The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors.

PURPOSE: This study aims to determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance but that smoking history would decrease the negative effect of ε4 on cognition. METHODS: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 328) and age and education matched non-cancer controls (N = 162) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected, and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. RESULTS: After adjusting for age, cognitive reserve, depression, and fatigue, breast cancer survivors scored significantly lower on all domains of cognitive function. A significant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A significant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. CONCLUSIONS: The results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors, and disease history in determining cognitive function. IMPLICATIONS FOR CANCER SURVIVORS: These results help explain why only a subset of breast cancer survivors appear to be vulnerable to cognitive problems.

Initial encoding deficits with intact memory retention in older long-term breast cancer survivors.

PURPOSE: Cancer survivors frequently report significant forgetfulness, but standard neuropsychological tests often fail to detect primary memory deficits. Past research has suggested survivors may misattribute forgetfulness to memory decay rather than impairments in initial encoding, but no studies have tested whether this pattern is evident in older survivors, who are more vulnerable to age-related memory difficulties. We examined whether long-term breast cancer survivors treated in older adulthood demonstrate deficits in initial encoding, as opposed to increased rates of memory decay, relative to non-cancer controls. METHODS: Three hundred twenty-eight breast cancer survivors age 60 and above, 5-15 years post-treatment, and 162 age-matched non-cancer controls completed list learning and narrative memory assessments at four time-points over 2 years. Performance on learning trials and delayed recall was analyzed at each time-point to assess group differences in memory encoding, and memory decay was assessed by analyzing changes in performance across delays. RESULTS: Univariate ANCOVAs correcting for age and education showed that survivors had worse initial encoding performance across multiple time-points, which were compensated for with multiple learning trials to produce recall performance comparable to controls. There were no significant group differences in memory decay. CONCLUSIONS: Older long-term breast cancer survivors exhibit a consistent pattern of initial encoding deficits, but memory retention was comparable to controls. Future research should consider the role of encoding deficits and age-related factors when evaluating cognitive function in older survivors. IMPLICATIONS FOR CANCER SURVIVORS: Commonly reported memory problems may stem from encoding deficits in older long-term cancer survivors.

Relationship between cognitive functioning and frailty in older breast cancer survivors.

INTRODUCTION: The relationship between cognitive function and frailty in older, long-term breast cancer survivors was examined. MATERIALS AND METHODS: Breast cancer survivors who were diagnosed and treated at 60 years of age or above and were 5-15 year disease-free survivors and non-cancer controls matched on age and education were evaluated with neuropsychological tests and the Comprehensive Geriatric Assessment which was used to assess frailty based on a deficit accumulation frailty index (DAFI). RESULTS: Unadjusted regression analyses revealed that cancer survivors scored significantly lower on the Language (P = 0.015), Attention, Processing Speed, Executive Function (APE) (P = 0.015), and Learning and Memory (LM) (P = 0.023) domains compared to controls. However, only the LM domain remained significantly different (P = 0.002) in the adjusted analysis. Survivors had significantly higher DAFI scores compared to controls (p = 0.006) and significantly more survivors were categorized as pre-frail or frail (35%) compared to controls (23%, P = 0.009). Increasing frailty scores were associated with worse cognitive performance across all domains (all Ps ≤ 0.004). For the LM domain, there was a significant interaction (P = 0.019) between DAFI score and survivorship vs control status. Survivors demonstrated a significant linear decline in LM scores as DAFI scores increased, whereas controls demonstrated comparable scores between the robust and pre-frail DAFI groups, demonstrating decline in the frailty group only. CONCLUSION: Older, long-term breast cancer survivors had lower cognitive performance and higher levels of frailty compared to controls. For the Learning and Memory domain, the decline in performance began in the pre-frail range for survivors, but not controls.

Impact of transcranial direct current stimulation on sustained attention in breast cancer survivors: Evidence for feasibility, tolerability, and initial efficacy.

BACKGROUND: A significant subset of breast cancer survivors experience cognitive difficulties in attention and memory, which persist for years following treatment. Transcranial direct current stimulation (tDCS) has been shown to be effective in improving working memory, attention, processing speed, and other cognitive functions in both healthy and clinical populations. To date, no studies have examined tDCS for rehabilitation of cancer-related cognitive dysfunction. OBJECTIVE/HYPOTHESIS: We aimed to provide preliminary evidence for feasibility, tolerability, acceptability, and efficacy of tDCS in improving performance on a measure of sustained attention. METHODS: In a within-subjects design, 16 breast cancer survivors underwent 2 consecutive days of active tDCS over the prefrontal cortex, and 2 days of sham tDCS, counterbalanced for order of stimulation condition, while performing a continuous performance test. RESULTS: Stimulation was feasible and tolerable, with 89% of participants completing all sessions, and none reporting more than mild to moderate discomfort. Analyses of efficacy showed that during active stimulation, participants had significantly lower standard errors of reaction times overall, indicating better sustained attention ability, as compared to sham stimulation (p < 0.05). Furthermore, the effect of stimulation on standard errors of reaction times differed by inter-stimulus interval (ISI): for 1 and 2 s ISIs, there was no significant difference in performance between sham and active tDCS conditions, but for 4 s ISIs, stimulation improved variability in response times relative to sham (p < 0.05). CONCLUSIONS: Results suggest that tDCS is feasible, tolerable, and may be an effective intervention to improve sustained attention difficulties in survivors with cancer-related cognitive dysfunction.