Journal Article

Low CD4+ Count Increases the Negative Effect of APOE-4 on Memory


There are concerns among older persons living with HIV that their risk for Alzheimer’s disease might be increased. One factor that can increase risk is the presence of the APOE-4 gene.  

From 15 to 25% of persons living with and without HIV carry one copy of the APOE-4 gene.  This gene can increase by 2-3 times the risk of Alzheimer’s disease and possibly lower the age of onset.  This study addresses if those with HIV and APOE-4 can be at higher risk for memory problems.

In this study 100 older persons with HIV were evaluated, and 26 were carriers of APOE-4.  All were evaluated with MRI for abnormalities in the brain and were tested, as well, for memory performance.  Also, current and past CD4+ levels were assessed among the HIV positive study group. Those with APOE-4 were found to have poorer memory performance.  However, this was particularly true for those in the HIV group with a low CD4+ count nadir.  With this information the authors suggest that this increase in risk might be because of the adverse effect of severe immunosuppression in the past. However, the highest CD4+ levels possible should be maintained in the present. 


OBJECTIVE: Nearly half of individuals living with HIV in the USA are now 50 or older. This rapidly ageing populace may be at an increasingly greater risk of Alzheimer's disease. However, the potential interaction between HIV-disease and Alzheimer's disease pathogenesis (i.e. Alzheimer's disease genetic risk factors) on brain function remains an open question. The present study aimed to investigate the impact of APOE epsilon4 on brain function in middle-aged to older people with HIV (PWH), as well as the putative interaction between epsilon4 and HIV disease severity.

METHODS: Ninety-nine PWH participated in a cross-sectional study (56.3 +/- 6.5 years, range 41-70 years, 27 women, 26 epsilon4 carriers and 73 noncarriers). Structural MRI and resting-state functional MRI were collected to assess alterations in brain structure and functional connectivity, respectively.

RESULTS: APOE epsilon4 was associated with worse memory performance and reduced functional connectivity in the memory network. The functional connectivity reduction was centred at the caudate nucleus rather than hippocampus and correlated with worse memory performance. In epsilon4 carriers, low CD4+ cell count nadir was associated with reduced functional connectivity in the memory network, but this association was absent in noncarriers. Furthermore, there was an indirect detrimental impact of epsilon4 on memory performance through memory network functional connectivity. However, this indirect effect was contingent on CD4+ cell count nadir, that is the indirect effect of epsilon4 on memory was only significant when CD4+ cell count nadir was low.

INTERPRETATION: APOE epsilon4 is associated with reduced memory and reduced functional connectivity within the memory network, and low CD4+ cell count nadir -- indicating a history of severe immunosuppression -- may exacerbate the effects of epsilon4. 

Purpose of this Program: The AAHIVM, ACRIA and AGS (collectively, the “Sponsors,” “we” or “us”) are sponsors of this Website and through it seek to address the unique needs and challenges that older adults of diverse populations living with HIV face as they age. However, the information in this Website is not meant to supplant the advice provided in a doctor-patient relationship.

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