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Diagnosis and Treatment of Cognitive Impairment in HIV Patients
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https://www.ajmc.com/newsroom/diagnosis-and-treatment-of-cognitive-impairment-in-hiv-patients
Wallace Stephens
Published on: February 18, 2019
As survival rates for people living with HIV continue to increase and the population grows older, cognitive impairment is becoming more common.
Prevalence of cognitive impairment (CI) has increased among the HIV population while services for diagnosing and treating afflicted individuals remains scarce, according to a new study, which explored the development and management of neurological disorders in 52 patients living with HIV (PLWH).
A UK-based clinic performed a memory assessment service and found that 79% of patients had impartial CI: 31% met conditions for HIV-associated neurocognitive disorder (HAND), 4% were diagnosed with dementia, 27% showed CI related to mental illness or substance abuse, 13% had CI believed to be caused by factors other than HIV, and 4% had CI due to unknown reasons. The researchers found 62% of patients displayed at least partial abnormality on magnetic resonance imaging brain scans and that all patients scored significantly below average on tests of global cognition and executive functioning. The authors advocated that specialist HIV memory services should be included in future patient care.
HAND serves as an umbrella term to cover a wide spectrum of neurological disorders, including asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. The prevalence of HAND has been frequently determined by the Frascati criteria, a neurocognitive rating scale developed in 2007 that involves neuropsychological testing across multiple cognitive domains. However, the Frascati criteria has been criticized to lack specificity and sensitivity, resulting in an uncommon amount of false-positive diagnoses.
"Based on Frascati criteria, 81% of patients attending the clinic would be diagnosed with HAND," the authors explained. "Using our diagnostic processes, we found 79% had objective CI, however of these, 61% had a reason for this that was not HIV-related and only 39% had 'true' HAND."
The clinic's team consisted of a physician specializing in HIV, a geriatric psychiatrist skilled in dementia diagnosis and treatment, a neuropsychologist with an assistant, a clinical psychologist, a nurse clinically skilled in HIV treatment, and virtual support provided by neurology and neuroimaging services. The clinic conducted 2 monthly sessions with an additional monthly follow-up. The goal of the clinic was to diagnose CI in patients and establish a treatment and management plan. PLWH who had unexplained cognitive disorders or mentioned cognitive complaints were referred to the clinic.
Convincing evidence suggests a strong and complex relationship between mental illness, CI, and HIV. Overall, 27% of patients were determined to have a mental health condition, derived from either sleeplessness, obsessive compulsive disorder, or substance abuse, which was inferred to be responsible for their CI. HIV diagnosis can cause patients to develop depression and anxiety due to psychological distress and social stigmas associated with the condition. It was also significant that 44% of patients were taking antidepressant medication.
"In our clinic it has been vital to be able to address the mental health issues of patients," the authors wrote. "This has involved either referrals to HIV-specialist mental health services or to general mental health services."
CI has reportedly become more common in PLWH and is predicted to become a growing issue as survival rates rise and the population grows older. Mild to moderate CI has increasingly been reported and is associated with nonadherence to medication, higher likelihood of unemployment, shorter life expectancy, and lower overall quality of life.
Following the study, 23 of the original 52 patients were discharged—9 were found to have no objective CI, 8 had CI due to mental health issues, 1 had CI due to previous HIV-related encephalitis, 1 had CI due to a previous traumatic brain injury, 3 were diagnosed with mild HAND, and 1 patient with Alzheimer's disease died.
"Our experience suggests that the need exists for specialist HIV memory services and that such a model of working can be successfully implemented into HIV patient care," the authors concluded. "Further work is needed on referral criteria and pathways. Diagnostic processes and treatment offered needs to consider and address the multifactorial etiology of CI in HIV and this is essential for effective assessment and management."
Reference
Alford K, Banerjee S, Nixon, E, et al. Assessment and management of HIV-associated cognitive impairment: experience from a multidisciplinary memory service for people living with HIV. Brain Sci. 2019;9(2):37. doi: 10.3390/brainsci9020037.
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Assessment and Management of HIV-Associated Cognitive Impairment: Experience from a Multidisciplinary Memory Service for People Living with HIV
Brain Sci. Feb 8 2019
Our clinic patients diagnosed with HAND (based on our diagnostic criteria) showed impairments in tests of immediate and delayed memory, with mild impairments in attention, visuospatial skills and language—demonstrating a more subtle subcortical involvement and cortical involvement possibly influenced by age [33].
Our data show how important it is to have the skills available to assess mental health and clear pathways for those attending HIV services who have problems with CI. The relationship between HIV, mental illness, and CI is complex.
Interventions addressing cardiovascular risk factors and mental wellbeing appear to be of value [42,44]. At the clinic we offer patients informal advice on lifestyle (e.g., diet, exercise, sleep hygiene, drugs/alcohol intake), mental health management, adherence to cART and cognitive strategies, along with recommendations to their GP on the control of CVD risk factors.
Early (and efficient) detection of milder forms of HAND (i.e., ANI) is a priority, with the British HIV Association (BHIVA) recommending all PLWH should be screened annually for CI.
Based on Frascati criteria, 81% of patients attending the clinic would be diagnosed with HAND. Using our diagnostic processes, we found 79% had an objective CI, however of these, 61% had a reason for this that was not HIV-related and only 39% had 'true' HAND.
The finding that our clinic population has a much lower quality of life than that of people attending memory services is of interest. This suggests that these concerns about CI in the context of HIV, and with high comorbidity with mental disorders, act to decrease the quality of life of those with HIV and CI.
This high prevalence of CI detected is in line with the purpose of the clinic, and the heterogeneity of causation of CI in HIV is well illustrated.
It is significant that 27% of those who attended the clinic had a mental health condition which was likely to be responsible for their subjective and objective CI. A number of other patients attending the clinic were also experiencing poor mental health which was not thought to be causing their CI. It is also striking that 44% of patients were taking antidepressant medication. Current management of depression in HIV relies primarily on antidepressant medication [34] with open-label trials of different antidepressants, across HIV illness stage, showing response rates of 70-90% (equivalent to non-HIV infected populations) and good levels of tolerance [35,36,37]. A recent systematic review examining the efficacy of different interventions for PLWH experiencing depression, found that psychotropic and HIV-specific psychological interventions incorporating a cognitive behavioural component were most effective [38]. In our clinic it has been vital to be able to address the mental health issues of patients. This has involved either referrals to HIV specialist mental health services (if mental health issues are related to HIV issues such as diagnosis) (n = 8) or to general mental health services (n = 16).
The psychological and social impact of an HIV diagnosis (stigma, discrimination and isolation) can contribute to symptoms of depression and anxiety, and therefore to subjective and objective CI. In addition, HIV replication in the Central nervous system (CNS) causes depression via the modification of brain structures [39], somatostatin dysregulation [40] and increased inflammatory cytokines [41], as well as lowering cognitive reserve and impairing cognitive function directly and via co-infection. Added into this are lifestyle factors such as drug and alcohol use which may be exacerbated by mental health issues and will have a negative impact on cognitive function.
Medication treatment strategies for CI have generally proved disappointing, within the clinic we modified cART regimens only due to patient complaint of side effects (and would have modified if presence of CSF HIV RNA was detected); besides this little recommendation or indeed clarity of evidence exists. Improvements in neurocognition using medications with better CNS penetration or maraviroc is widely debated [45,46,47] and while evidence points to neurotoxicity associated with some regimens (i.e., Efavirenz), clarity around the most efficacious cART regimen to use with patients living with HAND is unclear.
Conclusions
In the UK, 48% of those accessing HIV services are now aged 45 and over, with large increases seen in those of an older age in the past decade. Recent modelling work predicts that by 2030 73% of PLWH will be over 50 years of age [52]. Multidisciplinary working is vital to the successful management of such patients where complex multimorbidity is likely to be the norm. This service evaluation provides tentative evidence that the need exists, that the model of care we have developed is feasible and that there may be value in establishing similar models of working in HIV care for those with impairment in cognitive function.
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Assessment and Management of HIV-Associated Cognitive Impairment: Experience from a Multidisciplinary Memory Service for People Living with HIV
Kate Alford 1 , Sube Banerjee 2,3 , Eileen Nixon 4 , Clara O'Brien 4 , Olivia Pounds 4 ,
Andrew Butler 5 , Claire Elphick 3 , Phillip Henshaw 3 , Stuart Anderson 4 and Jaime H. Vera 1,4,5, *
1 Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton BN1 9PX, UK;
K.Alford@bsms.ac.uk
2 Centre for Dementia Studies, Brighton and Sussex Medical School, Brighton BN1 9PX, UK;
S.Banerjee@bsms.ac.uk
3 Sussex Partnership NHS Foundation Trust, Worthing BN13 3EP, UK;
Claire.Elphick@sussexpartnership.nhs.uk (C.E.); Phillip.henshaw@sussexpartnership.nhs.uk (P.H.)
4 Brighton and Sussex University Hospitals NHS Trust, Brighton BN2 1ES, UK;
E.Nixon@bsuh.nhs.uk (E.N.);
Clara.OBrien@bsuh.nhs.uk (C.O.); Olivia.Pounds@bsuh.nhs.uk (O.P.);
Stuart.Anderson@bsuh.nhs.uk (S.A.)
5 Department of Medicine, Brighton and Sussex Medical School, Brighton BN1 9PX, UK;
Andrew.Butler@bsms.ac.uk
* Correspondence: J.Vera@bsms.ac.uk; Tel.: +44-1273-523087
Abstract
As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients (avg age: 55) seen by the clinic. We present patient demographic data, assessment outcomes, diagnoses given and interventions delivered to those seen in the clinic.
• 41 patients (79%) of those seen in the clinic had objective CI:
• 16 (31%) met criteria for HIV-associated Neurocognitive Disorder (HAND),
• 2 (4%) were diagnosed with dementia,
• 14 (27%) showed CI associated with mental illness and/or drugs/alcohol,
• 7 (13%) had CI which was attributed to factors other than HIV and in
• 2 (4%) patients the cause remains unclear.
• 32 (62%) patients showed some abnormality on Magnetic Resonance Imaging (MRI) brain scans.
In 14 (27%) the CI was assessed as being secondary to mental health difficulties (depression, anxiety, OCD, poor sleep) and/or drug/alcohol abuse, 7 (14%) had CI which was attributable to factors other than HIV (2 prior Traumatic Brain Injury (TBI), 4 cerebrovascular diseases and 1 cortical dysplasia), and in 2 (4%) cases the CI cause remains unclear (both are recent cases and we are awaiting LP/MRI or other investigations).
mean DEMQOL total score was 70 (17.1). We found no correlation between EQ-5D-5L score and DEMQOL total score and no correlation between any of the HIV data variables and either DEMQOL total score or ED-5Q-5L score. The scores on DEMQOL are indicative of a lower quality of life than in the population of those attending memory assessment services where the mean DEMQOL score at assessment of 197 attenders was 89.6 (14.1); t (247) = 8.47, p < 0.0001 [31].
All but one patient had a new (n = 28) or recent MRI (n = 23) and 32 (62%) had some type of MRI brain abnormality. White matter (WM) hyperintensities were the most common finding (n = 22), of these 11 were considered vascular and indicative of cerebrovascular issues (i.e., ischaemia or small vessel disease). 8 scans showed evidence of cortical atrophy and 6 of subcortical atrophy. 4 patients demonstrated abnormalities consistent with HIV-associated CI (e.g., damage from previous HIV-associated encephalitis or leukoencephalopathy). 5 patients' scans had 'other' abnormalities, including meningioma, pontine lesions, left insular lesions, hyperintensities of the pons and siderosis.
One-sample t-tests suggest that scores on Total RBANS score were significantly worse in patients attending our clinic (80 ± 17.32) than normative scores (100 ± 15), t (51) = -8.31, p < 0.001. Indeed, our clinical cohort performed on average significantly worse than normative scores across all RBANS subdomains; Immediate memory (82.19 ± 20.75), t (51) = -6.19, p < 0.001; Visuospatial (94.54 ± 18.85), t (51) = -2.09, p = 0.04; Language (86.46 ± 15.46), t (51) = -6.31, p < 0.001; Attention (79.87 ± 16.9), t (51) = -8.59, p < 0.001; Delayed memory (79.21 ± 21.55), t (51) = -6.96, p < 0.001). Patients also completed a range of executive functioning tests. One-sample t-tests again revealed those attending the clinic performed significantly worse than normative scores (100 ± 15) in all executive functioning tests: NAB screening module mazes (89.63 ± 18.66), t (50) = -3.97, p < 0.001; DKEFS colour word interference test (83.79 ± 18.72), t (41) = -5.61, p < 0.001; Trails Test A (81.40 ± 20.14), t (49) = -6.53, p < 0.001; Trails Test B (74.37 ± 23.07), t (42) = -7.29, p < 0.001.
Patients attending the clinic performed significantly worse than normative scores on all tests of global cognition and executive function. Interventions offered to patients included combination antiretroviral therapy modification, signposting to other services, case management, further health investigations and in-clinic advice. Our experience suggests that the need exists for specialist HIV memory services and that such a model of working can be successfully implemented into HIV patient care. Further work is needed on referral criteria and pathways. Diagnostic processes and treatment offered needs to consider and address the multifactorial aetiology of CI in HIV and this is essential for effective assessment and management.
Results
From June 2016 to May 2018 the Orange Clinic assessed 52 patients. Demographic, HIV and health data of patients attending the clinic are presented in Table 2.
Of the 52 patients seen, 42 had HAND based on Frascati criteria. Using our diagnostic criteria, we found 11 (21%) patients to have no objective CI, 16 (31%) were diagnosed with HAND, 2 (4%) were diagnosed with dementia (one AD, 1 unspecified). In 14 (27%) the CI was assessed as being secondary to mental health difficulties (depression, anxiety, OCD, poor sleep) and/or drug/alcohol abuse, 7 (14%) had CI which was attributable to factors other than HIV (2 prior Traumatic Brain Injury (TBI), 4 cerebrovascular diseases and 1 cortical dysplasia), and in 2 (4%) cases the CI cause remains unclear (both are recent cases and we are awaiting LP/MRI or other investigations).
All but one patient had a new (n = 28) or recent MRI (n = 23) and 32 (62%) had some type of MRI brain abnormality. White matter (WM) hyperintensities were the most common finding (n = 22), of these 11 were considered vascular and indicative of cerebrovascular issues (i.e., ischaemia or small vessel disease). 8 scans showed evidence of cortical atrophy and 6 of subcortical atrophy. 4 patients demonstrated abnormalities consistent with HIV-associated CI (e.g., damage from previous HIV-associated encephalitis or leukoencephalopathy). 5 patients' scans had 'other' abnormalities, including meningioma, pontine lesions, left insular lesions, hyperintensities of the pons and siderosis.
Lumbar Punctures (LPs) were requested for 26 patients attending the clinic. Patients did not receive a LP when it was considered unnecessary (e.g., likely mental health causation for CI) or when patients refused it. Within our cohort there was no recorded cases of CSF escape.
The majority of patients were assessed using the Montreal Cognitive Assessment (MoCA) [12] prior to clinic attendance and the mean score was 23.6 (2.6). All other neuropsychological test scores were converted into Standard Scores (SS) to allow comparison of data (Mean = 100, SD = 15). Test of premorbid functioning (TOPF) clinic mean was 99.2 (11.8) and Reynolds Intellectual Screening Test (RIST) clinic mean was 99.1 [15], indicating that the general intelligence of our sample was similar to the population mean. Mean performance on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale was 80 (17.3) and on each RBANS domain: immediate memory, 82.2 (20.8); visuospatial, 94.5 (18.9); language, 86.5 (15.5); attention, 79.9 (16.9); delayed memory, 79.2 (21.5). Figure 1 shows the mean RBANS scores seen in those attending the clinic against average scores reported in the literature from patients with Alzheimer's dementia and mild cognitive impairment [29,30]. Interestingly, women (n = 11) attending the clinic were outperformed by males on all measures, with statistically significant differences on measures of premorbid functioning (males in our cohort had higher premorbid IQ) (p < 0.01) as well as the mazes task (p = 0.02), visuospatial (p < 0.01), language (p = 0.001) and attention (p = 0.02) indices of the RBANS and the RBANS overall score (p = 0.01). Differences seen are likely due to differences in premorbid IQ, and that women attending the clinic tended to be from different cultural (i.e., where English is not the first language) and socio-economic backgrounds to the men.
One-sample t-tests suggest that scores on Total RBANS score were significantly worse in patients attending our clinic (80 ± 17.32) than normative scores (100 ± 15), t (51) = -8.31, p < 0.001. Indeed, our clinical cohort performed on average significantly worse than normative scores across all RBANS subdomains; Immediate memory (82.19 ± 20.75), t (51) = -6.19, p < 0.001; Visuospatial (94.54 ± 18.85), t (51) = -2.09, p = 0.04; Language (86.46 ± 15.46), t (51) = -6.31, p < 0.001; Attention (79.87 ± 16.9), t (51) = -8.59, p < 0.001; Delayed memory (79.21 ± 21.55), t (51) = -6.96, p < 0.001). Patients also completed a range of executive functioning tests. One-sample t-tests again revealed those attending the clinic performed significantly worse than normative scores (100 ± 15) in all executive functioning tests: NAB screening module mazes (89.63 ± 18.66), t (50) = -3.97, p < 0.001; DKEFS colour word interference test (83.79 ± 18.72), t (41) = -5.61, p < 0.001; Trails Test A (81.40 ± 20.14), t (49) = -6.53, p < 0.001; Trails Test B (74.37 ± 23.07), t (42) = -7.29, p < 0.001.
Mental Health and Quality of Life Assessments
The mean score on total DASS21 across the patients attending the clinic was 27 (SD = 13.4), the mean depression score was 8 (52), the mean anxiety score was 8 (4.9) and the mean stress score 11.0 (5.3). Across the clinic the mean ED-5Q-5L score was 65 (23.9) and mean DEMQOL total score was 70 (17.1). We found no correlation between EQ-5D-5L score and DEMQOL total score and no correlation between any of the HIV data variables and either DEMQOL total score or ED-5Q-5L score. The scores on DEMQOL are indicative of a lower quality of life than in the population of those attending memory assessment services where the mean DEMQOL score at assessment of 197 attenders was 89.6 (14.1); t (247) = 8.47, p < 0.0001 [31].
Of the 52 patients who attended the clinic, 23 are now discharged. Of those discharged, 9 had no objective CI, 8 had CI due to mental health issues which were best served by other services, 1 patient had CI due to prior HIV encephalitis, 1 had CI due to a previous traumatic brain injury, and 3 had mild HAND. 10 of these patients were discharged following initial appointment. These patients were given in-clinic advice (n = 9), referred to mental health services (n = 3), referred to community drug support services (n = 1) and provided with a recommendation for strict control of cardiovascular risk factors (n = 1). The other 12 were discharged following satisfactory feedback from further investigations or once a management plan had been fully implemented and the one patient with Alzheimer's disease died.
29 patients are still open to the clinic. Of these 15 are due to have repeat cognitive testing to assess progression and/or impact of management plan and a further 8 are due to be followed-up following implementation of management plans (e.g., psychological therapy, in-clinic advice on lifestyle/mental health management e.g., sleep hygiene, medication changes, stricter control of CVD risk factors). 2 patients will be reviewed again following MRI/LP/other health assessment feedback before a management plan is devised. Finally, 4 patients remain open to the clinic but are not due to be seen unless needed, these patients are all either responding well to their current plan or have been referred to another health service.
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