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. Author manuscript; available in PMC: 2007 Apr 12.
Published in final edited form as: Arch Clin Neuropsychol. 2007 Feb 6;22(2):187–195. doi: 10.1016/j.acn.2006.12.006

Frequency and predictors of self-reported prospective memory complaints in individuals infected with HIV

Steven Paul Woods a,*, Catherine L Carey b, Lisa M Moran a, Matthew S Dawson a, Scott L Letendre c, Igor Grant a, The HIV Neurobehavioral Research Center (HNRC) Group
PMCID: PMC1851919  NIHMSID: NIHMS19764  PMID: 17289343

Abstract

Failures of episodic retrospective memory (RetM) are among the most frequently reported cognitive complaints endorsed by individuals living with HIV infection. The present study sought to examine the nature, frequency, and determinants of self-reported complaints of prospective memory (ProM) in HIV, which is a singly dissociable and ecologically relevant aspect of episodic memory involving the execution of future intentions. Seventy-five HIV seropositive individuals and 60 seronegative volunteers were administered the Prospective and Retrospective Memory Questionnaire (PMRQ) as part of extensive neuropsychological, psychiatric, and medical research assessments. The HIV sample endorsed more frequent ProM complaints in daily life than the seronegative group, particularly on items requiring self-initiated cue detection and retrieval. Within both study groups, ProM complaints were significantly more frequent than RetM complaints. Although the HIV sample was impaired relative to the seronegative group on an objective, performance-based ProM test, self-reported ProM complaints did not correspond to actual ProM abilities. However, greater frequency of self-reported ProM complaints was moderately associated with increased fatigue, as well as with symptoms of anxiety and depression. Consistent with prior research on RetM in HIV, results indicate that affective distress contributes to a metamemory deficit for HIV-associated ProM impairment, which highlights the potential importance of assessing both self-reported and performance-based ProM in clinical and research neuroAIDS evaluations.

Keywords: Human immunodeficiency virus, Neuropsychological assessment, Self-report, Fatigue, Episodic memory, Metacognition

Individuals infected with the human immunodeficiency virus (HIV) commonly endorse cognitive complaints in their daily lives, such as problems with multitasking, organizing day-to-day activities, and quickly processing complex information (e.g., Maj et al., 1994; Stern et al., 1991). Complaints of episodic memory are perhaps the most frequently reported cognitive difficulties in HIV (e.g., Maj et al., 1994). Although objective HIV-associated memory impairments are modestly related to self-reported memory complaints (e.g., Bassel, Rourke, Halman, & Smith, 2002), metamemory deficits (i.e., misconceptions regarding one’s own memory capabilities) are nevertheless common in HIV. Increased symptoms of depression (Rourke, Halman, & Bassel, 1999a; Rourke, Halman, & Bassel, 1999b; van Gorp et al., 1991) and fatigue (Millikin, Rourke, Halman, & Power, 2003) best predict the over-reporting of objective HIV-associated memory deficits, whereas mild anosagnosia (i.e., under-reporting of a genuine memory impairment) is related to executive dysfunction (e.g., Rourke et al., 1999b).

An important distinction is now being made between two primary components of episodic memory: viz., retrospective memory (RetM) and prospective memory (ProM). RetM, which historically has been the exclusive focus of objective and self-reported memory research in HIV, refers to the recollection of past experiences in response to overt prompts (e.g., standard tests of list learning and recall measure RetM). RetM is a necessary, but not sufficient component of ProM, which denotes the ability to execute a future intention in the absence of explicit cues (i.e., “remembering to remember”). Examples of ProM in daily life include remembering to take a medication at a particular time of day or remembering to purchase groceries on the way home from work. ProM is hypothesized to be a stronger contributor to the independent performance of several instrumental activities of daily living (IADL) than RetM (e.g., medication adherence; Park & Kidder, 1996). As such, research is needed to better understand the nature, extent, and predictors of HIV-associated ProM deficits and complaints.

Recent studies using objective tests of ProM indicate that HIV infection is associated with a breakdown in the strategic (i.e., executive) encoding and retrieval aspects of retrieving future intentions. Carey, Woods, Rippeth, Heaton, Grant, & The HNRC Group (2006) were the first to publish evidence of performance-based ProM impairment in HIV, which was characterized by deficient time-and event-cued ProM, but normal performance on a multiple-choice recognition posttest. HIV-associated ProM impairment correlated with worse performance on measures of strategic verbal encoding, working memory, executive functions, and complex information processing speed. The ecological relevance of HIV-associated ProM impairment on objective tasks is supported by preliminary data regarding its association with engagement in high-risk behaviors (e.g., injection drug use; Martin et al., in press) and medication nonadherence (Beauvais, Raskin, Dieckhaus, Miller, & Rosen, 2005) in HIV-infected polysubstance users. Importantly, the neuropathogenesis of HIV-associated ProM impairment may be dissociable from RetM as evidenced by data showing that biomarkers of macrophage activation and axonal injury predict ProM, but not RetM in HIV (Woods et al., 2006). As such, ProM may capture a unique and ecological aspect of cognitive functioning that is ubiquitous in daily life but not currently probed by traditional memory assessment techniques.

Formal assessment of ProM may therefore become integral to the clinical evaluation of neuropsychological functioning in persons infected with HIV. Although the literature on objective ProM impairment in the laboratory is steadily growing, no prior studies have examined whether HIV-infected persons subjectively experience ProM failures in their daily lives or whether such complaints relate to objective, performance-based ProM abilities. Therefore, the current study was conducted to evaluate these important questions, as well to identify the medical, psychiatric, and cognitive determinants of self-reported ProM complaints in HIV. It was hypothesized that: (1) both ProM and RetM complaints are more common in individuals infected with HIV versus seronegative volunteers; (2) ProM complaints are more frequent in persons with advanced HIV disease; (3) ProM complaints are modestly associated with neuropsychological deficits on objective tests of ProM, RetM, working memory, and executive functions; and (4) ProM complaints are associated with increased symptoms of affective distress, particularly depression and fatigue.

1. Method

1.1. Participants

The study sample included 75 HIV seropositive persons (HIV+) as indicated by enzyme linked immunosorbent assays and a Western Blot confirmatory test and 60 seronegative healthy comparison volunteers (HC). All HIV+ participants and 57% of the HC sample (n = 34) were recruited to participate in a Federally-funded, observational study of ProM in HIV, whereas the remaining 43% (n = 26) of the HC participants were evaluated as part of their participation in the HIV Neurobehavioral Research Center. As such, not all ancillary measures (e.g., non-ProM cognitive tasks) were available for these 26 HCs. The University Human Research Protections Program approved these studies. Potential participants were excluded if they reported a history of psychiatric (e.g., mental retardation, psychotic disorders, learning disabilities, attention-deficit/hyperactivity disorder, and bipolar disorder) or neurological (e.g., seizure disorders, closed head injuries with loss of consciousness greater than 15 min, and central nervous system neoplasms or opportunistic infections) diagnoses. Additionally, participants were excluded if they met Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria for substance dependence within the past six months (e.g., cocaine or methamphetamine dependence) or if they exhibited a positive urine toxicology screening for illicit substances on the day of evaluation.

Table 1 displays the demographic and psychiatric characteristics of the study groups, who were comparable for age, education, and ethnic identity (all ps > 0.10). There was, however, a significantly greater proportion of women in the HC sample, χ2 (1, 133) = 27.9, p < .0001. As concerns the clinical and treatment characteristics of the HIV+ group at the time of evaluation, approximately 92% were diagnosed with AIDS and the median HIV RNA viral load (log10 c/ml) in plasma was 1.69 (interquartile range [IQR] = 1.69, 2.87). The median current and nadir CD4 lymphocyte counts were 524 (IQR = 325, 801) and 195 (IQR = 44, 323) cells/μl, respectively. Seventy-seven percent of individuals in the HIV+ cohort were prescribed highly active antiretroviral therapies (HAART).

Table 1.

Demographic and Psychiatric Characteristics of the HIV+ and HC Study Samples

Variable HC (n = 60) HIV+ (n = 75) p
Demographic characteristics
 Age (years) 42.9 (11.7) 45.3 (9.4) 0.205
 Education (years) 14.5 (2.2) 13.7 (3.0) 0.138
 Gender (% women) 43.3% 5.3% <0.0001
 Ethnicity (% Caucasian) 56.7% 66.7% 0.234
Psychiatric characteristics
 Lifetime substance dependencea (%) 20.0% 52.0% 0.0001
 Lifetime major depressive disordera (%) 37.0% 48.0% 0.235
 Lifetime generalized anxiety disorderb (%) 9.1% 5.3% 0.435
Profile of Mood States
 Depression 5.7 (8.4) 9.2 (10.4) 0.003
 Anxiety 6.1 (5.3) 9.6 (7.1) 0.003
 Fatigue 5.1 (5.6) 9.0 (6.8) 0.0002
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Note: Data represent means (with S.D.) unless otherwise indicated.

a

HC n = 46.

b

HC n = 34.

1.2. Materials and procedure

After providing written, informed consent, all participants completed the Prospective and Retrospective Memory Questionnaire (PRMQ; Smith, Della Sala, Logie, & Maylor, 2000). The PRMQ is a 16-item, self-report inventory that measures the frequency with which perceived memory difficulties occur in everyday life on a 5-point Likert-type scale that ranges from 1 (“never”) to 5 (“very often”). The PRMQ includes eight RetM complaints, for example: “How often do you forget something that you were told a few minutes before?” The remaining eight items target ProM complaints, which are separated into four self-cued (e.g., “How often do you forget appointments if you are not prompted by someone else or by a reminder, such as a diary or a calendar?”) and four environmentally-cued (e.g., “How often do you forget to buy something you planned to buy, like a birthday card, even when you see the shop?”) ProM complaints. Prior research supports the internal consistency (Cronbach’s alphas ≥.80), factor structure (Crawford, Smith, Maylor, Della Sala, & Logie, 2003), and predictive validity (Smith et al., 2000; Zeintl, Kliegel, Rast, & Zimprich, 2006) of the PRMQ.

The following tests were selected from the broader neuropsychological battery to evaluate their correspondence with self-reported ProM complaints: (1) Self-Ordered Pointing Task (SOPT Total Errors; Petrides & Milner, 1982); (2) California Verbal Learning Test – Second edition (CVLT-II Long Delay Free Recall; Delis, Kramer, Kaplan, & Ober, 2000); (3) Tower of London – Drexel (ToL Total Move Score; Culbertson & Zilmer, 2001); (4) Trail Making Test (TMT Part B minus A; Reitan & Wolfson, 1985); and (5) the Memory for Intentions Screening Test (MIST Summary Score; Raskin, 2004). The MIST is a standardized test with scores ranging from 0 to 48 that is comprised of eight ProM tasks, which are counterbalanced on the following characteristics: (1) a 2-min or 15-min delay; (2) a verbal (e.g., “In 2 min, ask me what time this session ends today”) or physical (e.g., “In 15 min, use that paper to write down the number of medications you are currently taking”) response; and (3) a time-based (e.g., “In 15 min, tell me that it is time to take a break”) or event-based (e.g., “When I hand you a postcard, self-address it”) cue. Word search puzzles are provided as a distracter task to prevent overt rehearsal of the prescribed intentions. Prior research supports the construct validity of the MIST in healthy adults (Carey et al., 2006; Raskin, 2004), schizophrenia (Woods, Twamley, Dawson, Narvaez, & Jeste, in press), and HIV disease (Beauvais et al., 2005; Carey et al., 2006; Woods et al., 2006).

Finally, the Profile of Mood States (POMS; McNair, Lorr, & Droppleman, 1981) and Composite International Diagnostic Interview (CIDI version 2.1; World Health Organization, 1998) were administered to assess affective distress and provide relevant psychiatric diagnoses. The POMS is a 65-item, self-report measure of current mood states in which participants rate various adjectives (e.g., “sluggish”) and brief phrases (e.g., “sorry for things done”) on a 5-point Likert-type scale ranging from 0 (“not at all”) to 4 (“extremely”). Items on the POMS comprise several different subscales, including Depression-Dejection, Tension-Anxiety, and Fatigue-Inertia, for which higher scores indicate greater distress. The CIDI is a computer-assisted structured interview used to provide lifetime DSM-IV diagnoses of major depressive disorder, generalized anxiety disorder, and substance-related disorders (i.e., operationalized herein as the presence of alcohol dependence and/or any drug dependence greater than six months prior to assessment).

1.3. Statistical analysis

The study sample provided sufficient statistical power for the primary analyses to detect medium univariate between-group (N = 135, α= .05, β= 0.82) and correlational within-group (HIV+ n = 75, α= .05, β= 0.82) effect sizes (Erdfelder, Faul, & Buchner, 1996). A repeated measures analysis of variance (ANOVA) was conducted with HIV serostatus (HIV+ versus HC) and memory type (ProM versus RetM) as the between- and within-subjects factors, respectively. Planned follow-up comparisons were made using a series of independent-and paired-samples t-tests, or their nonparametric equivalents (e.g., Wilcoxon Rank Sums Test) as determined by the Shapiro-Wilk W Test (p < .05). The unbiased Cohen’s d statistic was used as an estimate of effect size (Hedges & Olkin, 1985). In an effort to minimize Type I error, predictors of ProM complaints were selected on an a priori basis. For continuous variables, Pearson product-moment correlation coefficients (or the nonparametric Spearman’s rank order correlation coefficient) were used to evaluate relationships between the PRMQ and psychiatric factors, neuropsychological functioning, and HIV disease severity. The chi-square statistic was used for analyses consisting entirely of categorical variables. Finally, any variables that demonstrated significant associations with ProM complaints in the HIV+ cohort were simultaneously entered as predictors into a linear regression.

2. Results

Descriptive data and statistical results for the PRMQ are shown in Table 2. Main effects were observed for HIV serostatus (F [1,133] = 6.5, p = 0.012) and memory complaint type (F [1,133] = 86.3, p < 0.0001). The HIV × memory interaction term was not statistically significant, F < 1. Follow-up pairwise comparisons revealed that the HIV group reported more frequent complaints on both PRMQ ProM and PRMQ RetM scales (ps < .05). In the HIV+ sample, PRMQ ProM complaints were more frequent than PRMQ RetM complaints, z = −784.0, p < .001, Cohen’s d = 0.42 (95% confidence interval = 0.10, 0.75). The HIV effect on the PRMQ ProM scale was primarily driven by self-cued (p < .05) rather than environmentally-cued (p > .20) complaints, with the former being significantly more frequent than the latter within the HIV+ group, z = −423.5, p < .001, Cohen’s d = 0.24 (95% confidence interval = 0.08, 0.57). Post hoc analyses revealed no main effect of sex, nor an interaction between sex and HIV serostatus in predicting any PRMQ variable, Fs < 1.

Table 2.

PRMQ scores and cognitive test performance in the HIV+ and HC study samples

Variable HC (n = 60) HIV+ (n = 75) p Cohen’s d (95% CI)
PRMQ variables
 Total 34.2 (8.9) 38.7 (11.1) 0.010 0.44 (0.10, 0.78)
  ProM total 18.5 (5.0) 20.6 (6.2) 0.030 0.37 (0.02, 0.71)
   ProM self-cued 9.5 (2.6) 10.7 (3.2) 0.028 0.42 (0.08, 0.76)
   ProM environmentally-cued 9.0 (2.7) 9.9 (3.3) 0.221 0.28 (−0.06, 0.62)
  RetM total 15.7 (4.3) 18.1 (5.5) 0.005 0.48 (0.13, 0.82)
Objective cognitive test variables
 Memory for Intentions Screening Test 42.6 (5.2) 39.2 (7.2) 0.004 −0.54 (−0.88, −0.19)
 CVLT-IIa 11.5 (2.9) 9.9 (3.8) 0.042 −0.45 (−0.86, −0.04)
 Self-Ordered Pointing Testa 3.8 (1.5) 4.1 (2.2) 0.852 0.15 (−0.26, 0.55)
 TMT B-A 32.2 (15.6) 44.8 (39.9) 0.014 0.40 (0.05, 0.74)
 Tower of Londona 32.2 (17.1) 25.8 (19.8) 0.089 −0.33 (−0.74, 0.07)
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Note: CI = confidence interval; CVLT-II = California Verbal Learning Test – Second edition; HC = healthy comparison volunteers; PRMQ = Prospective and Retrospective Memory Questionnaire; ProM = prospective memory; RetM = retrospective memory; TMT B-A = Trail making Test, Part B – Part A.

a

HC group n = 34.

As displayed in Table 2, the HIV+ cohort was impaired relative to the HC group on the MIST (p < .01), even when the potential confounding influences of sex and substance dependence were entered into the statistical model. The HIV+ group also performed below the HCs on the CVLT-II and TMT B-A (ps < .05). However, Table 3 shows that there were no correlations between the PRMQ ProM scale and any objective cognitive test in either the HIV+ or HC study samples (all ps > .10).

Table 3.

Correlations between the PRMQ ProM scale, POMS, and cognitive tests in the HIV+ and HC study samples

Measure 1 2 3 4 5 6 7 8 9
HIV+ (n = 75)
 1. PRMQ ProM –
 2. MIST −0.15 –
 3. CVLT-II −0.12 0.38*** –
 4. SOPT 0.06 −0.07 −0.28* –
 5. TMT B-A 0.15 −0.39*** −0.34** 0.42*** –
 6. ToL 0.03 −0.28* −0.29* 0.43*** 0.43*** –
 7. POMS tension 0.24* −0.08 −0.03 −0.07 0.17 0.13 –
 8. POMS depression 0.28* −0.10 −0.15 0.09 0.24* 0.26* 0.71*** –
 9. POMS fatigue 0.32** −0.11 −0.07 −0.21 0.08 0.15 0.67*** 0.61*** –
HC (n = 60)
 1. PRMQ ProM –
 2. MIST −0.16 –
 3. CVLT-IIa −0.32 0.55*** –
 4. SOPTa 0.07 −0.29 −0.33 –
 5. TMT B-A 0.17 −0.37** −0.54** 0.30*** –
 6. ToLa −0.10 −0.49** −0.16 0.37* 0.19 –
 7. POMS tension 0.39** 0.04 −0.01 0.02 0.04 −0.03 –
 8. POMS depression 0.31* 0.09 0.02 0.15 −0.08 0.08 0.74*** –
 9. POMS fatigue 0.34** 0.16 0.32 0.06 −0.03 0.08 0.63*** 0.60*** –
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CVLT-II = California Verbal Learning Test – Second edition; HC = healthy comparison volunteers; MIST = Memory for Intentions Screening Test; POMS = Profile of Mood States; PRMQ = Prospective and Retrospective Memory Questionnaire; ProM = prospective memory; ToL = Tower of London; TMT B-A = Trail making Test, Part B – Part A.

a

HC group n = 34.

*

p < .05.

**

p < .01.

***

p < .001.

PRMQ ProM complaints were not significantly related to HIV disease severity, including current (ρ= −0.03, p = .77) and nadir (ρ= −0.15, p = .23) CD4 counts, HIV RNA in plasma (ρ= 0.08, p = .47), AIDS diagnosis (t = −0.96, p = .37, d = 0.27), or HAART (t = 0.05, p = .96, d = −0.02). Regarding psychiatric characteristics in the HIV+ group, PRMQ ProM complaints did not differ between individuals with and without lifetime DSM-IV diagnoses of substance dependence (t = −1.20, p = .235, d = −0.28), major depressive (t = 1.17, p = .247, d = 0.27), or generalized anxiety (t = −0.64, p = .563, d = −0.39) disorders. In contrast, PRMQ ProM complaints were significantly correlated with the POMS tension-anxiety, fatigue-inertia and depression-dejection scales in HIV (ps < .05; see Table 3). To evaluate these relationships more closely in the HIV+ sample (n = 75), the POMS subscales were subsequently entered into a linear regression as predictors of PRMQ ProM complaints, which yielded a significant overall model (R2 = .15, p = .011) to which the fatigue subscale was the only significant contributor (p = .019).

3. Discussion

To our knowledge, the present study is the first to evaluate the nature, frequency, and predictors of self-reported ProM complaints in HIV disease. Findings revealed that both RetM and ProM complaints are significantly more frequent in HIV-infected individuals than in seronegative volunteers. In both study groups, ProM complaints were significantly more frequent than RetM complaints, suggesting that ProM may be more germane than RetM to self-perceptions regarding day-to-day memory functioning. Follow-up analyses revealed that self-cued ProM complaints were significantly more common than environmentally-cued complaints and were associated with a larger between-groups effect size. In other words, subjective ProM complaints were more frequent on daily tasks that required self-initiated intention monitoring, maintenance, and retrieval strategies than on tasks for which more salient external retrieval cues were available. These data are commensurate with our working hypothesis that HIV infection is associated with a breakdown in the strategic aspects of retrieving future intentions (Carey et al., 2006). To this end, Martin et al. (in press) recently reported deficits in objective time-based (i.e., the intended action is performed after a specified time interval), but not event-based (i.e., an external stimulus serves as the intention retrieval cue) ProM in an HIV-infected polysubstance abusing cohort (cf. Carey et al., 2006). It has been hypothesized that time-based tasks place greater emphasis on self-initiated monitoring and retrieval than those that are event-based (Einstein & McDaniel, 1990); although it may be that HIV-associated ProM impairment relates to the specific executive processing demands of the particular task, rather than whether the intention is time- or event-based (Carey et al., 2006; McDaniel, Guynn, Einstein, & Breneiser, 2004). Such findings correspond to the general neuropsychological profile of HIV, which is marked by executive dysfunction, bradyphrenia, and bradykinesia, most likely resulting from neuropathology (e.g., synaptodendritic degenerative changes) in the frontal cortex, white matter, and basal ganglia (Ellis, Langford, & Masliah, 2007).

Extending prior research on RetM in HIV (e.g. Hinkin et al., 1996), results from this study revealed a metamemory deficit for HIV-associated ProM impairment. ProM complaints were not significantly related to objective neurocognitive tests of working memory, executive functions, RetM, or ProM. The small and nonsignificant association between the PRMQ ProM scale and the MIST was somewhat surprising in the context of the medium effect sizes observed for the between-groups comparisons of these two measures (ds = 0.37 and −0.54, respectively). Moreover, consistent with prior research (e.g., Carey et al., 2006; Martin et al., in press), the MIST correlated with tests of RetM and executive functions. Nevertheless, the lack of association between the PRMQ and MIST is commensurate with prior literature on the dissociation between perceived and objective ProM in traumatic brain injury (e.g., Hannon, Adams, Harrington, Fries-Dias, & Gipson, 1995) and healthy older adults (Zeintl et al., 2006). Indeed, the seronegative comparison group in this study evidenced a similar disconnect between objective and perceived ProM. Thus, although laboratory tasks of ProM may account for a very small amount of variance in day-to-day ProM complaints, individuals with HIV infection are prone to misjudge their true ProM abilities. A “metaProM” deficit such as this may increase risk of IADL dependence in persons living with HIV; for example, individuals who overestimate their ProM abilities may avoid using effective compensatory techniques, such as active encoding strategies, external reminders, and/or assistance from care providers (Knight, Harnett, & Titov, 2005). Underestimation of one’s true ProM abilities might also restrict optimal day-to-day functioning (e.g., time and resources spent developing and using unnecessary compensatory strategies), but would ostensively be less likely to threaten independent living. The relationship between expected and actual ProM performance remains to be evaluated in HIV.

Affective distress appears to be a primary contributor to the metamemory deficit for HIV-associated ProM impairment. Higher self-reported levels of current anxiety, depression, and fatigue were significantly associated with increased frequency of ProM complaints. Regression analyses revealed that fatigue was the strongest predictor of ProM complaints, accounting for approximately 10% of the variance. Such findings are not specific to ProM or HIV, as these results are similar to RetM studies in HIV (Millikin et al., 2003), multiple sclerosis (Middleton, Denney, Lynch, & Parmenter, 2006) and breast cancer (Castellon et al., 2004). For example, Millikin et al. (2003) found an association (r = .48) between fatigue and self-reported cognitive complaints, but not with objective neuropsychological performance in 68 HIV-infected men. It is not surprising that increased levels of fatigue (e.g., physical and mental sluggishness) in HIV were associated with the perception of increased complaints on self-cued ProM tasks, which place considerable demands on self-initiated monitoring and retrieval strategies. The experience of fatigue is common in persons with HIV infection and is associated with depression, poorer health-related quality of life, and greater functional disability (e.g., Henderson, Safa, Easterbrook, & Hotopf, 2005). Although these findings are correlational, they suggest that effective pharmacological, cognitive, and/or behavioral management of fatigue may be helpful in reducing the frequency of ProM complaints in HIV.

Given the relatively high frequency of ProM complaints, objective ProM deficits, and evidence of a possible metaProM dissociation, formal assessment of ProM may be integral to the clinical evaluation of neuropsychological functioning in persons infected with HIV. In addition to the self-report PRMQ, several objective, performance-based tasks are available in this regard; for example, a common informal clinical practice is for the examiner to hide an item (e.g., keys) and instruct the patient to request the hidden item at the end of the evaluation (e.g., Bakker, Schretlen, & Brandt, 2002). However, poorly standardized procedures, a restricted range of scores, the unavailability of normative data, and variable research support limit the usefulness of such techniques. In response, a few standardized measures of ProM have emerged in recent years, including the MIST (Raskin, 2004) and the Cambridge Prospective Memory Test (Wilson et al., 2005). Although these tests represent a significant advance in the assessment of ProM, their clinical utility is dependent upon future research supporting their psychometric properties and construct validity (especially ecological validity) in healthy volunteers and various clinical groups at risk for episodic memory deficits and associated IADL problems. In particular, the development and validation of demographically-adjusted (e.g., age-corrected) normative standards will be essential to their increased usefulness in clinical practice.

The most salient limitations of the current investigation are the subjective nature of the self-reported ProM complaints and the restricted HIV disease and demographic characteristics of the study samples. In particular, it is possible that the increased frequency of ProM complaints in this HIV cohort reflect a self-report bias, rather than actual daily ProM failures that would threaten independent living. Future studies should include proxy ratings of everyday ProM complaints (e.g., from significant others or caregivers) and/or performance-based measures of ProM-related IADLs (e.g., electronic monitoring of medication adherence) to more effectively evaluate the ecological validity of ProM complaints in HIV. Also of note, the robustness of the HIV disease-related analyses is clearly restricted by the use of a largely healthy study sample. Only 8% were immunosuppressed (i.e., CD4 lymphocyte counts <200 cells/μl) and 63% had undetectable HIV viral loads in plasma (i.e., HIV RNA ≤1.69 [log10 c/ml]) at the time of evaluation. As such, the frequency and predictors of ProM complaints in individuals with more advanced HIV disease remains speculative and should be a target for future research. The immune health of this sample nevertheless represents a conservative bias by showing notably increased ProM complaints and objective deficits in an asymptomatic HIV cohort. The study groups were matched on age, education, and ethnic identity, therefore suggesting that the increased frequency of ProM complaints in HIV is unlikely to be due to demographic factors. Although there was a larger proportion of women in the HC group, no main effect of sex or interaction between sex and HIV serostatus was observed for any of the PRMQ scales. This is consistent with prior studies showing no sex effects on the PRMQ ProM scale in healthy adults (e.g., Crawford et al., 2003). Nevertheless, the HIV sample was predominately comprised of well-educated men with histories of substance dependence, which may restrict the generalizeability of these data to HIV-infected women with lower levels of education and different transmission risks. Although approximately 73% of adults living with HIV are men, the number of incident AIDS cases continues to rise among women and ethnic minorities (Centers for Disease Control, 2005).

To summarize, findings from this study indicate that self-reported daily ProM complaints are elevated in persons infected with HIV and are generally more frequent than RetM complaints. Perceived ProM complaints did not correspond to demographics, HIV disease severity, substance dependence, or performance-based ProM deficits, but were instead associated with increased levels of affective distress, most notably fatigue. Extending prior research on RetM in HIV, results support the existence of a mild metamemory deficit for HIV-associated ProM impairment, which highlights the importance of assessing both self-reported and performance-based ProM in clinical and research neuropsychological evaluations of individuals living with HIV. Studies are currently underway in our laboratory to evaluate the construct, ecological, and incremental validity of ProM in HIV disease.

Acknowledgments

The San Diego HIV Neurobehavioral Research Center (HNRC) group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and includes: Director: Igor Grant, M.D.; Co-Directors: J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., and J. Allen McCutchan, M.D.; Center Manager: Thomas D. Marcotte, Ph.D.; Naval Hospital San Diego: Braden R. Hale, M.D., M.P.H. (P.I.); Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.), J. Allen McCutchan, M.D., Scott Letendre, M.D., Edmund Capparelli, Pharm.D., Rachel Schrier, Ph.D.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), Mariana Cherner, Ph.D., Steven Paul Woods, Psy.D.; Neuroimaging Component: Terry Jernigan, Ph.D. (P.I.), Christine Fennema-Notestine, Ph.D., Sarah L., Archibald, M.A., John Hesselink, M.D., Jacopo Annese, Ph.D., Michael J. Taylor, Ph.D., Brian C. Schweinsburg, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Ian Everall, FRCPsych., FRCPath., Ph.D., T. Dianne Langford, Ph.D.; Neurovirology Component: Douglas Richman, M.D., (P.I.), David M. Smith, M.D.; International Component: J. Allen McCutchan, M.D., (P.I.); Developmental Component: Ian Everall, FRCPsych., FRCPath., Ph.D. (P.I.), Stuart Lipton, M.D., Ph.D.; Clinical Trials Component: J. Allen McCutchan, M.D., J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., Scott Letendre, M.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.), Rodney von Jaeger, M.P.H.; Data Management Unit: Anthony C. Gamst, Ph.D. (P.I.), Clint Cushman, B.A., (Data Systems Manager), Michelle Frybarger, B.A., Daniel R. Masys, M.D. (Senior Consultant); Statistics Unit: Ian Abramson, Ph.D. (P.I.), Christopher Ake, Ph.D., Deborah Lazzaretto, M.S.

Dr. Carey is now in the Department of Psychiatry at the University of California, San Diego. This research was supported by National Institute of Mental Health grants R01-MH073419 to Dr. Woods and P30-MH62512 to Dr. Grant. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government. Aspects of these data were presented at the 34th Annual Meeting of the International Neuropsychological Society in Boston, Massachusetts. The authors extend their gratitude to Nancy Anderson for her assistance with the data entry, to Jennifer Marquie Beck, Ofilio Vigil, and Sarah Gibson for their help with data coding, and to Dr. Sarah Raskin for providing us with the MIST.

References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4. Washington, D.C.: American Psychiatric Association; 1994. [Google Scholar]
  2. Bakker A, Schretlen DJ, Brandt J. Testing prospective memory: Does the value of a borrowed item help people remember to get it back? The Clinical Neuropsychologist. 2002;16:64–66. doi: 10.1076/clin.16.1.64.8325. [DOI] [PubMed] [Google Scholar]
  3. Bassel C, Rourke SB, Halman MH, Smith ML. Working memory performance predicts subjective cognitive complaints in HIV infection. Neuropsychology. 2002;16:400–410. doi: 10.1037//0894-4105.16.3.400. [DOI] [PubMed] [Google Scholar]
  4. Beauvais J, Raskin S, Dieckhaus K, Miller L, Rosen MI. Prospective memory and adherence to prescribed medication [abstract] Journal of the International Neuropsychological Society. 2005;11(Suppl 1):121. [Google Scholar]
  5. Carey CL, Woods SP, Rippeth JD, Heaton RK, Grant I, the HNRC Group Prospective memory in HIV-1 infection. Journal of Clinical and Experimental Neuropsychology. 2006;28:536–548. doi: 10.1080/13803390590949494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. Journal of Clinical and Experimental Neuropsychology. 2004;26:955–969. doi: 10.1080/13803390490510905. [DOI] [PubMed] [Google Scholar]
  7. Centers for Disease Control and Prevention. HIV/AIDS surveillance Report, 2004. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2005. [Google Scholar]
  8. Crawford JR, Smith G, Maylor EA, Della Sala S, Logie RH. The Prospective and Retrospective Memory Questionnaire (PRMQ): Normative data and latent structure in a large non-clinical sample. Memory. 2003;11:261–275. doi: 10.1080/09658210244000027. [DOI] [PubMed] [Google Scholar]
  9. Culbertson WC, Zilmer EA. The Tower of London DX (TOLDX) manual. North Tonawanda, NY: Multi-Health Systems; 2001. [Google Scholar]
  10. Delis DC, Kramer JH, Kaplan E, Ober BA. The California Verbal Learning Test. 2. San Antonio, TX: The Psychological Corporation; 2000. [Google Scholar]
  11. Einstein GO, McDaniel MA. Normal aging and prospective memory. Journal of Experimental Psychology: Learning, Memory, and Cognition. 1990;16:717–726. doi: 10.1037//0278-7393.16.4.717. [DOI] [PubMed] [Google Scholar]
  12. Ellis RJ, Langford TD, Masliah E. HIV and antiretroviral therapy in the brain: Synaptodendritic injury and repair. Nature Reviews Neuroscience. 2007;8:33–44. doi: 10.1038/nrn2040. [DOI] [PubMed] [Google Scholar]
  13. Erdfelder E, Faul F, Buchner A. G*Power: A general power analysis program. Behavior Research Methods, Instruments, & Computers. 1996;28:1–11. [Google Scholar]
  14. Hannon R, Adams P, Harrington S, Fries-Dias C, Gipson MT. Effects of brain injury and age on prospective memory self-rating and performance. Rehabilitation Psychology. 1995;40:289–298. [Google Scholar]
  15. Hedges LV, Olkin I. Statistical methods for meta-analysis. New York: Academic Press; 1985. [Google Scholar]
  16. Henderson M, Safa F, Easterbrook P, Hotopf M. Fatigue among HIV-infected patients in the era of highly active antiretroviral therapy. HIV Medicine. 2005;6:347–352. doi: 10.1111/j.1468-1293.2005.00319.x. [DOI] [PubMed] [Google Scholar]
  17. Hinkin CH, van Gorp WG, Satz P, Marcotte T, Durvasula RS, Wood S, et al. Actual versus self-reported cognitive dysfunction in HIV-1 infection: Memory-metamemory dissociation. Journal of Clinical and Experimental Neuropsychology. 1996;18:431–443. doi: 10.1080/01688639608408999. [DOI] [PubMed] [Google Scholar]
  18. Knight RG, Harnett M, Titov N. The effects of traumatic brain injury on the predicted and actual performance of a test of prospective remembering. Brain Injury. 2005;19:19–27. doi: 10.1080/02699050410001720022. [DOI] [PubMed] [Google Scholar]
  19. Maj M, Satz P, Janssen R, Zaudig M, Starace F, D’Elia L, et al. WHO Neuropsychiatric AIDS study, cross-sectional phase II. Neuropsychological and neurological findings. Archives of General Psychiatry. 1994;51:51–61. doi: 10.1001/archpsyc.1994.03950010051007. [DOI] [PubMed] [Google Scholar]
  20. Martin EM, Nixon H, Pitrak DL, Weddington W, Rains NA, Nunnally G, et al. Characteristics of prospective memory deficits in HIV-seropositive substance dependent individuals: Preliminary observations. Journal of Clinical and Experimental Neuropsychology. doi: 10.1080/13803390600800970. in press. [DOI] [PubMed] [Google Scholar]
  21. McDaniel MA, Guynn MJ, Einstein GO, Breneiser J. Cue-focused and reflexive-associative processes in prospective memory. Journal of Experimental Psychology: Learning, Memory, and Cognition. 2004;30:605–614. doi: 10.1037/0278-7393.30.3.605. [DOI] [PubMed] [Google Scholar]
  22. McNair DM, Lorr M, Droppleman LF. Manual for the profile of mood states. San Diego: Educational and Industrial Testing Service; 1981. [Google Scholar]
  23. Middleton LS, Denney DR, Lynch SG, Parmenter B. The relationship between perceived and objective cognitive functioning in multiple sclerosis. Archives of Clinical Neuropsychology. 2006;21:487–494. doi: 10.1016/j.acn.2006.06.008. [DOI] [PubMed] [Google Scholar]
  24. Millikin CP, Rourke SB, Halman MH, Power C. Fatigue in HIV/AIDS is associated with depression and subjective neurocognitive complaints but not neuropsychological functioning. Journal of Clinical and Experimental Neuropsychology. 2003;25:201–215. doi: 10.1076/jcen.25.2.201.13644. [DOI] [PubMed] [Google Scholar]
  25. Park DC, Kidder DP. Prospective memory and medication adherence. In: Brandimonte M, Einstein GO, McDaniel MA, editors. Prospective memory: Theory and applications. Mahwah, NJ: Erlbaum; 1996. pp. 369–390. [Google Scholar]
  26. Petrides M, Milner B. Deficits on subject-ordered tasks after frontal and temporal lobe lesions in man. Neuropsychologia. 1982;20:249–262. doi: 10.1016/0028-3932(82)90100-2. [DOI] [PubMed] [Google Scholar]
  27. Raskin S. Memory for intentions screening test [abstract] Journal of the International Neuropsychological Society. 2004;10(Suppl 1):110. [Google Scholar]
  28. Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery: Theory and clinical interpretation. 2. Tucson, AZ: Neuropsychology Press; 1985. [Google Scholar]
  29. Rourke SB, Halman MH, Bassel C. Neurocognitive complaints in HIV-infection and their relationship to depressive symptoms and neuropsychological functioning. Journal of Clinical and Experimental Neuropsychology. 1999a;21:737–756. doi: 10.1076/jcen.21.6.737.863. [DOI] [PubMed] [Google Scholar]
  30. Rourke SB, Halman MH, Bassel C. Neuropsychiatric correlates of memory – metamemory dissociations in HIV-infection. Journal of Clinical and Experimental Neuropsychology. 1999b;21:757–768. doi: 10.1076/jcen.21.6.757.852. [DOI] [PubMed] [Google Scholar]
  31. Smith GV, Della Sala S, Logie RH, Maylor EA. Prospective and retrospective memory in normal ageing and dementia: A questionnaire study. Memory. 2000;8:311–321. doi: 10.1080/09658210050117735. [DOI] [PubMed] [Google Scholar]
  32. Stern Y, Marder K, Bell K, Chen J, Dooneief G, Goldstein S, et al. Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. Archives of General Psychiatry. 1991;48:131–138. doi: 10.1001/archpsyc.1991.01810260039006. [DOI] [PubMed] [Google Scholar]
  33. van Gorp WG, Satz P, Hinkin C, Selnes O, Miller EN, McArthur J, et al. Metacognition in HIV-1 seropositive asymptomatic individuals: Self-ratings versus objective neuropsychological performance. Multicenter AIDS Cohort Study (MACS) Journal of Clinical and Experimental Neuropsychology. 1991;13:812–819. doi: 10.1080/01688639108401091. [DOI] [PubMed] [Google Scholar]
  34. Wilson BA, Emslie H, Foley J, Shiel A, Watson P, Hawkins K, et al. Cambridge Test of Prospective Memory (CAMPROMPT) San Antonio, TX: Harcourt Assessment; 2005. [Google Scholar]
  35. Woods SP, Morgan EE, Marquie-Beck J, Carey CL, Grant I, Letendre SL, et al. Markers of macrophage activation and axonal injury are associated with prospective memory in HIV-1 disease. Cognitive and Behavioral Neurology. 2006;19:217–221. doi: 10.1097/01.wnn.0000213916.10514.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Woods SP, Twamley EW, Dawson MS, Narvaez JM, Jeste DV. Deficits in cue detection and intention retrieval underlie prospective memory impairment in schizophrenia. Schizophrenia Research. doi: 10.1016/j.schres.2006.11.005. in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. World Health Organization. Composite international diagnostic interview. CIDI, version 2.1. Geneva, Switzerland: World Health Organization; 1998. [Google Scholar]
  38. Zeintl M, Kliegel M, Rast P, Zimprich D. Prospective memory complaints can be predicted by prospective memory performance in older adults. Dementia and Geriatric Cognitive Disorders. 2006;22:209–215. doi: 10.1159/000094915. [DOI] [PubMed] [Google Scholar]

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