Probability of Alzheimer's disease in breast cancer survivors based on gray‐matter structural network efficiency

Kesler, Shelli R.; Rao, Vikram; Ray, William J.; Rao, Arvind

doi:10.1016/j.dadm.2017.10.002

Cited by 32 publications

(24 citation statements)

References 45 publications

(82 reference statements)

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“…15 Furthermore, chemotherapy produces changes in biomarkers 17 and brain structure that mimic aging. [18][19][20][21] Chronologic age and aging phenotypes, such as frailty 22 and/or high comorbidity burden, may be markers for risk of cognitive decline. 3 Genotypes associated with neurodegenerative disease, including polymorphisms in the apolipoprotein E (ApoE) gene, a risk factor for Alzheimer's disease, also have been reported to be associated with cancer-related cognitive decline.…”

Section: Resultsmentioning

confidence: 99%

“…Neuroimaging studies of younger survivors have shown postchemotherapy decreases in frontal gray matter volume, abnormalities in brain network structure, and lower hippocampal volume consistent with aging. [18][19][20][21] We suggest that future research on mechanistic pathways focus on areas of overlap among aging processes, Alzheimer's disease, and risks for cancer-related cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Mandelblatt

Small

Luta

et al. 2018

JCO

123

194

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Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores ( P = .05) and those initiating hormonal therapy having lower LM scores at 12 months ( P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant ( P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures ( P < .001); frailty was associated with baseline APE and self-reported decline ( P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Mandelblatt

Small

Luta

et al. 2018

JCO

123

194

View full text Add to dashboard Cite

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“…It has been suggested that chemotherapy accelerates the aging process in the brain 50 – 52 . Synaptophysin expression decreases during aging, and although the postsynaptic protein PSD95 also is reduced during aging, it is retained longer at the synapse when age increases 53 – 55 .…”

Section: Discussionmentioning

confidence: 99%

Cisplatin treatment induces attention deficits and impairs synaptic integrity in the prefrontal cortex in mice

Huo

Reyes

Heijnen

et al. 2018

Sci Rep

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Patients treated for cancer frequently experience chemobrain, characterized by impaired memory and reduced attention. These deficits often persist after treatment, and no preventive or curative interventions exist. In mice, we assessed the effect of cisplatin chemotherapy on attention using the 5-choice serial reaction time task and on synaptic integrity. We also assessed the capacity of mesenchymal stem cells to normalize the characteristics of chemobrain. Mice were trained in the 5-choice serial reaction time task. After reaching advancement criteria at a 4-second stimulus time, they were treated with cisplatin followed by nasal administration of mesenchymal stem cells. Cisplatin reduced the percentage of correct responses due to an increase in omissions, indicating attention deficits. Mesenchymal stem cell treatment reversed these cisplatin-induced deficits in attention. Cisplatin also induced abnormalities in markers of synaptic integrity in the prefrontal cortex. Specifically, cisplatin decreased expression of the global presynaptic marker synaptophysin and the glutamatergic presynaptic marker vGlut2. Expression of the presynaptic GABAergic marker vGAT increased. Nasal mesenchymal stem cell administration normalized these markers of synaptic integrity. In conclusion, cisplatin induces long-lasting attention deficits that are associated with decreased synaptic integrity in the prefrontal cortex. Nasal administration of mesenchymal stem cells reversed these behavioural and structural deficits.

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“…Our study was conducted using a US-based population electronic medical record data set and a substantially larger number of women with breast cancer than previously reported. [14][15][16][17][18][19] Furthermore, we investigated the risk of developing multiple age-associated NDDs that occur sporadically within an aging population. We report the association of individual hormonal modulators and their drug families within the HMT category with the risk of development of age-associated NDDs.…”

Section: Introductionmentioning

confidence: 99%

Association Between Hormone-Modulating Breast Cancer Therapies and Incidence of Neurodegenerative Outcomes for Women With Breast Cancer

et al. 2020

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IMPORTANCE The association between exposure to hormone-modulating therapy (HMT) as breast cancer treatment and neurodegenerative disease (NDD) is unclear. OBJECTIVE To determine whether HMT exposure is associated with the risk of NDD in women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used the Humana claims data set from January 1, 2007, to March 31, 2017. The Humana data set contains claims from privatepayer and Medicare insurance data sets from across the United States with a population primarily residing in the Southeast. Patient claims records were surveyed for a diagnosis of NDD starting 1 year after breast cancer diagnosis for the duration of enrollment in the claims database. Participants were 57 843 women aged 45 years or older with a diagnosis of breast cancer. Patients were required to be actively enrolled in Humana claims records for 6 months prior to and at least 3 years after the diagnosis of breast cancer. The analyses were conducted between January 1 and 15, 2020. EXPOSURE Hormone-modulating therapy (selective estrogen receptor modulators, estrogen receptor antagonists, and aromatase inhibitors). MAIN OUTCOMES AND MEASURES Patients receiving HMT for breast cancer treatment were identified. Survival analysis was used to determine the association between HMT exposure and diagnosis of NDD. A propensity score approach was used to minimize measured and unmeasured selection bias.

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Probability of Alzheimer's disease in breast cancer survivors based on gray‐matter structural network efficiency

Cited by 32 publications

References 45 publications

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Cisplatin treatment induces attention deficits and impairs synaptic integrity in the prefrontal cortex in mice

Association Between Hormone-Modulating Breast Cancer Therapies and Incidence of Neurodegenerative Outcomes for Women With Breast Cancer

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