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Factors Associated With Incident Human Immunodeficiency Virus–Dementia
Yaakov Stern, PhD;
Michael P. McDermott, PhD;
Steven Albert, PhD;
Donna Palumbo, PhD;
Ola A. Selnes, PhD;
Justin McArthur, MD;
Ned Sacktor, MD;
Giovanni Schifitto, MD;
Karl Kieburtz, MD, MPH;
Leon Epstein, MD;
Karen S. Marder, MD, MPH;
for the Dana Consortium on the Therapy of HIV–Dementia and Related
Cognitive Disorders
Arch Neurol. 2001;58:473-479.
ABSTRACT
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Background Antecedents to human immunodeficiency virus–dementia (HIV-D) are
poorly understood.
Objective To identify risk factors for HIV-D.
Methods Subjects who are positive for HIV who have CD4+ counts either
below 200/µL or below 300/µL with evidence of cognitive impairment
were enrolled in this study. Neurologic, cognitive, functional, and laboratory
assessments were done semiannually for up to 30 months. Human immunodeficiency
virus–dementia was diagnosed using American Academy of Neurology criteria
for probable HIV-1–associated dementia complex.
Results One hundred forty-six nondemented patients were enrolled, 45 of whom
subsequently met criteria for incident HIV-D. In univariate analyses using
the Cox proportional hazards regression model, the following variables were
significantly associated with time to develop dementia: cognitive: abnormal
scores on Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol tests;
attention-memory, psychomotor, and executive function domain scores; and the
diagnosis of minor cognitive/motor disorder; neurologic and medical: increased
abnormalities on the neurologic examination, extrapyramidal signs, history
of HIV-related medical symptoms; functional: higher reported role or physical
function difficulties. Depression was also a strong risk factor, along with
sex, hematocrit, hemoglobin, and ß2-microglobulin levels.
In a multivariate model that used cognitive domain scores, covariates with
significant hazard ratios included depression, executive dysfunction, and
the presence of minor cognitive/motor disorder.
Conclusion Cognitive deficits, minor cognitive/motor disorder, and depression may
be early manifestations of HIV-D.
INTRODUCTION
FEW STUDIES have examined the risk factors for dementia in patients
with human immunodeficiency virus (HIV) infection and these have focused primarily
on demographic and medical factors. Previous studies have suggested that older
age, history of HIV-related medical symptoms, lower hemoglobin levels, higher
plasma viral load,1 lower CD4+ cell
counts,2 and intravenous drug use3
are associated with a greater risk of developing dementia. There has been
some suggestion that zidovudine treatment is protective.4
While many studies have demonstrated subtle cognitive changes in patients
with HIV, and psychomotor slowing has been associated with an increased risk
of dementia,5 it is unclear whether these are
unrelated to later dementia or represent the early stages of a dementing process.
Similarly, diagnostic criteria have been proposed for HIV-associated minor
cognitive/motor disorder (MCMD), which applies to HIV-positive patients with
subtle cognitive, neurologic, and psychiatric symptoms but minimal functional
complaints.6 To our knowledge, the relationship
between this diagnosis and a later diagnosis of dementia has been unexplored.
This study prospectively followed up HIV-positive patients to evaluate which
clinical features noted at the initial visit were associated with an increased
risk of developing dementia. Potential correlates of incident dementia included
demographic, medical, neurologic, functional, and psychiatric features as
well as laboratory study results. In addition, all participants completed
a battery of neuropsychological tests, allowing us to assess the predictive
use of poor test performance and the presence of MCMD.
SUBJECTS AND METHODS
SAMPLE
The Dana Consortium on the Therapy of HIV–Dementia and Related
Cognitive Disorders was formed in 1994 to recruit a cohort of HIV-infected
individuals and examine risk factors for human immunodeficiency virus–dementia
(HIV-D). Subjects were recruited from infectious disease clinics or through
targeted advertising at 3 sites: Columbia University, New York, NY; Johns
Hopkins University, Baltimore, Md; and the University of Rochester, Rochester,
NY. Subjects were eligible for inclusion in the cohort if they were positive
for HIV, had subjective reports of memory or concentration problems, and had
CD4+ cell counts either below 200/µL or below 300/µL,
and cognitive impairment on neuropsychological testing (see "Neuropsychological
Testing" subsection). They were excluded from the cohort if they were not
ambulatory or if they had other neuropsychiatric conditions (eg, current or
past central nervous system infection, head injury, or schizophrenia) that
might cause cognitive impairment.
PROCEDURES
Assessments were performed semiannually for up to 30 months. At each
visit, subjects underwent a neurologic examination; completed a battery of
neuropsychological, functional, and psychiatric assessments; and had blood
drawn for laboratory studies. Data collected from all of these evaluations
were used to examine potential risk factors for incident HIV-D.
POTENTIAL CORRELATES OF INCIDENT HIV-D
Demographic Data
Age at initial visit, number of years of education, sex, race (white
vs other), use of antiretroviral therapy at the initial visit, consumption
of alcohol (at least weekly, less than weekly), and intravenous drug use during
the year prior to enrollment (all intravenous drug users in our study had
used drugs during that year) were used as independent variables.
Neurologic and Medical Examinations
A standardized history of HIV-related diagnoses was collected. The presence
of any one diagnosis (yes, no) was used as an independent variable in our
analyses. The neurologic examination was designed to capture signs associated
with HIV-D. The macroneurologic examination created for the AIDS (Acquired
Immunodeficiency Syndrome) Clinical Trials Group was used. The motor subscale
(Part III) of the Unified Parkinson Disease Rating Scale7
was administered to rate the presence or absence of extrapyramidal signs.
Total scores for the macroneurologic examination and the Unified Parkinson
Disease Rating Scale were dichotomized at or near their median values for
analysis.
Neuropsychological Testing
The neuropsychological battery was designed to delineate HIV-D and MCMD.
Where possible, tests recommended by the National Institute of Mental Health8 and the AIDS Clinical Trials Group were included.
The 8 tests included in the core neuropsychological battery covered
6 domains. Verbal memory was assessed with the Rey Auditory Verbal Learning
Test.9 Visual memory was assessed with the
Rey-Osterrieth Complex Figure 1
Delayed Recall Test.9 Constructional skills
were assessed with the Rey-Osterrieth Complex Figure 1 Immediate Recall Test. Psychomotor skills were measured
with the Digit Symbol Test.10 Motor skills
were assessed with the Grooved Pegboard (dominant and nondominant hand)11 and Timed Gait tests. Frontal systems were assessed
with Verbal Fluency12 and the Odd-Man-Out tests.13, 14
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Cumulative of incidence of human immunodeficiency virus–dementia
(HIV-D) in the study cohort (solid line). In addition to incidence in the
entire cohort, incidence in patients with (long dashed line) and without (short
dashed line) a diagnosis of minor cognitive/motor disorder at the initial
visit is shown.
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Performance for each test was referenced to age- and education-appropriate
norms. Norms for subjects with an educational level above high school were
those reported for the Multicenter AIDS Cohort Study, a cohort of homosexual
men15; norms for subjects with an education
at the high school level or below were those reported for the ALIVE (AIDS
Link to Intravenous Experience) cohort, a cohort of intravenous drug users.16 For the Odd-Man-Out Test, unpublished norms from
the homosexual men and intravenous drug user cohorts followed up at Columbia
University17, 18 were used.
At the initial visit, the presence of cognitive impairment sufficient
to meet study enrollment criteria was defined as performance 2 SDs below the
appropriate mean on 1 test, or 1 SD below the mean on 2 tests. If Timed Gait
performance was the only measure in which subjects scored 2 SDs below the
mean, subjects were not considered to have met criteria for cognitive impairment.
For statistical analysis, neuropsychological test scores were dichotomized
at 1 SD below the mean. For the Grooved Pegboard Test, a score greater than
1 SD below the appropriate norm for either the dominant or nondominant hand
was considered to be a deficit. For Timed Gait performance, 1.5 SDs below
the mean was used as the cutoff because of the nature of the available normative
data.
Composite scores were created from the neuropsychological test battery
with the aid of a principal component factor analysis using Varimax rotation.
Three factors were identified that accounted for 68.4% of the total variance:
attention-memory (Rey Auditory Verbal Learning Test—total score, trial
5 score, recall after interference, delayed recall, and correct recognition),
psychomotor speed (Grooved Pegboard, dominant and nondominant hands and Digit
Symbol Test), and executive function (Rey-Osterreith Complex Figure 1 Immediate Recall Test, Odd-Man-Out Test, and Verbal Fluency
Test). Composite scores for each of these factors were formed by first creating
a z score for each neuropsychological test variable
(using the Multicenter AIDS Cohort Study and ALIVE age- and education-based
norms) and then averaging the z scores across the
appropriate variables. These composite scores (average z scores) were dichotomized at 0 for statistical analysis.
We also used the presence of HIV-associated MCMD at the initial study
visit as an independent variable. Subjects received this diagnosis if they
had at least 2 deficits in cognitive tests (Digit Symbol Test, Rey Auditory
Verbal Learning Test) or neurologic examination (finger agility, alternating
movement, gait and coordination, limb coordination, emotional lability) and
a deficit in at least 1 role function. These are the same criteria used in
the diagnostic algorithm previously published based on American Academy of
Neurology guidelines,19 except in this study
we did not require the role function deficit to be attributed to a cognitive
source.
Functional Measures
Functional measures were chosen that would reflect the degree to which
cognitive deficits compromised everyday function. Measures were derived from
the Instrumental Activities of Daily Living (IADL) scales of Lawton and Brody,20 the Katz Instrumental Activities of Daily Living/Lawton
Personal Self-Maintenance Scale,21 and the
role functioning items of the Medical Outcomes Study.22
Two functional outcomes that reflect stress and stamina were also included:
the Karnofsky performance scale23 and the Medical
Outcomes Study physical function subscale.22
All scores were dichotomized at or near their median values for analysis except
for the Karnofsky performance scale, which was categorized as less than 80,
80 to 89, and 90 to 100. A score of less than 80 on this scale would suggest
the need for assistance with some Instrumental Activities of Daily Living
and an inability to work outside the home.
Psychiatric Assessment
The 20-item Center for Epidemiologic Studies–Depression Scale24 was used to assess mood. The Center for Epidemiologic
Studies–Depression Scale score was considered a continuous variable
in the statistical analyses.
Laboratory Assessment
The CD4+ cell counts, hemoglobin and ß2-microglobulin
levels, and hematocrit were obtained. For analysis, these were treated as
continuous variables. The CD4+ cell count and ß2-microglobulin
level were transformed using the natural logarithm.
DIAGNOSIS OF HIV-D
The primary end point for all analyses was the diagnosis of HIV-D. A
standardized algorithm was used to diagnose HIV-D, based on data from the
neurologic, neuropsychological, psychiatric, and functional assessments.19 To receive the HIV-D diagnosis, subjects had to fulfill
cognitive criteria based on a set of test cutoff scores, as well to report
a deficit in at least 1 of 8 Instrumental Activities of Daily Living items.
In addition subjects were required to meet fixed criteria for either neurologic
or neuropsychiatric problems characteristic of HIV-D.
DATA ANALYSIS
The primary outcome variable for this investigation was the time from
enrollment to the development of HIV-D, as determined at a subsequent follow-up
visit. The original cohort consisted of 272 subjects; however, 71 of these
were diagnosed as having HIV-D at the baseline visit. An additional 55 subjects
did not have follow-up (postbaseline) assessments for HIV-D. All analyses
were performed on the resulting cohort of 146 subjects. For subjects who did
not develop HIV-D, the follow-up time was censored at the last available visit
at which an assessment for HIV-D was performed.
The analytic strategy focused on examination of the associations between
independent variables measured at the initial study visit (baseline) and the
time to development of HIV-D. The Cox proportional hazards regression model
was used.25 An initial set of analyses was
performed to examine these associations separately for each of the independent
variables described earlier. A best subsets model selection procedure based
on the score statistic26 was used in conjunction
with clinical judgment to help identify reasonable Cox proportional hazards
regression models for time to development of HIV-D. Two sets of multiple regression
analyses were performed: one that included all of the individual neuropsychological
test scores as independent variables, and another that instead used the composite
neuropsychological test scores. All Cox proportional hazards regression analyses
included study site as a stratification factor.
Baseline variables were compared among subjects who did and did not
reach the end point of HIV-D using t tests or  2 tests, as appropriate. A Kaplan-Meier curve was constructed for the
time to dementia outcome.25 All analyses were
performed at the 5% level of significance (2-tailed).
RESULTS
FOLLOW-UP
The follow-up experience of the 146 subjects was as follows: 146 at
6 months, 126 at 12 months, 99 at 18 months, 58 at 24 months, and 29 at 30
months. There were 33 subjects who prematurely dropped out of the study, 23
because of death.
DEMOGRAPHICS
During the course of follow-up, 45 of the 146 subjects met criteria
for incident HIV-D. Baseline characteristics of the subjects who did and did
not become demented are listed in Table
1 and Table 2. Compared
with the subjects who did not become demented, those who became demented were
more likely to be female, nonwhite, have higher macroneurologic and motor
Unified Parkinson Disease Rating Scale scores, have lower hematocrit and hemoglobin
levels, and have higher ß2-microglobulin levels. They were
also more likely to have poorer role function, Karnofsky performance scale23 and physical function scores, and higher Center for
Epidemiologic Studies–Depression Scale scores. A Kaplan-Meier curve
summarizing time to reach the dementia end point across the entire group of
patients is shown in Figure 1. In
our cohort of 146 subjects, the estimated probability of incident HIV-D was
approximately 25% at 12 months and 40% at 24 months.
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Table 1. Summary Statistics for Demographic and Medical Variables Measured
at the Initial Visit*
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Table 2. Summary Statistics for Neuropsychological Tests Administered
at the Initial Visit*
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UNIVARIATE ANALYSES
We first examined the associations between the presence of individual
features noted on the initial evaluation and incident dementia; results are
summarized in Table 3 and Table 4. For individual tests in the neuropsychological
battery, defective scores on Timed Gait performance, Verbal Fluency, Grooved
Pegboard, and Digit Symbol tests were associated with an increased risk of
incident dementia (Table 3). Also,
the composite z scores for attention-memory, psychomotor
speed, and executive function, as well as the diagnosis of MCMD at baseline,
were associated with an increased risk of incident dementia (Table 3). Survival curves for patients with and without a diagnosis
of MCMD at baseline are shown in Figure 1.
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Table 3. Hazard Ratios for Univariate Analyses of Neuropsychological
Test Results Administered at the Initial Visit*
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Table 4. Hazard Ratios for Univariate Analyses of Demographic and Medical
Variables Measured at the Initial Visit*
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For demographic and medical variables, female sex, race (nonwhite),
increased abnormalities on the neurologic examination, the presence of extrapyramidal
signs, and a history of HIV-related medical symptoms were all associated with
an increased risk of incident HIV-D. Increased risk was also noted in subjects
with higher reported role or physical function difficulties and with higher
depression scores. Finally, lower hematocrits and hemoglobin levels and higher ß2-microglobulin levels were associated with an increased risk of HIV-D
(Table 4).
MULTIVARIATE ANALYSES
Best-subsets model selection was used to generate a series of multivariate
models for the HIV-D end point. A series of models containing 1 to 8 independent
variables were generated. The first model considered demographic and medical
variables and individual neuropsychological test results as potential covariates.
The selected model included depression as assessed with the Center for Epidemiologic
Studies–Depression Scale, sex, Digit Symbol Test, Verbal Fluency Test,
history of HIV-related diagnoses, and Timed Gait performance (Table 5). A second, similar model was created using the cognitive
domain scores. The selected model included depression, sex, executive function,
history of HIV-related diagnoses, Timed Gait performance, and the presence
of MCMD (Table 6).
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Table 5. Selected Multivariate Model, Including Individual Neuropsychological
Test Results*
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Table 6. Selected Multivariate Model, Including Neuropsychological
Summary Scores*
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COMMENT
This prospective study identified a set of variables that were associated
with increased risk of dementia in a cohort of HIV-positive subjects identified
as having cognitive deficits and/or severe immunosuppression. In the univariate
analyses, variables were identified in all of the categories evaluated. For
medical variables, similar to observations in a separate cohort studied by
McArthur et al,1 an increased risk of dementia
was associated with history of HIV-related medical symptoms and lower hemoglobin
levels. In addition, lower hematocrit and increased ß2-microglobulin
levels were associated with greater risk, consistent with previous observations
linking these variables with cognitive deficits and dementia in HIV-D. The
observation that abnormalities on the neurologic examination and the presence
of extrapyramidal signs were associated with an increased risk is also consistent
with the observation that these features are typically noted as parts of the
AIDS dementia complex. It is, therefore, logical to expect that in some cases
their presence would precede the actual onset of dementia. Similarly, depression
is one of the defining features of the dementia complex and, thus, logically
might precede the onset of the entire syndrome. Lower role and physical function
scores were associated with an increased risk of dementia; this may represent
the earliest manifestation of the dementing process.
Poor performance on a series of neuropsychological tests, including
Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol, was also associated
with an increased risk of incident dementia. Similarly, poorer performance
in the following cognitive domains was associated with greater risk: attention-memory,
psychomotor, and executive function. In an analysis of data from the Multicenter
AIDS Cohort Study, Sacktor et al5 reported
that sustained psychomotor slowing was associated with an increased hazard
of dementia, AIDS, and death. Cognitive decline in other domains was not predictive,
however. Their analysis differs from ours because we considered only performance
at the initial visit, as opposed to change in performance over time. In addition,
the current study specifically recruited individuals with cognitive deficits
or advanced immunosuppression, perhaps increasing the probability that they
would become demented.
The association between cognitive performance at baseline and later
dementia suggests that poorer performance could represent the earliest sign
of a dementing process. However, the significance of mild cognitive changes
in individuals who are HIV positive has been unclear. To our knowledge, it
has not been previously established whether the presence of subtle cognitive
deficits has any implications for the later development of dementia. Further,
it has not been clear whether the presence of MCMD has any relation to dementia.
This study suggests that at least in some cases, cognitive deficits and MCMD
are related to the later advent of dementia.
Female sex may also be a risk factor for dementia. This observation
is consistent with previous reports that HIV-positive women have more rapid
progression of neurologic signs and symptoms.27
The multivariate models presented herein were selected from several
candidate models and require validation in other samples. Still, they provide
some insight into the independent contribution of the variables identified
in the univariate analyses. It is notable that sex, depression, Timed Gait
performance, and a history of HIV-related diagnoses are included in both models.
In addition, both models implicate poorer executive function as an independent
risk factor for dementia. Since executive dysfunction is often one of the
earliest cognitive changes noted in HIV, this suggests that there may be a
common underlying mechanism between dementia and early cognitive change. Finally,
in the second model presented, MCMD remained a significant risk factor for
dementia, independent from depression and executive dysfunction. Thus, the
presence of this syndrome seems to have unique predictive value, over and
above the presence of some features that contribute to its diagnosis.
AUTHOR INFORMATION
Accepted for publication July 28, 2000.
This study was supported by the Charles A. Dana Foundation, New York,
NY, and grants RR00645 and 5MO1 00044 from the National Institutes of Health,
Bethesda, Md.
Members of the Dana Consortium on the Therapy
of HIV–Dementia and Related Cognitive Disorders
Columbia University, New York, NY: Karen S.
Marder, MD, MPH; Yaakov Stern, PhD; Steven Albert, PhD; George Todak, MSW;
Ronda Clouse, RN; Carmen Polanco, MS; Richard Mayeux, MD, MS. Johns Hopkins University, Baltimore, Md: Ned Sacktor, MD; Ola A. Selnes,
PhD; Deborah Hasenaue, MA; Deneen Esposito, BA; Justin McArthur, MB,BS, MPH. University of Rochester, Rochester, NY: Giovanni Schifitto,
MD; Michael P. McDermott, PhD; Donna Palumbo, PhD; Connie Orme, BA; Charlyne
Hickey, RN; Cindy Casaceli, MBA; Lisa Rumfola, RN; Carol Zimmerman, RN; Karl
Kieburtz, MD, MPH. Northwestern University Medical School,
Chicago, Ill: Leon Epstein, MD.
From the Departments of Neurology (Drs Stern, Albert, and Marder) and
Psychiatry (Dr Stern), Sergievsky Center and the Taub Institute, Columbia
University College of Physicians and Surgeons, New York, NY; New York Presbyterian
Hospital, New York (Drs Stern and Marder); Departments of Neurology and Biostatistics,
University of Rochester Medical Center, Rochester, NY (Dr McDermott); Department
of Neurology (Drs Palumbo, Schifitto, and Kieburtz) and Biostatistics (Drs
Palumbo and Schifitto), University of Rochester School of Medicine and Dentistry,
Rochester; Department of Neurology (Drs Selnes and McArthur) and Epidemiology
(Dr McArthur), The Johns Hopkins University School of Medicine, Baltimore,
Md; Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore
(Dr Sacktor); and the Department of Pediatrics, Children's Memorial Hospital,
Northwestern University Medical School, Chicago, Ill (Dr Epstein).
Corresponding author and reprints: Yaakov Stern, PhD, Sergievsky
Center, 630 W 168th St, New York, NY 10032 (e-mail: ys11{at}columbia.edu).
REFERENCES
| |
1. McArthur JC, Hoover DR, Bacellar H, et al for the Multicenter AIDS Cohort Study. Dementia in AIDS patients: incidence and risk factors. Neurology. 1993;43:2245-2252.
FREE FULL TEXT
2. Childs EA, Lyles RH, Selnes OA, et al. Plasma viral load and CD4 lymphocytes predict HIV-associated dementia
and sensory neuropathy. Neurology. 1999;52:607-613.
FREE FULL TEXT
3. Chiesi A, Vella S, Dally LG, et al for AIDS in Europe Study Group. Epidemiology of AIDS dementia complex in Europe. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;11:39-44.
FULL TEXT
|
ISI
| PUBMED
4. Baldeweg T, Catalan J, Gazzard BG. Risk of HIV dementia and opportunistic brain disease in AIDS and zidovudine
therapy. J Neurol Neurosurg Psychiatry. 1998;65:34-41.
FREE FULL TEXT
5. Sacktor NC, Bacellar H, Hoover DR, et al. Psychomotor slowing in HIV infection: a predictor of dementia, AIDS
and death. J Neurovirol. 1996;2:404-410.
ISI
| PUBMED
6. Report of a Working Group of the American Academy of Neurology AIDS
Task Force. Nomenclature and research case definitions for neurological manifestations
of human immunodeficiency virus type-1 (HIV-1) infection. Neurology. 1991;41:778-785.
FREE FULL TEXT
7. Fahn S, Marsden C, Calne D. Recent Developments in Parkinson's Disease. Florham Park, NJ: Macmillan Healthcare Information; 1987.
8. Butters N, Grant I, Haxby J, et al. Assessment of AIDS-related cognitive changes: recommendations of the
NIMH Workshop on Neuropsychological Assessment Approaches. J Clin Exp Neuropsychol. 1990;12:963-978.
ISI
| PUBMED
9. Rey A. L'examen psychologique dans les cas d'encephalopathie traumatique. Arch Psychol. 1941;28:286-340.
10. Wechsler D. Wechsler Adult Intelligence Scale-Revised. New York, NY: Psychological Corp; 1981.
11. Klove H. Clinical neuropsychology. Med Clin North Am. 1963;46:1647-1658.
12. Benton AL, Hamsher KD. Multilingual Aphasia Examination. Iowa City: University of Iowa; 1976.
13. Flowers KA, Robertson C. The effects of Parkinson's disease on the ability to maintain a mental
set. J Neurol Neurosurg Psychiatry. 1985;48:517-529.
FREE FULL TEXT
14. Richards M, Cote LJ, Stern Y. Executive function in Parkinson's disease: set-shifting or set-maintenance? J Clin Exp Neuropsychol. 1993;15:266-279.
ISI
| PUBMED
15. Selnes OA, Jacobson L, Machado AM, et al for the Multicenter AIDS Cohort Study. Normative data for a brief neuropsychological screening battery. Percept Mot Skills. 1991;73:539-550.
FULL TEXT
|
ISI
| PUBMED
16. Concha M, Selnes OA, McArthur J, et al. Normative data for a brief neuropsychologic test battery in a cohort
of injecting drug users. Int J Addict. 1995;30:823-841.
ISI
| PUBMED
17. Stern Y, Marder K, Bell K, et al. Multidisciplinary baseline assessment of homosexual men with and without
human immunodeficiency virus infection, III: neurologic and neuropsychological
findings. Arch Gen Psychiatry. 1991;48:131-138.
FREE FULL TEXT
18. Marder K, Stern Y, Malouf R, et al. Neurologic and neuropsychological manifestations of human immunodeficiency
virus infection in intravenous drug users without acquired immunodeficiency
syndrome: relationship to head injury. Arch Neurol. 1992;49:1169-1175.
FREE FULL TEXT
19. The Dana Consortium on Therapy for HIV–Dementia and Related Cognitive
Disorders. Clinical confirmation of the American Academy of Neurology algorithm
for HIV-1-associated cognitive/motor disorder. Neurology. 1996;47:1247-1253.
FREE FULL TEXT
20. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities
of daily living. Gerontologist. 1969;9:179-186.
ISI
| PUBMED
21. Katz S, Ford A, Moskowitz R, et al. Studies of illness in the aged: the index of ADL. JAMA. 1963;183:914-919.
22. Stewart AL, Ware JE. Measuring Function and Well-being: The Medical Outcomes
Study Approach. Durham, NC: Duke University Press; 1993.
23. Karnofsky DA, Abelman WH, Carver LF, et al. The use of nitrogen mustards in the palliative treatment of carcinoma. Cancer. 1948;1:634-656.
FULL TEXT
|
ISI
24. Radloff LL. The CES-D: a self-report depression scale for research in the general
population. Appl Psychol Meas. 1977;1:385-401.
FULL TEXT
25. Cox DR, Oakes D. Analysis of Survival Data. London, England: Chapman & Hall; 1984.
26. SAS Institute Inc. SAS/STAT Software: Changes and Enhancements Through
Release 6.11. Cary, NC: SAS Institute Inc; 1996.
27. Liu X, Marder K, Stern Y, et al. Gender differences in HIV-related neurological progression in a cohort
of injecting drug users followed for 3.5 years. J Neuro-AIDS. 1996;1:17-29.
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