Hum Brain Mapp. 2013 Oct;34(10):2484-93. doi: 10.1002/hbm.22078.

Regional cerebral blood flow and FDG uptake in asymptomatic HIV-1 men.

Towgood KJ, Pitkanen M, Kulasegaram R, Fradera A, Soni S, Sibtain N, Reed LJ, Bradbeer C, Barker GJ, Dunn JT, Zelaya F, Kopelman MD.

Department of Psychological Medicine, King’s College London, Institute of Psychiatry, London, United Kingdom, SE5 8AF.

 

Abstract

Despite advances in the treatment of patients with human immunodeficiency virus (HIV), HIV-associated neurocognitive disorder occurs in 15-50% of HIV-infected individuals, and may become more apparent as ageing advances. In the present study we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in medically and psychiatrically stable HIV-1-infected participants in two age-groups. Positron emission tomography (PET) and magnetic resonance imaging (MRI)-based arterial spin labeling (ASL) were used to measure rCMRglc and rCBF, respectively, in 35 HIV-infected participants and 37 HIV-negative matched controls. All participants were currently asymptomatic with undetectable HIV-1 viral loads, without medical or psychiatric comorbidity, alcohol or substance misuse, stable on medication for at least 6 months before enrolment in the study. We found significant age effects on both ASL and PET with reduced rCBF and rCMRglc in related frontal brain regions, and consistent, although small, reductions in rCBF and rCMRglc in the anterior cingulate cortex (ACC) in HIV, a finding of potential clinical significance. There was no significant interaction between HIV status and the ageing process, and no significant HIV-related changes elsewhere in the brain on PET or ASL. This is the first paper to combine evidence from ASL and PET method in HIV participants. These finding provide evidence of crossvalidity between the two techniques, both in ageing and a clinical condition (HIV).

Copyright © 2012 Wiley Periodicals, Inc.

KEYWORDS: ASL; HIV; PET; ageing; glucose uptake; rCBF

PMID: 22496057

 

Supplements:

Over the past decade, the developments made in treating people with human immunodeficiency virus (HIV) have greatly improved their quality of life and life expectancy.  However, the nature of asymptomatic HIV-associated minor neurocognitive disorder (HAND) remains unclear.

In an initial study, we examined the occurrence of neuropsychological and magnetic resonance imaging (MRI) changes in medically and psychiatrically stable HIV-1 infected patients.  These patients were on highly active antiretroviral treatment (HAART), and consisted of groups of younger (aged between 20 and 40) and older (aged between 50 and 75) patients.  Comparisons were made with 20 age- and education-matched younger and 22 matched older HIV-negative men.  The participants were free of medical or psychiatric comorbidity, and did not misuse either alcohol or substances, i.e. they were a selective HIV group, in whom these factors had been excluded.

There were significant effects of the ageing process on memory performance, and grey and white matter volumes on MRI.  However, the HIV-positive and HIV-negative groups did not differ on the neuropsychological tests after an appropriate Bonferroni correction; and there was not any statistically significant interaction between the ageing process and HIV on these measures.  Importantly however, we did find reduced grey matter volume in the HIV-positive participants within the medial and superior frontal cortex in both the younger and the older groups.

In a further study, we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in these patients.  rCBF was determined using 18-fluoro-deoxy-glucose positron emission tomography (PET).  rCMRglc was determined using MRI-based arterial spin labelling (ASL).

There were striking effects of age on both the PET and ASL measures with reduced rCBF and rCMRglc in frontal brain regions.  Importantly, there were also consistent, although small, reductions in rCBF and rCMRglc in the anterior cingulate cortex in the HIV groups, both younger and older.

The anterior cingulate is a brain region involved in behavioural initiation, motivation, and goal-directed behaviour.  It has also been hypothesised to play a role in the regulation of emotion; and pathology in this brain region has previously been found to produce behavioural changes such as disinhibition and impulsivity.  It has previously been suggested that neuronal damage, associated with HIV infection, might affect a network including the anterior cingulate.  Alternatively, it could be argued that impaired anterior cingulate function might predispose HIV-infected individuals to engage in behaviour which increases their risk of secondary infection and cognitive impairment.  However, the possibility that damage to this region reflects the effect of HAART medication needs also to be excluded.

The importance of these investigations are:

i) They demonstrate that, in participants who are stable on treatment and do not misuse either alcohol or substances, nor have any concomitant medical or psychiatric disorder, HIV does not generally impair cognitive function.

ii) However, we have identified some changes in HIV, notably in the superior and medial frontal grey matter on MRI, and in the anterior cingulate on PET and ASL.  These changes may be predictive of future cognitive and/or behavioural change, particularly in older HIV-infected people, and we are currently investigating this in a longitudinal follow-up study.

iii) Ours is the first study, we believe, to employ both PET and ASL techniques in a clinical population.  We have obtained consistent findings across the two methods in examining regional cerebral blood flow and regional metabolic glucose uptake, both in examining the effects of HIV and also the effects of the ageing process itself.

 

References

Towgood, K.J., Pitkanen, M., Kulasegaram, R., Fradera, A., Kumar, A., Soni, S., Sibtain, N.A., Reed, L., Bradbeer, C., Barker, G.J., Kopelman, M.D. (2012) Mapping the brain in younger and older asymptomatic HIV-1 men: frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex, 48, 230-241.

Towgood, K.J., Pitkanen, M., Kulasegaram, R., Fradera, A., Soni, S., Sibtain, N., Reed, L., Bradbeer, C., Barker, G.J., Dunn, J.T., Zelaya, F., Kopelman, M.D. (2013) Regional cerebral blood flow and FDG uptake in asymptomatic HIV-1 men. Human Brain Mapping, 34, 2484-93.

 

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