Executive functioning impairment in women treated with chemotherapy for breast cancer: a systematic review.

PURPOSE: Women with breast cancer have reported adverse cognitive effects following chemotherapy. Evidence is mixed on whether executive functioning is particularly impaired in women treated with chemotherapy, in part due to the wide range of tasks used to measure executive processes. We performed a systematic review of the published literature to evaluate whether some subcomponents of executive functioning are more vulnerable to impairment than others among breast cancer survivors who had been treated with chemotherapy. METHODS: Studies published as of April 2017 were identified using three electronic databases (MEDLINE, PsycINFO, and Web of Science) and a manual search of relevant reference lists. The methodological quality of included studies was assessed using a checklist of predefined criteria. RESULTS: Of 1280 identified articles, a total of 41 were included for review. Study findings were categorized into three primary subdomains of executive functioning: inhibition, shifting, and updating. Although there was heterogeneity in the neuropsychological measures used to assess executive functioning, tests could be grouped into the subcomponents they assessed. Inhibition appears relatively spared from the effects of chemotherapy, whereas impairments in shifting and updating are more commonly found following chemotherapy. CONCLUSIONS: Examination of subcomponents of executive functioning is recommended to better characterize the nature of executive dysfunction in women treated with chemotherapy. Future studies should include executive functioning tasks of varying complexity, use of multiple tasks to increase reliability, and alternative indices to capture performance, such as within-person variability.

Intraindividual variability in reaction time before and after neoadjuvant chemotherapy in women diagnosed with breast cancer.

OBJECTIVE: Women treated with chemotherapy for breast cancer experience subtle cognitive deficits. Research has focused on mean performance level, yet recent work suggests that within-person variability in reaction time performance may underlie cognitive symptoms. We examined intraindividual variability (IIV) in women diagnosed with breast cancer and treated with neoadjuvant chemotherapy. METHODS: Patients (n = 28) were assessed at baseline before chemotherapy (T1), approximately 1 month after chemotherapy but prior to surgery (T2), and after surgery about 9 months post chemotherapy (T3). Healthy women of similar age and education (n = 20) were assessed at comparable time intervals. Using a standardized regression-based approach, we examined changes in mean performance level and IIV (eg, intraindividual standard deviation) on a Stroop task and self-report measures of cognitive function from T1 to T2 and T1 to T3. RESULTS: At T1, women with breast cancer were more variable than controls as task complexity increased. Change scores from T1 to T2 were similar between groups on all Stroop performance measures. From T1 to T3, controls improved more than women with breast cancer. IIV was more sensitive than mean reaction time in capturing group differences. Additional analyses showed increased cognitive symptoms reported by women with breast cancer from T1 to T3. Specifically, change in language symptoms was positively correlated with change in variability. CONCLUSIONS: Women with breast cancer declined in attention and inhibitory control relative to pretreatment performance. Future studies should include measures of variability, because they are an important sensitive indicator of change in cognitive function.

Pretreatment Differences in Intraindividual Variability in Reaction Time between Women Diagnosed with Breast Cancer and Healthy Controls.

OBJECTIVES: Chemotherapy has adverse effects on cognitive performance in women treated for breast cancer, but less is known about the period before chemotherapy. Studies have focused on mean level of performance, yet there is increasing recognition that variability in performance within an individual is also an important behavioral indicator of cognitive functioning and underlying neural integrity. METHODS: We examined intraindividual variability (IIV) before chemotherapy and surgery in women diagnosed with breast cancer (n=31), and a healthy control group matched on age and education (n=25). IIV was calculated across trials of a computerized Stroop task, including an examination of the slowest and fastest trials of reaction time (RT) responses. RESULTS: The groups were equivalent on overall accuracy and speed, and participants in both groups were less accurate and slower on incongruent trials compared with congruent trials. However, women with breast cancer became more variable with increased task difficulty relative to healthy controls. Among the slowest RT responses, women with breast cancer were significantly more variable than healthy controls on incongruent trials. This suggests that a specific variability-producing process (e.g., attentional lapses) occurs in task conditions that require executive control (e.g., incongruent trials). CONCLUSIONS: Results are consistent with other evidence of executive dysfunction among women treated for breast cancer. These findings highlight the importance of pretreatment assessment and show that variability in performance provides information about cognition that measures of central tendency do not.

Long-term maintenance of smartphone and PDA use in individuals with moderate to severe memory impairment.

In an earlier paper we described a structured, theory-driven training programme which was administered to 10 individuals with moderate-to-severe memory impairment. All individuals received an errorless-fading-of-cues protocol in the use of personal digital assistants (PDAs) or smartphones (Svoboda, Richards, Leach, & Mertens, 2012) and demonstrated generalisation of acquired skills to day-to-day memory challenges. Maintenance of intervention gains over the long-term is another indicator of successful generalisation. Here we present the maintenance of device use in the same group of individuals 12 to 19 months after programme completion. A within-subject, ABABB multi-case experimental design was used to evaluate the impact of PDA or smartphone use on day-to-day memory functioning at baseline, immediately post-intervention, at return to baseline, and at short-term and long-term follow-up. Results presented here focus predominantly on long-term follow-up. All 10 individuals showed maintenance of gains in day-to-day functioning as quantified across several ecologically valid questionnaire and task-based measures. This was corroborated by family members with whom six of the participants resided. This study further demonstrates the programme's clinical effectiveness in enabling individuals with moderate-to-severe memory impairment to function more independently and with greater confidence up to 19 months following programme completion.

Selective attrition and intraindividual variability in response time moderate cognitive change.

OBJECTIVES: Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. METHOD: Three hundred and four community dwelling older adults (64-92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. RESULTS: We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to that of individuals who remained in the study. DISCUSSION: These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults.

Lifelong estrogen exposure and memory in older postmenopausal women.

Menopausal changes in endogenous estrogen have been associated with memory decline. However, because earlier findings regarding the effects of lifelong estrogen exposure on memory have been inconsistent, our purpose was to investigate these effects in older postmenopausal women with a comprehensive battery of memory measures. Participants were 126 nondemented naturally postmenopausal women, not currently using hormone therapy (HT), 60 to 89 years of age, who showed normal to below average verbal memory performance on a screening test. Memory measures included tests of visual, verbal, and working memory. Regression analyses were performed with each memory measure as the outcome and length of reproductive period (time between menarche and menopause) as the predictor, controlling for age, education, parity, duration of breastfeeding, previous HT and oral contraceptive use, as well as body mass index and depression. Longer reproductive period was significantly associated with better delayed visual memory, immediate and delayed verbal memory, and working memory. Previous HT use was also significantly associated with better verbal memory and delayed visual memory. Our findings suggest an enduring protective role of endogenous and exogenous estrogen on memory in older postmenopausal women with normal to below average verbal memory performance on a screening test. They also support our contention that the neuroprotective benefits of a longer reproductive period might only be evident after a longer period of postmenopausal estrogen deprivation, which would help clarify why such an association was not previously found in younger postmenopausal women. Replication is required with a larger sample representing a broader cross-section of the aging female population.

Neuropsychological tests accurately predict incident Alzheimer disease after 5 and 10 years.

OBJECTIVE: To determine whether neuropsychological tests accurately predict incident Alzheimer disease (AD) after 5 and 10 years in participants of the Canadian Study of Health and Aging (CSHA) who were initially nondemented. METHODS: The CSHA was conducted in three waves: CSHA-1 (1991 to 1992), CSHA-2 (1996 to 1997), and CSHA-3 (2001 to 2002). The 10-year prediction study included those who completed neuropsychological testing at CSHA-1 and received a diagnostic assessment at CSHA-3 (n = 263). The 5-year prediction study included those who completed neuropsychological testing at CSHA-2 and received a diagnostic assessment at CSHA-3 (n = 551). The diagnostic workup for dementia at CSHA-3 was formulated without knowledge of neuropsychological test performance at CSHA-1 or CSHA-2. The authors excluded cases with a baseline diagnosis of dementia or a prior history of any condition likely to affect the brain. Age and education were included in all analyses as covariates. RESULTS: In the 10-year follow-up study, only one test (short delayed verbal recall) emerged from the forward regression analyses. The model with this test and two covariates was significant, chi2 (3) = 31.61, p < 0.0001 (sensitivity = 73%, specificity = 70%). In the 5-year follow-up study, three tests (short delayed verbal recall, animal fluency, and information) emerged from the forward logistic regression analyses. The model was significant, chi2 (5) = 91.34, p < 0.0001 (sensitivity = 74%, specificity = 83%). Both models were supported with bootstrapping estimates. CONCLUSIONS: In a large epidemiologic sample of nondemented participants, neuropsychological tests accurately predicted conversion to Alzheimer disease after 5 and 10 years.