Sage Journals: Discover world-class research

Abstract

HIV-associated neurocognitive disorders (HANDs) are common, often go undetected, and can impact treatment outcomes. There is limited evidence on how to perform routine cognitive screening in HIV clinical settings. To address this, 44 HIV-positive males were recruited from a Veteran Affairs Infectious Disease clinic and completed the Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS), and Depression Anxiety and Stress Scale-21. In all, 50% scored below the MoCA cutoff and 36% scored below the IHDS cutoff. Current CD4 was the strongest predictor of an abnormal MoCA score (P = .007, 95% confidence interval [CI]: 0.987-0.998) and elevated depression was the second strongest predictor (P = .008, CI: 1.043-1.326). Combination antiviral therapy use and age were not significant predictors in this model. The MoCA appeared to be a reasonable screening tool to detect cognitive impairment in HIV-positive patients, and although it is not sufficient to diagnose HAND, it has the potential to provide meaningful clinical data.

Keywords

HIV/AIDS HAND cognitive impairment veterans depression

Introduction

HIV-associated neurocognitive disorders (HANDs) are common. Even in the era of effective combination antiviral therapy (cART), 30% to 50% of HIV-positive patients have been found to have some degree of mild–moderate cognitive impairment that is often undetected and can interfere with treatment adherence and other health outcomes.^1

–5 Further complicating this issue, many people living with HIV are aging. In 2011, there were over 25 000 HIV-positive veterans receiving care, 66% of whom were between the ages of 50 and 69.⁶ There are many other comorbid factors that can contribute to cognitive impairment in this population, including hepatitis C coinfection, substance use (particularly methamphetamine abuse), depression, and anxiety.^7

–10

Using the Frascati criteria, HAND is defined as 1 of the 3 conditions: asymptomatic neurocognitive impairment in which neuropsychological test performance is at least 1 standard deviation (SD) below normative data in at least 2 domains with intact daily functioning; mild neurocognitive disorder is characterized by similar neuropsychological testing impairment, with impaired daily functioning; and HIV-associated dementia is characterized by severe deficits in at least 2 cognitive domains (typically ≥2 SDs below normative data) and more severe daily functioning impairment. Given the implications, screening is recommended to identify patients experiencing HAND.^2,11 Routine screening could elucidate functional impairment in patients and arm clinicians with the necessary knowledge to manage their patients’ limitations. However, there is insufficient evidence to guide when and how to screen.^12,13 Although brief batteries have been proposed and certain tests highlighted,^2,3,12,14,15 there remains a need for brief screeners that are sensitive, easily accessible, and can be administered by clinical staff across a range of disciplines and settings.

The Montreal Cognitive Assessment (MoCA) is a brief screening measure that has been shown to have high sensitivity and specificity in detecting mild cognitive impairment (MCI), with a 90% sensitivity rate for detection in an elderly population, compared to 18% detection of MCI with the Mini-Mental Status Examination (MMSE).¹⁶ The MoCA and MMSE yield a maximum score of 30, with scores of ≥26 and ≥24, respectively, suggestive of normal cognition.^16,17 Among HIV-positive patients older than age 60, the MoCA identified patients with HAND at a sensitivity of 72% and specificity of 67%, using a cutoff of 25, suggestive of moderate performance characteristics.¹² In contrast, 74% of those with HAND obtained an MMSE score of ≥28 and paralleling earlier findings, the authors concluded that the MMSE is not a sensitive tool for detecting HAND.^12,18
–20 The authors recommended additional screening tools be employed to improve the use of the MoCA.¹² In a Korean sample with a mean age of 45.12, the MoCA had a specificity of 73% and sensitivity of 53% using a cutoff of ≤25 and using a cutoff of ≤10, the International HIV Dementia Scale (IHDS) had a specificity of 61% and sensitivity of 73%.²¹ The MoCA has been validated for use with older adults and compared to neuropsychological batteries.^22,23 Valcour³ reviewed existing literature on screening for cognitive impairment in HIV-positive patients and suggested that the MoCA shows promise but as of yet has insufficient data to support its use without additional measures. Koski et al²⁴ also found the MoCA was an adequately sensitive measure to assess cognitive impairment in HIV among a wide range of adults (mean age of 47.3), although it had reduced precision in detecting subtle declines in higher functioning individuals.

To address these gaps in the literature, the objectives of this pilot study were to (1) determine the proportion of patients who screened below the cutoff on the MoCA and the IHDS and (2) examine the relationship between performance on the MoCA, IHDS, and factors that might predict poor performance such as demographics, current and historical substance use, current viral load (VL) and CD4 count, CD4 nadir, current medication regimen, and mood (depression, anxiety, and stress).

Methods

Forty-four male, HIV-positive veterans, aged 40 or older, were recruited from an Infectious Disease clinic in an urban, VA Medical Center. Participants provided written, informed consent, and completed demographic questionnaires and measures evaluating substance use, mood symptoms, and cognitive impairment. The battery consisted of the MoCA¹⁶; the IHDS, which has been validated for detection of HAND in an HIV-positive population²⁵; and the Depression Anxiety and Stress Scale-21 (DASS-21), a 21-item measure with subscales for depression, anxiety, and stress that demonstrates good reliability and validity.²⁶ Patients with active psychosis, acute intoxication at the time of consent, organic brain syndrome (HAND, alcoholic or hepatic encephalopathy, or multi-infarct dementia; as determined by an existing medical diagnosis), or previous neuropsychological testing within the past 2 years were excluded from the study. Participants were included in the study if their most recent laboratory results (HIV serology, CD4, plasma HIV VL, and CD4 nadir) were available by self-report and/or chart verification. A total of 118 patients were referred for this study and 39 declined to participate. In all, 5 were excluded due to recent neuropsychological testing and 2 were excluded due to a diagnosis of dementia. A total of 47 patients consented to participate and 3 were excluded from analysis due to incomplete screening data. If during the study participants scored below the accepted cutoff on the MoCA (26) and/or IHDS (10), they were referred for further evaluation and appropriate treatment. All analyses were conducted using SPSS 22.0. This study was approved by the Human Subjects Committee at the University of California, San Francisco.

Results

The mean age of this sample was 58.8 (SD 8.43) and 61.4% were caucasian, 20.5% were black, and 13.6% were hispanic (Table 1). Participants had a mean of 17.9 (SD 8.3) years since their HIV diagnosis and 93.2% were taking cART. Fifty-nine percent of patients had a history of a psychiatric disorder. There were no significant differences in age, education, income, psychiatric diagnosis, HIV clinical variables, and hepatitis C virus (HCV) coinfection between participants who scored above the MoCA cutoff from those who scored below (Table 1). The MoCA score had a strong Spearman rank correlation with the IHDS of 0.69.

Table 1.

Demographics by MoCA Score.

Variable	All, N = 44	MoCA <26, n = 22	MoCA >26, n = 22	Statistics
Age, mean (median)	58.84 (59.00)	58.14 (60.50)	59.55 (59.00)	t = −0.556 (42), P = .58
CD4, mean (SD)	490.64 (228.34)	392.9 (171.56)	588.36 (239.40)	t = 3.11 (42), P = .003
CD4 Nadir, mean (SD)	269.25 (217.61)	304.23 (246.60)	234.27 (183.28)	z = −0.881, P = .379
Years with HIV, mean (SD)	17.9 (8.3)	18.3 (9.0)	17.5 (7.7)	t = −0.3047 (42), P = .76
On cART	41 (93.2%)	20 (45%)	21 (48%)	χ² (1, N = 44) = 0.00, P = 1.00
HIV viral load undetectable	38 (86.3%)	18 (40.9%)	20 (45.5%)	χ² (1, N = 44) = 0.77, P = .380
HCV+	17 (38.6%)	8 (18%)	9 (20%)	χ² (1, N = 44) = 0.00, P = 1.00
Psych diagnosis	26 (59.1%)	15 (34%)	11 (25%)	χ² (1, N = 44) = 1.50, P = .22
Race: African American	9 (20.5%)	8 (18)	1 (2%)
Race: Caucasian	27 (61.4%)	11 (25%)	16 (36%)
Race: Hispanic	6 (13.6%)	2 (5%)	4 (9%)
Race: other	2 (4.5%)	1 (2%)	1 (2%)	Fisher = 0.05
Education, mean (SD)	14.63 (2.39)	14.3 (2.52)	14.9 (2.29)	t = 0.7522 (42), P = .456
Annual income, mean (median)	39 867 (26 500)	40 074 (17 600)	39 722 (40 000)	z = 1.123, P = .262

Abbreviations: cART, combination antiviral therapy; HCV+, hepatitis C virus seropositive; MoCA, Montreal Cognitive Assessment; SD, standard deviation; χ², chi-square.

Direct logistic regression was conducted to evaluate the impact of CD4, age, use of cART, and depression on the likelihood of receiving a score below the cutoff on the MoCA. These variables were selected as important factors that can influence neurocognitive outcomes in HIV. Due to our sample size, the regression model was limited to inclusion of 4 variables. The overall model was statistically significant, χ² (4, N = 44) = 23.020, P < .0005, indicating that it was able to distinguish MoCA scores above (≥26) and below (< 26) the cutoff (Table 2). This 4-factor model explained between 40.7% (Cox and Snell R ²) and 54.3% (Nagelkerke R ²) of the variance in MoCA score and correctly classified 77.3% of the cases.

Table 2.

Results by MoCA Score.

Variable	All, N = 44	MoCA <26, n = 22	MoCA >26, n = 22	Statistics
MoCA, mean (SD)	25.24 (2.85)	23.18 (2.46)	27.31 (1.25)	P = .000
IHDS, mean (SD)	10.53 (1.52)	9.68 (1.56)	11.39 (0.89)	Fisher = 0.004
DASS-D, mean (SD)	8.5 (9.70)	12.27 (11.50)	4.72 (5.54)	P = .0374
DASS-A, mean (SD)	6.4 (8.0)	8.27 (9.49)	4.55 (5.7)	P = .410
DASS-S, mean (SD)	12.1 (10.0)	15.45 (11.06)	8.73 (7.57)	P = .04

Abbreviations: DASS-A, Depression Anxiety and Stress Scale-Anxiety; DASS-D, Depression Anxiety and Stress Scale-Depression; DASS-S, Depression Anxiety and Stress Scale-Stress; IHDS, International HIV Dementia Scale; MoCA, Montreal Cognitive Assessment; SD, standard deviation.

As shown in Table 3, current CD4 and depression made a unique, statistically significant contribution to the model. The strongest predictor of a lower MoCA score was current CD4 count (odds ratio [OR] = 0.992; P = .007, 95% confidence interval [CI]: 0.987-0.998), even after controlling for age, cART, race/ethnicity, and depression score. The second strongest predictor of a lower MoCA was the DASS-21 depression score (OR = 1.176; P = .008, CI: 1.043-1.326), after controlling for current CD4, age, and cART. Age, race/ethnicity, and cART use were not significant predictors in this model.

Table 3.

Logistic Regression of the Likelihood of a MoCA Score <26.

Variable	B	SE	Wald	P	95% CI for Exp(B)

					Exp(B)	Lower	Upper
Age	0.055	0.54	1.050	.306	1.057	0.951	1.175
cART	−2.993	1.851	2.614	.106	0.050	0.001	1.888
DASS-D	0.162	0.061	6.996	.008	1.176	1.043	1.326
CD4	−0.008	0.003	7.303	.007	0.992	0.987	0.998
Constant	2.007	3.366	0.356	.551	7.440

Abbreviations: cART, antiretrovirol; CI, confidence interval; DASS-D, Depression Anxiety and Stress Scale-Depression; MoCA, Montreal Cognitive Assessment; SE, standard error.

Discussion

The primary goals of this study were to (1) determine the proportion of treatment-seeking, HIV-positive patients older than the age of 40 who screened below the MoCA and IHDS cutoffs for impairment and (2) examine the predictive factors that differentiated those patients who scored below the cutoff on the MoCA from those who scored in the nonimpaired range. Of the 44 patients, 50% (22) scored below the cutoff of 26 on the MoCA and 36% (16) scored below the IHDS cutoff of 10. Our statistical model was able to distinguish between these groups and accurately predicted performance in 77.3% of cases. Current CD4 count and DASS-21 depression score significantly differentiated between these groups.

Nearly half of the participants scored below the standard cutoff of the MoCA and over a third scored below the standard cutoff on the IHDS, which mirrors results from other studies^1,2 and points to the high burden of impairment in this patient population. Considering current CD4 count and depression may prove useful in determining who may benefit from additional cognitive screening and further assessment of psychiatric concerns.

There is current discussion in the field about HAND diagnostic criteria, effective assessment strategies, treatment implications, and the role of screening for cognitive impairment.^{1,2,9,11,27,28} Given the lack of a gold standard, high rates of false positives, and the broad definition of cognitive impairment,²⁹ the risks of screening must be balanced with the clinical benefit. Another consideration for the implementation of screening is the availability of follow-up, which for mild or moderate levels of impairment should include providing cognitive rehabilitation services and appropriate medical and mental health follow-up, as indicated. Further examination of appropriate screening measures for reliably detecting HAND is imperative.

This study had several limitations. Given the small sample size, we were underpowered to detect certain potential and known correlates of cognitive impairment, such as CD4 nadir, cART adherence, and the impact of hepatitis C coinfection (see Table 1). However, CD4 nadir and HCV coinfection did not significantly differ between those who scored above or below the MoCA cutoff.

Although the presence of a psychiatric disorder did not significantly differentiate those who scored above or below the MoCA cutoff, low scorers had significantly higher depression and stress scores. This may have negatively impacted their performance on the battery, contributing to a lower score, as depression in elders is related to executive functioning deficits, even after the depressive symptoms have abated.^30,31 Although we obtained data on psychiatric history, specific diagnoses were unavailable. Very few of the patients who screened below the MoCA and IHDS cutoffs agreed to further neuropsychological testing; thus we were unable to determine the rate of false positivity. To obtain the most representative data of our clinic population and HIV clinics across the VA and allow comparison to the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study,¹ we set the lower age limit to 40 years.

Despite these limitations, the MoCA appears to be a reasonable screening tool for HIV-positive patients; however, its utility is heightened by the addition of other cognitive and psychiatric measures. The MoCA is feasible for use by nonphysician providers and paraprofessionals and is available in the public domain. It would be beneficial for future studies to compare multiple brief screening tools to a full neuropsychological test battery to optimize a screening tool that can reliably detect HAND and discriminate between HAND and normal cognition.

Footnotes

Acknowledgments

The authors wish to express their appreciation to the research participants and colleagues at the SF VAMC ID clinic for their support and cooperation.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Department of Veterans Affairs (5101BX001048) and NIH (R01 NS051132) for research funding.

References

Heaton

Clifford

Franklin

. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology. 2010;75 (23):2087–2096.

Mind Exchange Working Group. Assessment, diagnosis, and treatment of Human Immunodeficiency Virus-Associated neurocognitive disorders: a consensus report of the mind exchange program. Clin Infect Dis. 2013;56 (7):1004–1017. doi: 10.1093/cid/cis975.

Valcour

. Evaluating cognitive impairment in the clinical setting: practical screening and assessment tools. Top Antivir Med. 2011;19(5):175–180.

Panos

Del Re

Thames

. The impact of neurobehavioral features on medication adherence in HIV: evidence from longitudinal models. AIDS Care. 2014;26(1):79–86.

Thames

Arentoft

Rivera-Mindt

Hinkin

. Functional disability in medication management and driving among individuals with HIV: a 1-year follow-up study. J Clin Exp Neuropsychol. 2013;35 (1):49–58.

The State of Care for Veterans with HIV/AIDS: 2011 Summary Report. http://www.hiv.va.gov/provider/policy/2011-HIV-summary-report.asp. Published June 13, 2012. Accessed July 15, 2014.

Chana

Everall

Crews

. Cognitive deficits and degeneration of interneurons in HIV+ methamphetamine users. Neurology. 2006;67 (8):1486–1489.

Hilsabeck

Castellon

Hinkin

. Neuropsychological aspects of co-infection with HIV and hepatitis C virus. Clin Infect Dis. 2005;41 (suppl 1):38–44.

Hilsabeck

Huckans

. Human immunodeficiency virus and hepatitis. In: Bush

, ed. Neuropsychological Practice With Veterans. New York, NY: Springer; 2012:201–226.

10.

Sun

Abadjian

Rempel

Monto

Pulliam

. Differential cognitive impairment in HCV coinfected men with controlled HIV compared to HCV monoinfection. J Acquir Immune Defic Syndr. 2013;62 (2):190–196.

11.

Griffin

Gerhardstein

. Cognitive testing in HIV/AIDS: a case for early assessment. HIV Clin. 2010;22 (4):6–9.

12.

Milanini

Wendelken

Esmaeili-Firidouni

Chartier

Crouch

Valcour

. The Montreal Cognitive Assessment to screen for cognitive impairment in HIV patients older than 60 years. J Acquir Immune Defic Syndr. 2014;67 (1):67–70.

13.

Pozniak

Rackstraw

Deayton

. HIV-associated neurocognitive disease: case studies and suggestions for diagnosis and management in different patient sub-groups. Antivir Ther. 2013;19(1):1–13.

14.

Cysique

Murray

Dunbar

Jeyakumar

Brew

. A screening algorithm for HIV-associated neurocognitive disorders. HIV Med. 2010;11 (10):642–649.

15.

Moore

Roediger

Eberly

. Identification of an abbreviated test battery for detection of HIV-associated neurocognitive impairment in an early-managed HIV-infected cohort. PLoS One. 2012;(7)11. doi:10.1371/journal.pone.0047310.

16.

Nasreddine

Phillips

Bédirian

. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53 (4):695–699.

17.

Lezak

Howieson

Loring

. Neuropsychological Assessment. 4th ed. New York, NY: Oxford University Press; 2004.

18.

Ganasen

Fincham

Smit

Seedat

Stein

. Utility of the HIV dementia scale (HDS) in identifying HIV dementia in a south African sample. J Neurol Sci. 2008;269 (1-2):62–64.

19.

Skinner

Adewale

DeBlock

Gill

Power

. Neurocognitive screening tools in HIV/AIDS: comparative performance among patients exposed to antiretroviral therapy. HIV Med. 2009;10 (4):246–252.

20.

Kamminga

Cystique

Batchelor

Brew

. Validity of cognitive screens for HIV-associated neurocognitive disorder: a systematic review and an informed screen selection guide. Curr HIV/AIDS Rep. 2013;10 (4):342–355.

21.

Lee

Ahn

. HIV-associated neurocognitive disorder in HIV-infected Koreans: the Korean NeuroAIDS Project. HIV Med. 2014;15 (8):470–477.

22.

Luis

Keegan

Mullan

. Cross validation of the Montreal Cognitive Assessment in community dwelling older adults residing in the Southeastern US. Int J Geriatr Psychiatry. 2009;24 (2):197–201.

23.

Lam

Harry

van Gaal

Black

. Validation of the Montreal Cognitive Assessment against detailed neuropsychological measures. Can J Geriatr. 2009;61 (12):138.

24.

Koski

Brouillette

Lalonde

. Computerized testing augments pencil-and-paper tasks in measuring HIV-associated mild cognitive impairment. HIV Med. 2011;12:472–480.

25.

Sacktor

Wong

Nakasujja

. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS. 2005;19 (13):1367–1374.

26.

Lovibond

. The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther. 1995;33 (3):335–343.

27.

Antinori

Arendt

Becker

. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69 (18):1789–1799.

28.

Schouten

Cinque

Gisslen

Reiss

Portegies

. HIV-1 infection and cognitive impairment in the cART era: a review. AIDS. 2011;25:561–575.

29.

Gisslén

Price

Nilsson

. The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence? BMC Infect Dis. 2011;11:356.

30.

Alexopoulos

Meyers

Young

Kakuma

Silbersweig

Charlson

. Clinically defined vascular depression. Am J Psychiatry. 1997;154 (4):562–565.

31.

Murphy

Alexopoulos

. Longitudinal association of initiation/perseveration and severity of geriatric depression. Am J Geriatr Psychiatry. 2004;12 (1):50–56.