Mild Cognitive Impairment and Risk of Mortality in HIV-1 Infection

Wilkie, Frances L.; Goodkin, Karl; Eisdorfer, Carl; Feaster, Daniel J.; Morgan, Robert O.; Fletcher, Mary A; Blaney, Nancy T.; Baum, Marianna K.; Szapocznik, José

doi:10.1176/jnp.10.2.125

Cited by 73 publications

(52 citation statements)

References 29 publications

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“…Depression may alter the course of HIV infection by impairing immune function or influencing behavior. There is evidence that depression is a risk factor for HIV (McDermott et al, 1994), but depression is also a risk factor for increased substance abuse, which may lead to an enhaced risk of HIV infection (Regier et al, 1990) and is associated with a higher mortality rate (Wilkie et al, 1998;Ickovics et al, 2001).…”

Section: Affective Disordersmentioning

confidence: 99%

Psychiatric Complications in Human Immunodeficiency Virus Infection

Koutsilieri¹,

Scheller²,

Sopper³

et al. 2002

J. of Neurovirology

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Human immunodeficiency virus (HIV) infection is associated with psychiatric complications, including cognitive impairment, affective disorders, and psychosis. These psychiatric complications impair quality of life, affect disease prognosis, and impede treatment by compromising medication adherence. They also increase the likelihood of HIV transmission, either directly or via their high prevalence rate among drug abusers. In this article, the authors provide a brief overview of the most common psychiatric complications associated with HIV infection and discuss the role of dopamine as a link between psychiatric manifestations and the progression of immunodeficiency infection.

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Section: Affective Disordersmentioning

confidence: 99%

Psychiatric Complications in Human Immunodeficiency Virus Infection

Koutsilieri¹,

Scheller²,

Sopper³

et al. 2002

J. of Neurovirology

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“…A rapid disease progression and shortened survival has been associated with lower CD4 counts, lower hemoglobin, high serum B2-microglobulin, high neopterin levels, high interleukin 6, low anti-p17 and p24 antibodies, and specific AIDS defining illnesses (Chene et al, 1996;Childs et al, 1999;Lefrere et al, 1998;Mayne et al, 1996;Wilkie et al, 1998). Despite the use of these laboratory markers in estimating prognosis, significant variation in the natural history of HIV-1 infection remains unexplained.…”

Section: Introductionmentioning

confidence: 99%

“…HIV-infected patients with fewer years of education, older age, lower premorbid IQ and lower occupational attainment are at greater risk for HIV-related cognitive impairments (Arendt, Hefter, Nelles, Hilperath, & Strohmeyer, 1993;Basso & Bornstein, 2000;Satz et al, 1993 et al, 1994), factors that have also been interpreted as indirect markers of brain reserve capacity (Satz, 1993). These findings, coupled with studies showing that patients with neurocognitive impairments are at greater risk for AIDS and death (Ellis et al, 1997;Heyes et al, 1991;Karlsen et al, 1995;Mayeux et al, 1993;Wilkie et al, 1998), provide indirect evidence that education, IQ, and occupational history are markers significantly associated with HIV disease progression. By contrast, the results of studies examining the influence of depressed mood on HIV morbidity and mortality have been more equivocal.…”

Section: Introductionmentioning

confidence: 99%

Psychosocial Risk Factors of HIV Morbidity and Mortality: Findings from the Multicenter AIDS Cohort Study (MACS)

Farinpour

Miller

Satz

et al. 2003

Journal of Clinical and Experimental Neuropsychology

160

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Despite the use of laboratory markers in estimating HIV prognosis, significant variation in the natural history of HIV-1 infection remains unexplained. Recent studies suggest psychosocial risk factors have important prognostic significance in HIV disease. The objective of the present study was to examine the prognostic influence of age, general intellectual functioning, and emotional distress across the spectrum of HIV disease progression. The study sample was drawn from the Multicenter AIDS Cohort Study (MACS), a 13-year, prospective study of HIV-seropositive men recruited from four study centers across the country. The participants were 1,231 HIV-seropositive MACS participants, followed from baseline (median 8/15/87) to the end of the observation period (12/15/98). HIV disease progression was evaluated with respect to three outcome measures: (1) number of years from baseline testing to the first AIDS defining illness (progression to AIDS), (2) years from baseline to HIV-dementia (progression to dementia), and (3) years from baseline to death (survival). The influence of psychosocial risk factors on outcome measures was evaluated using survival analyses. General intellectual functioning, age, and somatic symptoms of depression, were found to be significant predictors of HIV disease progression and survival. Older age at baseline was associated with a more rapid progression to dementia and death. Lower Shipley IQ estimates were associated with a more rapid disease progression (AIDS and dementia) and shortened survival. Somatic symptoms of depression were associated with shortened survival. In addition, age, IQ, and somatic symptoms of depression, had an additive effect with an increase in the number of risk factors associated with accelerated disease progression and shortened time to death. These findings remained consistent, despite controlling for baseline CD4 and HIV medication use. Psychosocial cofactors are important in understanding HIV disease progression. Methods for estimating HIV prognosis may become more reliable if psychosocial factors are considered. Future research will clarify if psychosocial risk factors reflect central nervous system integrity, brain reserve capacity or mediate morbidity and mortality through social economic status, access to health care and other social correlates.

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“…Changes in cognition, depression, and fitness have marked mortality implications in this group [22,[32][33][34][35][36][37][38][39][40][41][42][43][44][45].…”

mentioning

confidence: 99%

The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes

Golomb

Criqui

White

et al. 2004

Controlled Clinical Trials

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There has been persistent controversy regarding possible favorable or adverse effects of statins or of cholesterol reduction on cognition, mood and behavior (including aggressive or violent behavior), muscle function, and quality of life. The UCSD Statin Study seeks to ascertain the beneficial or adverse effects of statin cholesterol-lowering drugs on a set of noncardiac endpoints, including cognition, behavior, and serotonin biochemistry. The study will enroll 1000 subjects (minimum 20% female) of mixed ethnicity from San Diego. Subjects must be age 20 and older, postmenopausal if female, without known cardiovascular disease or diabetes, and with LDLcholesterol between 115 and 190 mg/dl. Subjects will be randomized to a double-blind, placebocontrolled trial with assignment 1/3, 1/3, 1/3 to placebo, simvastatin 20 mg, or pravastatin 40 mg (equipotent LDL-cholesterol-lowering doses for drug arms with simvastatin and pravastatin chosen to represent the extremes of the lipophilicity spectrum) for 6 months of treatment followed by 2 months postcessation follow-up. Primary outcomes are cognition (cognitive battery), irritability/aggression (behavior measure), and serotonin (gauged by whole blood serotonin), assessed as the difference between baseline and 6 months, judging combined statin groups vs. placebo. Secondary outcomes include mood (CES-D and Wakefield depression inventory), quality of life (SF-12V), sleep (Leeds sleep scale, modified), and secondary aggression measures (Conflict Tactics Scale; Overt Aggression Scale, Modified). Cardiovascular reactivity will be examined in a 10% subset. As additional secondary endpoints, primary and selected secondary outcomes will be assessed by statin assignment (lipophilic simvastatin vs. hydrophilic pravastatin). "Reversibility" of changes, if any, at 2 months postcessation will be determined. If effects (favorable or unfavorable) are identified, we will seek to ascertain whether there are baseline variables that predict who will be most susceptible to these favorable or adverse noncardiac effects (i.e., effect modification). NIH Public Access BackgroundStatins are important and widely prescribed drugs, with well-documented and incontrovertible cardiac benefits. However, controversy remains regarding the existence and impact of noncardiac effects, including central nervous system (CNS) effects. The University of California-San Diego (UCSD) Statin Study, a National Institutes of Health/ National Heart Lung and Blood Institute-funded double-blind, placebo-controlled study, seeks to address these issues through a complex battery of tests assessing noncardiac outcomes pertaining to cognition, behavior, quality of life, and biochemistry, among other endpoints. This paper provides the general methodology employed and addresses certain theoretical issues in study design.Statin cholesterol-lowering drugs (HMG-CoA reductase inhibitors) are the most prescribed drugs in the United States and the world and contributed substantially to prescription drug cost increases in 200...

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Mild Cognitive Impairment and Risk of Mortality in HIV-1 Infection

Cited by 73 publications

References 29 publications

Psychiatric Complications in Human Immunodeficiency Virus Infection

Psychiatric Complications in Human Immunodeficiency Virus Infection

Psychosocial Risk Factors of HIV Morbidity and Mortality: Findings from the Multicenter AIDS Cohort Study (MACS)

The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes

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