. (PMID: 24571443)
Biol Psychiatry. 2016 Apr 1;79(7):557-67. (PMID: 26858214)
AIDS. 2018 Feb 20;32(4):419-429. (PMID: 29194121)
Am J Drug Alcohol Abuse. 2017 Jan;43(1):103-110. (PMID: 27398989)
Neuroimage. 2009 Jun;46(2):486-99. (PMID: 19385016)
Hum Brain Mapp. 2019 Oct 15;40(15):4370-4380. (PMID: 31271489)
Eur Arch Psychiatry Clin Neurosci. 2019 Feb;269(1):5-15. (PMID: 30671616)
PLoS One. 2012;7(3):e32995. (PMID: 22479354)
Psychopharmacology (Berl). 2016 Oct;233(19-20):3627-37. (PMID: 27503373)
J Neuroimmune Pharmacol. 2016 Mar;11(1):192-213. (PMID: 26607731)
Neurology. 2007 Oct 30;69(18):1789-99. (PMID: 17914061)
Dev Neuropsychol. 2010;35(3):257-77. (PMID: 20446132)
AJNR Am J Neuroradiol. 2017 Aug;38(8):1510-1519. (PMID: 28596189)
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Mar 1;8(3):273-8. (PMID: 7859139)
J Acquir Immune Defic Syndr. 2020 Jan 1;83(1):56-64. (PMID: 31809361)
Neuropsychology. 2003 Jul;17(3):410-9. (PMID: 12959507)
Clin Infect Dis. 2020 Jan 1;70(1):140-143. (PMID: 31074488)
JAMA Psychiatry. 2016 Mar;73(3):292-7. (PMID: 26842658)
Exp Clin Psychopharmacol. 2012 Oct;20(5):420-429. (PMID: 22731735)
AIDS. 2018 Jul 31;32(12):1661-1667. (PMID: 29746297)
J Clin Invest. 2013 Jul;123(7):2816-31. (PMID: 23934130)
Addiction. 2018 Feb;113(2):257-265. (PMID: 28734078)
Br J Pharmacol. 2009 Aug;157(7):1225-31. (PMID: 19558543)
J Neuroimmune Pharmacol. 2020 Dec;15(4):765-779. (PMID: 32445005)
Brain. 2012 Jul;135(Pt 7):2245-55. (PMID: 22669080)
J Neuroimmune Pharmacol. 2009 Dec;4(4):430-47. (PMID: 19768553)
J Neuroimmune Pharmacol. 2018 Dec;13(4):509-522. (PMID: 30225549)
JAMA Psychiatry. 2018 Jun 1;75(6):585-595. (PMID: 29710074)
Magn Reson Med. 2007 Apr;57(4):688-95. (PMID: 17390365)
Neurology. 2016 Apr 12;86(15):1425-1432. (PMID: 26911637)
Nat Rev Neurol. 2016 May;12(5):309. (PMID: 27080521)
AIDS Care. 2016;28(5):628-32. (PMID: 26694807)
Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):E2657-64. (PMID: 22927402)
J Neuroimmunol. 2004 Dec;157(1-2):147-52. (PMID: 15579292)
J Neurosci. 2011 Oct 19;31(42):15195-204. (PMID: 22016553)
Drug Alcohol Depend. 2017 Jan 01;170:120-127. (PMID: 27889592)
Neuroimage Clin. 2016 Jun 08;12:47-56. (PMID: 27408790)
J Neuroimmune Pharmacol. 2006 Mar;1(1):65-76. (PMID: 18040792)
Brain Res. 2005 Feb 9;1034(1-2):11-24. (PMID: 15713255)
J Clin Exp Neuropsychol. 2011 Aug;33(7):735-52. (PMID: 21480022)
Cochrane Database Syst Rev. 2013 Apr 30;(4):CD005175. (PMID: 23633327)
J Neuroimmune Pharmacol. 2008 Dec;3(4):265-74. (PMID: 18709469)
Blood. 2008 Feb 15;111(4):2062-72. (PMID: 18003888)
Comput Methods Programs Biomed. 2006 Feb;81(2):106-16. (PMID: 16413083)
J Int Neuropsychol Soc. 2007 Jan;13(1):1-11. (PMID: 17166298)
Exp Clin Psychopharmacol. 2011 Apr;19(2):154-72. (PMID: 21463073)
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16913-8. (PMID: 25385625)
AIDS Behav. 2017 Jul;21(7):2005-2013. (PMID: 28456895)
J Neuroimmune Pharmacol. 2010 Sep;5(3):456-68. (PMID: 20549374)
Addict Biol. 2019 Nov;24(6):1235-1244. (PMID: 30239074)
Magn Reson Med. 2006 Feb;55(2):302-8. (PMID: 16408263)
Neuroimage. 2009 Aug 15;47(2):618-27. (PMID: 19398016)

1R01DA035659 United States DA NIDA NIH HHS; K02-DA16991 United States DA NIDA NIH HHS; 1U54NS56883 United States NS NINDS NIH HHS; U54 NS056883 United States NS NINDS NIH HHS; 2K24-DA16170 United States DA NIDA NIH HHS; K02 DA016991 United States DA NIDA NIH HHS

Keywords: Cognition; DTI; Diffusivity; Fractional anisotropy; HIV; Marijuana

Date Created: 20200808 Date Completed: 20210702 Latest Revision: 20240330

20240330

PMC7409464

10.1186/s12974-020-01910-5

32758262