Response inhibition and everyday memory complaints in older adult women

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2006; 21: 1115 1120. Published online 5 September 2006 in Wiley InterScience (www.interscience.wiley.com).1615 Response inhibition and everyday memory complaints in older adult women Guy G. Potter 1 * and Marilyn Hartman 2 1 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA 2 Department of Psychology, University of North Carolina at Chapel Hill, NC, USA SUMMARY Objective To explore the association of executive functions to the everyday memory complaints of healthy older adults. Methods Ninety-nine community-dwelling women aged 60 and above were administered a battery that included neuropsychological tests of executive functions and memory, along with self-report measures of everyday memory complaints, depression, and anxiety. Results Multivariate regression analyses revealed that a measure of response inhibition (Stroop Color-Word) accounted for unique variance in predicting memory complaints above and beyond measures of episodic memory, depression, and anxiety. Depression, however, accounted for the largest variance in memory complaints. Conclusions Higher frequency of everyday memory complaints among older adults was associated with decreased response inhibition independent of episodic memory and affective state. Further research is needed to understand the interrelationships among these and other predictors of everyday memory complaints. Copyright # 2006 John Wiley & Sons, Ltd. key words memory complaints; executive functions; response inhibition; Stroop Test; depression; elderly INTRODUCTION Although forgetfulness in everyday activities is a common complaint of older adults (Kausler, 1991), research showing a relationship between memory complaints and later dementia (Jonker et al., 2000) suggests it is also an important clinical issue. The significance of memory complaints is difficult to appraise, however, because they have an inconsistent relationship to episodic memory performance (e.g. Zelinski et al., 1990; Hänninen et al., 1994). For instance, whereas some studies have found a significant association using a measure of text recall (Cavanaugh and Poon, 1989), others have found significant results for word recall but not text recall (Zelinski et al., 1990), and still others have found no association for either measure (Derouesné et al., *Correspondence to: G. G. Potter, Duke University Program in Epidemiology of Dementia, 905 W. Main St., Box 41/Suite 25-D, Durham, NC 27701, USA. E-mail: guy.potter@duke.edu Copyright # 2006 John Wiley & Sons, Ltd. 1999). When significant effects do occur, they are often small to moderate. A number of factors may contribute to these findings, including variability in measures used to assess memory complaints; differences among clinical, community, and laboratorybased sample populations; and differential attention to the contribution of depressive symptomatology (Jonker et al., 2000). An additional factor may be that individual perceptions of memory failure do not necessarily differentiate episodic memory from other neurocognitive processes, such as executive functions (Howieson and Lezak, 1995). Many everyday incidents of forgetfulness that contribute to memory complaints among older adults occur in an environment characterized by taskirrelevant distractions and competing demands for cognitive resources (Rabbit and Abson, 1990), the management of which requires executive functions, those pre-frontally mediated processes, such as selective attention, response inhibition, and working memory, that perform the role of organizing behavior Received 19 August 2005 Accepted 20 March 2006

1116 g. g. potter and m. hartman in a complex environment (Baddeley, 1986; Norman and Shallice, 1986). Executive functions are associated with memory complaints among individuals with multiple sclerosis (Randolph et al., 2004), and with metamemory inaccuracy among individuals with HIV infection (Rourke et al., 1999). The association between executive functions and memory complaints has not been specifically examined in older adults, however, despite findings that executive functions become less efficient with age (West et al., 2002) and may contribute to reduced episodic memory performance (Stuss et al., 1996). The primary hypothesis of this study was that poorer performance by older adults on clinical tests of executive functions would be associated with higher levels of everyday memory complaints, independent of performance on clinical tests of episodic memory. In addition, we controlled for the effects of depression, which is often a better predictor of memory complaints among healthy elderly than episodic memory (Levy-Cushman and Abeles, 1998). Similarly, we controlled for anxiety because it also appears to elevate memory complaints in healthy community populations (Jonker et al., 1997). The current study was limited to women in order to avoid potential gender confounds (Crook et al., 1992; Gagnon et al., 1994). For instance, women report more memory complaints (Cutler and Grams, 1988), have higher prevalence of depression (American Psychiatric Association, 1994), and are at slightly greater risk for Alzheimer s disease (Bondi et al., 1992). METHODS Participants Participants (n ¼ 99) were community-dwelling women aged 60 and older (M ¼ 72.9 years, SD ¼ 7.4, range ¼ 60 89) screened for neurological conditions, uncontrolled hypertension, psychiatric hospitalization (within 5 years), current psychoactive medication, and dementia, based on the Mini Mental State Exam (MMSE, Folstein et al., 2001, scores 24; mean ¼ 29.14, SD ¼ 1.03, range ¼ 25 30). Mean education was 16.1 years (SD ¼ 2.3, range ¼ 9 20). Measures Memory complaints were assessed with the General Frequency of Forgetting (GFF) scale from the Memory Functioning Questionnaire (MFQ; Gilewski et al., 1990). Forgetfulness for names, appointments and other everyday information was rated on a seven-point Likert-type scale, with lower scores indicating greater levels of complaint. The 33-items of the GFF subscale account for the largest amount of variance on the MFQ and are most consistently associated with episodic memory performance (Gilewski et al., 1990). Executive functions The Color-Word condition of the Stroop Color and Word Test (Stroop-CW; Golden, 1978). This assesses selective attention and response inhibition (Shum et al., 1990). Participants read color words (red, green, and blue) printed in an incongruent ink color (e.g. green printed in red ink). The score was correct responses within 45 sec. Trail Making Test (Reitan, 1992). Part A (TMT-A) assesses controlled attention, while Part B (TMT-B) adds the executive demand of set shifting (Shum et al., 1990; Felmingham et al., 2004). On TMT-A, participants connect circles numbered 1 25 in order; on TMT-B, circles must be connected by alternating between numbers and letters (e.g. 1 A, 2 B, etc.). The score was time to completion, with lower scores indicating better performances. The Letter-Number Sequencing (LNS) subtest of the Wechsler Memory Scale 3rd Edition, (WMS-III; Wechsler, 1997). This assesses the capacity to simultaneously store and reorganize information in working memory. Participants hear a series of numbers and letters, then repeat the series with numbers in ascending order, followed by letters in alphabetic order. The score was number of sequences correctly repeated. The Paced Auditory Serial Addition Test (PASAT; Gronwall, 1977). This assesses the executive ability to update the contents of working memory. Participants hear a series of audiotaped digits and respond continually with the sum of the two that were most recently presented. The score was the number of correct responses on Trial 1. Episodic memory Logical Memory I and II of the WMS-III (LM I, LM II, Wechsler, 1997). This assesses immediate (LM I) and delayed (LM II) recall for prose passages. The score for each part was the total number of words recalled.

response inhibition and everyday memory complaints 1117 Word Lists I and II of the WMS-III (WL I, WL II, Wechsler, 1997). This assesses immediate (WL I) and delayed (WL II) recall of word lists. The score for each part was the total number of words recalled. Depression and anxiety The Geriatric Depression Scale (GDS; Yesavage et al., 1983). This is a 30-item self-report inventory developed and validated in an older adult population. The Beck Anxiety Inventory (BAI; Beck and Steer, 1990) is a 21-item self-report questionnaire of anxiety-related symptomatology. Procedure After informed consent, participants were tested individually by trained examiners. Table 1. Descriptive statistics for memory complaints and independent variables n Mean SD Range Memory complaints General frequency of forgetting 99 169.61 21.06 100 214 Neuropsychological measures Stroop Color-Word 99 36.51 8.18 17 55 Trail Making Test (Part A) 99 33.81 12.59 15 89 Trail Making Test (Part B) 98 86.69 40.87 36 237 Letter-Number Sequencing 99 10.86 2.30 6 18 PASAT (Trial 1) 93 32.65 10.47 12 49 Logical Memory I 98 43.45 8.47 23 62 Logical Memory II 99 27.91 7.21 5 41 Word Lists I 99 32.46 5.21 20 45 Word Lists II 99 7.10 2.74 0 12 Affective status variables Geriatric Depression Scale 97 4.08 3.46 0 13 Beck Anxiety Inventory 99 2.97 3.28 0 13 Variation in n among individual measures reflects non-completion of those tests by individual participants. Statistical methods In addition to univariate and bivariate descriptive analyses, candidate measures of executive functions and memory were selected for inclusion in the full predictive model using separate simultaneous regression procedures (backward elimination, p < 0.05), with memory complaints as the dependent variable. We then regressed memory complaints on the selected variables in hierarchical order: (1) depression and anxiety, (2) memory, and (3) executive functions. Significance tests after steps 2 and 3 assessed whether entry of memory and executive functions added to the predictive ability of the model. RESULTS Descriptive statistics appear in Table 1. Correlations among neuropsychological measures appear in Table 2. There were significant, moderate correlations among executive function measures (median r 2 ¼ 0.42), lowto-moderate correlations among most measures of episodic memory (median r 2 ¼ 0.30), and an inconsistent pattern of correlations across these two domains. Although affective measures were not significantly correlated with any neuropsychological measures (Table 3), trends existed between GDS and TMT-A (p ¼ 0.07) and Stroop-CW (p ¼ 0.06). Higher levels of memory complaints were significantly associated with poorer performances on three executive function tests (Stroop-CW, TMT-A, and LNS), and on three tests of episodic memory (LM I, LM II, and WL II). Higher levels of memory complaints were associated with higher levels of both depression and anxiety (Table 3). Multivariate analyses Backward elimination of executive function variables predicting memory complaints [F(1,91) ¼ 14.14, MSE ¼ 378.59, p ¼ 0.02] was significant only for Stroop-CW (b ¼ 0.61, SE ¼ 0.25, p ¼ 0.02). An analogous elimination procedure for memory variables was significant overall [F(3, 94) ¼ 6.32, MSE ¼ 2409.46, p ¼ 0.0006] and for three memory measures: (1) WL I (b ¼ 1.07, SE ¼ 0.53, p ¼ 0.04), WL II (b ¼ 3.86, SE ¼ 1.21, p ¼ 0.0009), and LM I (b ¼ 0.65, SE ¼ 0.25, p ¼ 0.01). In hierarchical regression analyses (Table 4), all three models significantly predicted memory complaints: Step 1 with depression and anxiety [F(2, 94) ¼ 16.16, MSE ¼ 340.53, p ¼ < 0.0001], Step 2 with memory added [F(5, 91) ¼ 10.41, MSE ¼ 300.74, p < 0.0001), and Step 3 with executive function added (Stroop-CW) [F(6, 90) ¼ 9.75, MSE ¼ 289.69, p < 0.0001]. The final model with Stroop-CW was statistically significant, along with GDS, BAI, WL I, and LM I; however, the effect of WL I was in the opposite direction of LM 1 and Stroop-CW. Examining the increase in variance across all three models indicates that the addition of memory in Step 2 significantly increased the variance attributable to the model from 25.6% to 36.4% (p ¼ 0.003). Addition of Stroop-CW in Step 3 led to a further significant

1118 g. g. potter and m. hartman Table 2. Correlations among measures of executive functions, memory, and affective status STR-CW TMT-A TMT-B LNS PASAT LM I LM II WL I WL II GDS TMT-A 0.42** TMT-B 0.40** 0.68** LNS 0.30** 0.38** 0.46** PASAT 0.49** 0.42** 0.48** 0.42** LM I 0.18 0.28** 0.23* 0.19 0.20 LM II 0.19 0.26** 0.19 0.16 0.21* 0.90** WL I 0.44** 0.26** 0.49** 0.40** 0.42** 0.31** 0.28** WL II 0.37** 0.31** 0.37** 0.31** 0.15 0.16 0.23* 0.66** GDS 0.18 0.19 0.08 0.08 0.01 0.04 0.05 < 0.01 0.14 BAI 0.04 0.07 < 0.01 0.08 0.06 0.04 0.01 0.10 0.14 0.33** *p < 0.05. **p < 0.01. STR-CW ¼ Stroop Color-Word; LNS ¼ Letter-Number Sequencing; TMT-A ¼Trail Making Test, Part A; TMT-B ¼ Trail Making Test, Part B; WL I ¼ Word Lists I, WL II ¼ Word Lists II; LM I ¼ Logical Memory I; LM II ¼ Logical Memory II; GDS ¼ Geriatric Depression Scale; BAI ¼ Beck Anxiety Inventory. increase in the variance attributable to the model, to 39.4% (p ¼ 0.04). DISCUSSION This study found that decreased response inhibition, as assessed by Stroop-CW, was associated with more frequent memory complaints among older adult women, even after accounting for episodic memory performance, depression, and anxiety. Other measures assessing executive functions were not significantly associated with memory complaints in multivariate models. Our findings suggest that some of the occurrences that older adults report as memory failures, such as forgetting phone numbers or misplacing objects, may reflect difficulty inhibiting interference from irrelevant information. Because not all measures of executive functions were associated with memory complaints, we conducted a post-hoc factor analysis to determine how well these executive function measures reflected our construct. This analysis produced a single factor with item loadings ranging from 0.65 to 0.82, but a factor score variable derived from this analysis was not associated with memory complaints. Thus, while our measures do appear to reflect an underlying construct Table 3. Correlation of memory complaints and independent variables with age and education GFF Age Education MMSE Memory complaints General Frequency of Forgetting 0.09 0.06 0.06 Affective status Geriatric Depression Scale 0.47** 0.20* 0.01 0.12 Beck Anxiety Inventory 0.32** 0.02 0.01 0.01 Executive function Stroop Color-Word 0. 31** 0.34** 0.06 0.26* Trail Making Test (Part A) 0.33** 0.39** 0.05 0.32** Trail Making Test (Part B) 0.13 0.36** 0.22* 0.35** Letter-Number Sequencing 0.20* 0.11 0.21* 0.22* PASAT 0.13 0.29** 0.11 0.26* Episodic memory Logical Memory I 0.25* 0.16 0.24* 0.17 Logical Memory II 0.21* 0.10 0.18 0.23* Word Lists I 0.11 0.34** 0.05 0.28* Word Lists II 0.29** 0.26* 0.03 0.12 *p < 0.05. **p < 0.01.

response inhibition and everyday memory complaints 1119 Hierarchical regression models predicting memory com- Table 4. plaints Variable b SE t p Model R 2 Step 1 GDS 2.51 0.58 4.35 <0.0001 BAI 1.21 0.61 2.00 0.048 Step 2 GDS 2.20 0.55 3.98 0.0001 BAI 1.12 0.57 1.95 0.05 Word Lists-I 0.84 0.48 1.76 0.08 Word Lists-II 2.93 1.02 2.87 0.005 LM-I 0.59 0.22 2.69 0.009 Step 3 GDS 1.97 0.55 3.58 <0.0006 BAI 1.20 0.56 2.13 0.04 Word Lists-I 1.12 0.49 2.30 0.02 Word Lists-II 2.71 1.01 2.69 0.01 LM-I 0.57 0.22 2.64 0.01 Stroop-CW 0.51 0.24 2.11 0.04 0.26 0.36 0.39 GDS ¼ Geriatric Depression Scale; BAI ¼ Beck Anxiety Inventory; LM-I ¼ Logical Memory I; LM-II ¼ Logical Memory II; Stroop- CW ¼ Stroop Color-Word. of executive functions, what appears to be more important is how the characteristics of individual measures- specifically response inhibition- are related to memory complaints. The current study also supported previous laboratory and population-based studies showing an association between episodic memory and memory complaints (Zelinski et al., 1990; Gagnon et al., 1994), finding significant relationships with both word lists and text recall. An unexpected finding, however, was that one measure of word list recall (WL I) was not significantly associated with memory complaints in bivariate analysis, but was significant in multivariate models in the opposite direction from the other two memory measures. This inconsistency is likely due to the effects of intercorrelated neuropsychological measures competing to predict variance in memory complaints. Although further differentiating these effects is beyond the scope of this study, there may be complex relationships among memory complaints and memory based on mode of presentation (lists vs prose), delay interval, or both. Consistent with previous research, depressive symptomatology accounted for a significant proportion of variance (McGlone et al., 1990; Levy- Cushman and Abeles, 1998) in memory complaints. Anxiety also accounted for unique variance in the full model. Although symptomatology of depression and anxiety in the current study were minimal by clinical standards, the trends toward significant associations between depression and some measures of executive functions suggest that mediating or moderating effects of affective status may be more evident in clinical populations. Even in the current sample, however, it is possible that depression and anxiety represent a cognitive bias toward negative attributions (Beck, 1995). This type of bias was related to higher levels of memory complaints in a study of chronic pain patients (Muñoz and Esteve, 2005). It should be noted that the current results were based on a sample of women free of major psychiatric and medical problems, and who were largely college educated. Although this approach minimized confounds to interpreting memory complaints, it will be important to determine whether the current findings apply to men, to those with less education, and to those with psychiatric and medical diagnoses. In summary, it appears that multiple factors contribute to memory complaints in communitydwelling elders, including response inhibition, memory, anxiety, and depression. Consequently, it is important for clinicians and researchers alike to consider that there may be multiple etiologies for these complaints. ACKNOWLEDGMENTS The authors wish to thank: Joshua Martin for his valuable work on this study; Mareah Steketee, Laura Clark, Ute Bayen, and Jack Vevea for their scientific and editorial input; and Carol Woods Retirement Community, the Forest at Duke, and the Chapel Hill Senior Center for their generous assistance. This work was supported in part by a small project grant from the University of North Carolina Institute on Aging. REFERENCES American Psychiatric Association. 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC. Baddeley AD. 1986. Working memory. Oxford University Press: Oxford. Beck JS. 1995. Cognitive Therapy: Basics and Beyond. Guilford Press: New York. Beck AT, Steer RA. 1990. Manual for the Beck Anxiety Inventory. The Psychological Corporation: San Antonio, TX. Bondi MW, Salmon DP, Kaszniak AW. 1992. The neuropsychology of dementia. In europsychological Assessment of Neuropsychiatric Disorders, 2nd edn, Grant I, Adams KM (eds). Oxford University Press: New York; 164 199. Cavanaugh JC, Poon LW. 1989. Metamemorial predictors of memory performance in young and older adults. Psychol Aging 4: 365 368.

1120 g. g. potter and m. hartman Crook TH, Feher EP, Larrabee GJ. 1992. Assessment of memory complaint in Age-Associated Memory Impairment: The MAC-Q. Int Psychogeriatr 4: 165 176. Cutler SJ, Grams AE. 1988. Correlates of self-reported everyday memory problems. J Gerontol 43: S82 S90. Derouesné C, Lacomblez L, Thibault S, et al. 1999. Memory complaints in young and elderly subjects. Int J Geriatr Psychiatry 14: 281 301. Felmingham KL, Baguley IJ, Green AM. 2004. Effects of diffuse axonal injury on speed of information processing following severe traumatic brain injury. Neuropsychology 18: 564 571. Folstein MF, Folstein SE, Fanjiang G. 2001. Mini-Mental State Examination: Clinical Guide and User s Guide. Psychological Assessment Resources: Lutz, FL. Gagnon M, Dartigues JF, Mazaux JM, et al. 1994. Self-reported memory complaints and memory performance in elderly French community residents: results of the PAQUID research program. Neuroepidemiology 13: 145 154. Gilewski MJ, Zelinski EM, Schaie KW. 1990. The Memory Functioning Questionnaire for assessment of memory complaints in adulthood and old age. Psychol Aging 5: 482 490. Golden CJ. 1978. Stroop Color and Word Test. Stoelting: Chicago, IL. Gronwall DMA. 1977. Paced Auditory Serial-Addition Task: a measure of recovery from concussion. Percept Mot Skills 44: 367 373. Howieson DB, Lezak MD. 1995. Separating memory from other cognitive problems. In Handbook of Memory Disorders, Baddeley AD, Wilson BA (eds). John Wiley & Sons: Chichester; 411 426. Hänninen T, Reinikainen K, Helkala E, et al. 1994. Subjective memory complaints and personality traits in normal elderly subjects. J Am Geriatr Soc 42: 1 4. Jonker C, Smits C, Deeg D. 1997. Affect-related metamemory and memory performance in a population-based sample of older adults. Educational Gerontology 23: 115 128. Jonker C, Geerlings MI, Schmand B. 2000. Are memory complaints predictive for dementia? A review of clinical and populationbased studies. Int J Geriatr Psychiatry 15: 983 991. Kausler DH. 1991. Experimental Psychology, Cognition, and Human Aging, 2nd edn. Springer-Verlag: New York. Levy-Cushman J, Abeles N. 1998. Memory complaints in the able elderly. Clin Gerontol 19: 3 24. McGlone J, Gupta S, Humphrey D, et al. 1990. Screening for early dementia using memory complaints from patients and relatives. Arch Neurology 47: 1189 1193. Muñoz M, Esteve R. 2005. Reports of memory functioning by patients with chronic pain. Clin J Pain 21: 287 291. Norman DA, Shallice T. 1986. Attention to action: willed and automatic control of behavior. In Consciousness and Self-Regulation, Vol. 4, Davidson RJ, Schwartz GE, Shapiro D (eds). Plenum Press: New York; 1 18. Rabbit P, Abson V. 1990. Lost and found : some logical and methodological limitations of self-report questionnaires as tools to study cognitive ageing. Br J Psychol 81: 1 16. Randolph JJ, Arnett PA, Freske P. 2004. Metamemory in multiple sclerosis: exploring affective and executive contributors. Arch Clinical Neuropsychol 19: 259 279. Reitan RM. 1992. Trail Making Test: Manual for Administration and Scoring. Reitan Neuropsychological Laboratory: Tuscon, AZ. Rourke SB, Halman MH, Bassel C. 1999. Neuropsychiatric correlates of memory-metamemory dissociations in HIV-infection. J Clin Exp Neuropsychol 21: 757 768. Shum DHK, McFarland KA, Bain JD. 1990. Construct validity of eight tests of attention: Comparison of normal and closed head injured samples. Clinical Neuropsychologist 4: 151 162. Stuss DT, Craik FIM, Sayer L, et al. 1996. Comparison of older people and patients with frontal lesions: Evidence from word list learning. Psychol Aging 11: 387 395. Wechsler D. 1997. Wechsler Memory Scale, 3rd edn. The Psychological Corporation: San Antonio, TX. West R, Murphy KJ, Armilio M, et al. 2002. Lapses of intention and performance variability reveal age-related increases in fluctuations of executive control. Brain Cogn 49: 402 419. Yesavage J, Brinks T, Rose T, et al. 1983. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17: 37 49. Zelinski EM, Gilewski MJ, Anthony-Bergstone CR. 1990. Memory Functioning Questionnaire: concurrent validity with memory performance and self-reported memory failures. Psychol Aging 5: 388 399.