Optimizing Brain Health

May 29, 2015

Mijail Serruya, MD, PhD

Assistant ProfessorDepartment of Neurology

Thomas Jefferson University

COGNITIVE CHEER

Quis ego sum? Ego sum cerebrum!

Outline• The Pillars of Brain Health• Primary Care

– The Triad– Annual checks

• Sleep• Nutrition• Medication Side-Effects

– Chemo-brain?• Meditation, yoga, Qi-Gong, hypnosis• Nootropics• Pillars Recap and Summary

What Is Brain Health?• Cognition

– Memory– Attention– Executive function– Processing Speed– Language– Visuospatial

• Mood• Insight, self-awareness• Arousal, alertness• Independent function

– Managing finances, driving, self-care• Being true to oneself: self-compassion, integrity• Being true to loved ones: lovingkindness

Three Pillars of Brain Health• Regular, aerobic physical exercise• Daily cognitive engagement• Regular social engagement

Physical Exercise• Physical exercise is not a lifestyle choice it is a medicine• 3 x week• 30 min at a time• Till out of breath and sweating• If you encountered difficulties creating an aerobic exercise plan

(for example due to neuropathy), consider:– Reclined bicycle (cannot fall)– Supervised aquatherapy (weight supported)– Physical therapy / trainer

• If you found yourself not doing the exercise regularly despite wanting to, explicitly DELEGATE A PARTNER!

• Regular aerobic exercise is the ONLY treatment that can not only slow cognitive decline AND “turn back the clock” and restore healthy cognition!

Cognitive Engagement• Engage in some kind of cognitively engaging

activity daily• Minimize television or passive Internet browsing

to, on average, no more than 1 hour per day• Crossword puzzles, Sudoku, playing a musical

instrument, art work, attending lectures, taking a class, reading books

Cognitive Engagement• Computerized training (e.g., Lumosity)• For a minority of those playing these “brain

training” games, the benefits do generalize to improving memory and attention in daily life

• For the majority, you only get good at the game being practiced

• My advice: if you enjoy playing computerized games, go ahead, otherwise pursue an activity you enjoy

Social Engagement• Get out of the house more than once per week• Engage with other people beyond your immediate

family• Volunteer• Attend religious services• Take a class• Visit a petting zoo or have a support animal visit• Have a poker night, go bowling, play golf, play

tennis• Attend musical concerts• Visit museums and art galleries

Primary Care• Make sure you follow-up with your primary care

physician regularly!• Healthy blood pressure• Healthy blood sugar• Healthy blood cholesterol• Good management of these three aspects of

health has been shown to delay the onset and slow cognitive decline!

Primary Care• Annual check of vision and hearing• If you can’t hear or see well, there is no way your brain

can pay attention or encode new information properly• If you are prescribed glasses or hearing aids, wear

them• Every year, make sure your primary care checks:

– Thyroid function (TSH = thyroid stimulating hormone)– Vitamin B12 level– Vitamin D level– Iron levels– Disruptions in any of these can contribute to difficulties with

attention and memory, and they are all easy to address

Sleep• Regular sleep schedule• If having frequent insomnia or sleeping too much, or simply

waking up not feeling rested most days, let your doctor know• For insomnia, consider:

– A night-time ritual, warm bath with lavender salts– Chamomile tea or beverage with lemon balm, passionflower, valerian– Low-dose melatonin (0.25 to 0.5 mg, and can gradually increase to

higher doses) taken 14 hours after you wake up• If you snore often, you may need a sleep study! You must

inform your physician– Untreated frequent snoring can lead to heart failure, cognitive

decline and depression• If you have restless legs, your iron may be low: tell your doctor

Nutrition• Mediterranean diet

– Avoid carbs like the plague• If the food is colored white, take flight

– Fish– Enormous amounts of vegetables and fruit

• In general, is better to get your vitamins and minerals from fruits and vegetables than taking them in pills

• Slow-squeezed veg/fruit juices• Alcohol?

– Moderate amount / social drinking may be protective– High amount bad news

Medication Side Effects• Polypharmacy: primum non nocere

– Continually review every single medication you take and make sure with your doctors why you are taking it and if it can be discontinued

– There are many medications that can impair memory, attention and mood

– Likewise, over time, you may no longer be able to tolerate a medication that you had tolerated for many years

– Whenever possible simplify• Common offenders

– Anti-cholinergics: oxybutynin or tolterodine for bladder incontinence– Tricylic anti-depressants– Certain anti-histamines– Even nasal steroids can alter cognition in some people!– Reflux medications, even proton-pump inhibitors (PPIs) that alter

stomach absorption of iron and that in turn can alter cognition

Chemotherapy• First let us distinguish between when you actually are taking

chemotherapy versus effects years after having taken it• Most studies show that the primary effect of chemotherapy on

cognition is when you are actually actively taking the chemo– People may experience cognitive clouding, fatigue, mood changes on

the day of or days following chemotherapy: these symptoms usually resolve

– If you experience frequent or prolonged cognitive changes while actively on chemo, let your doctor know

• Sometimes the agent can be changed such that the therapeutic benefit is maintained without the side effect

• Example: my patient on chronic chemo for a kidney transplant had impaired attention while on tacrolimus that improved when she was switched to cyclosporine, the effect was more than having had taken a stimulant

• This medication-specific effect on cognition can be measured (Rollin-Sillaire et al., 2013)

Chemo-Brain• Of the 9.6 million cancer survivors in the US who have

completed active treatment, many report cognitive difficulties, with labels such as "chemo brain," "not as sharp," "woolly-headedness," or the "mind does not work as quickly".

• Older cancer survivors experience a double jeopardy since they are at risk for memory impairments and mild cognitive impairment and because they are greater than 55 years of age.

• To date, most of our knowledge of cognitive impairment in cancer survivors comes from female breast cancer survivors.

• Cancer survivors want to live independently in the community for as long as possible however, these cognitive deficits may prevent this desired lifestyle.

(McDougall et al., 2014)

Chemo-Brain is Real• Adjuvant chemo is associated with cognitive

impairment in many studies– However some suggest this impairment may be

present in cancer survivors even without chemo (Ono et al., 2015)

• While most experience a significant rebound in cognitive function one year after ending chemo, cognitive decline tends to persist, even decades later (Koppelmans et al., 2012; Collins et al. 2014)

Chemo-Brain is Real• Chemotherapy-associated cognitive impairment can be measured

quantitatively and compared with those who have not had chemo:– Brain electrical activity is altered in those with attentional difficulties or fatigue

following chemo (Kam et al., 2015; Moore et al., 2014)– The thickness of brain gray matter is reduced in those with chemo who reported

cognitive impairment and not in those who had chemo and were cognitively fine (Lepage et al., 2014)

– Brain white matter (“connecting cables”) diminished over time (Deprez et al., 2012)– Brain metabolism, patterns of brain connectivity, and task activation may be altered

(de Ruiter et al., 2011; Sorokin et al., 2014; Piccirillo et al., 2015)– Blood levels of proteins related to inflammation (cytokines) correspond to cognitive

difficulties (Cheung et al., 2015)• Elevated interleukin-1-beta corresponded with lowered response speed• Interestingly, in those who had elevated interleukin-4 cognition was better, so the body may

have neuroprotective proteins also

– The development of cognitive difficulties may depend on individual pre-chemo risk factors

• Pre-chemo metabolism in brain areas related to executive function predicted subsequent fatigue and cognitive difficulties (Askren et al., 2014)

• Over-activation of frontal lobe areas is linked to working memory difficulties before ever getting chemo (Scherling et al., 2011)

Chemo-Brain is Not What You Think• A large review of the on literature on cognitive impairment

and memory deficits experienced by cancer survivors found that:– even though mental health declined after a cancer diagnosis, the

long-term outcomes of cancer survivors DID NOT DIFFER from persons without cancer in depression or cognitive function (McDougall et al., 2014)

• Another large analysis found that cognition was not associated with cancer survivorship and supports other research suggesting that chemo brain may be BIASED BY EXPECTATION and using self-report rather than objective cognitive measures (Porter, 2013)

• It was found that the amount of worry a patient reports before undergoing chemo or radiation, significantly correlated with working memory (Berman et al., 2014)

Chemo-Brain is Not What You Think• Research on neuropsychological difficulties among cancer patients has

focused on chemotherapy as a primary cause, yet several studies have now shown that some patients evidence cognitive weaknesses prior to chemotherapy.

• As an alternative to the 'chemo-brain' theory, this study examined the hypothesis that stress and coping style may be associated with observed neuropsychological difficulties among female cancer patients.– Reid-Arndt and Cox (2012) studied 36 women following surgery for breast cancer

and BEFORE any subsequent treatments– 27% exhibited deficits in verbal fluency, 14% exhibited deficits in at least one

measure of memory– Self-reported stress was correlated with deficits in memory, verbal fluency, and

attention– The use of passive coping styles appeared to underlie the relationship between stress

and neuropsychological deficits• Stereotype threat: in a study of patients all getting chemo, those randomized

to receive information about “chemo-brain” ended up reporting much higher level of cognitive complains and indeed did significantly worse on a word-learning task, than the other chemo patients who were not educated about “chemo-brain”

Chemo-Brain is Not What You Think• Psychological interventions aimed at mitigating worry may

help to alleviate cognitive dysfunction associated with life-threatening illness such as cancer

• Psychological mechanisms, such as coping style, affect cancer patients' experience of neuropsychological deficits

• Patient information may induce a stereotype threat, which affects self-reported cognitive function AND neuropsychological TEST PERFORMANCE in cancer patients for whom this information is relevant!

• So if I simply conclude saying: chemo-brain is real and inevitable, then simply from having heard that you will end up having more memory and attention problems than if I say, chemo-brain is controversial and people generally are not good at all at rating their own true cognitive abilities

Cognitive Concerns?• So what if I do have concerns about my memory,

attention, language, etc, either while receiving treatment (surgery, chemo, radiation or any combination of those) or having survived cancer?

• First: have insight that your expectations are incredibly powerful

• Second: consider your coping style and if there were any degree of depression, worry, anxiety, despair, obsessiveness, apathy, etc., seek counseling (psychiatrist, psychologist, social worker, pastor)

• Third: if you really feel there were cognitive issues that persistently interfered with daily life, then seek a formal evaluation with a cognitive neurologist / neuropsychologist

Enhancing Cognition• Following the Pillars of Brain Health (exercise,

cognitive activities, social engagement; healthy sleep; healthy diet) there are additional techniques to further enhance cognition

• Mindfulness-based meditation– Mindfulnessandmore.com/meditations– Try five to ten minutes once daily every single day for

at least one week and if helpful, continue• Yoga• Tai-Chi• Self-hypnosis• Qi-Gong

Cognitive Training Therapy• Your doctor can write an order for “occupational therapy” or

“speech therapy” and in the comments of the order write “cognitive rehabilitation” and then you can work with an occupational therapist or speech therapist on particular attention, memory, or language issues that are affecting your day-to-day life (like Adeline “Addy” Schultz here at Jefferson)– https://rhonapaul-cohen.com/

• Some groups offer home-based occupational therapy, you can ask about the “Skills2Care” program– Evidence-based workbook-guided strategies to enhance home

independence• Home safety• Finances• Memory cues, attention

Kitchen Timer• Write list of tasks on piece of paper• Turn actual physical kitchen timer, put time for

each task– When timer goes off must finish task– Go to next task– Unfinished task defer or reschedule– Make the timer/paper pad or smartphone take over

function of dysfunctional frontal lobe / basal ganglia / cerebellum

Turn Off Auto-Pilot!• Concrete attention/memory strategies to teach patients, from

Rhona Paul-Cohen, Speech Therapist:– Lose your iPhone? Keys? Important letter?

• Get a super-ugly placemat and a TRANSPARENT bin from dollar-store• Train yourself to ALWAYS put your things in that bin• Why ugly? Attract your attention• Why transparent? So you can see what’s in there!• So even if not remember how the keys got in there, will always know where to

look for them

– Wandering in and out of rooms, what was I doing? Running on empty?• If go into kitchen to empty dishwasher block your own exit with a chair, when you

crash into it you will laugh and remember what you came to do• Get a bright sticker, whatever most catches your eye, with word ‘gas’ on it and

put on side of rear-view mirror: can’t miss it• Put two rubber-bands in an ‘X’ on your credit card: every time you take it out and

put it away you will physically have to remove or replace them, this catches your attention and makes you aware of what you are doing

– Use Routines– Sequentialize tasks

Psychotherapy• Mental health• Psychiatry• Psychology• Social work, psychiatric nurse, pastoral care• Cognitive-behavioral therapy• Psychodynamic therapy• Insight-guided therapy• Mindfulness therapy• Art, music, other types of creative exchange and

training

Enhancing Cognition: Nootropics• Nootropics are medications, whether prescription or

over-the-counter, that have been shown to improve some aspect of cognition

• Typically, psychiatrists and neurologist prescribe nootropics, in some cases primary care providers or oncologists will

• There are no prescription medications specifically approved for cancer-related cognitive or mood impairments, hence either you must have a diagnosis of something else (e.g., depression, adjustment disorder, attention-deficit disorder, mild cognitive impairment) or your prescriber and you agree to try something off-label

Prescription Nootropics• Acetylcholinesterase inhibitors

– Improve basal forebrain cholinergic tone– Approved for Alzheimer’s disease– Have been used off-label for attention-deficit, stroke, brain injury– Donepezil (Aricept) tablet– Galantamine (Razadyne) tablet– Rivastigmine (Exelon) tablet or skin patch

• Excitoprotectants / NMDA-antagnosists– Appear to boost catecholamine transmission– Amantadine (approved for Influenza A and Parkinson’s)– Memantine (Namenda; approved for moderate to severe Alzheimer’s)– Dextromethorphan (with quinidine; approved for psuedobulbar affect)– Has been used off-label for attention-deficit, headache

• Stimulants– Approved for attention-deficit disorder: dextroamphetamine (Adderall), methylphenidate (Ritalin, Concerta),

lisdexamfetamine (Vyvanse), dexmethylphenidate (Focalin)– Approved for sleep disorders: modafinil (Provigil), armodafinil (Nuvigil)

• Pro-catecholaminergic anti-depressant/anxiolytics (SNRIs)– Buproprion (Wellbutrin), venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta)

• Pure SNRI for ADD:– Approved for attention-deficit disorder: atomoxetine (Strattera);

• Blood pressure medications that enhance attention– Approved for attention-deficit disorder: clonidine (Catapres), guanfacine (Intuniv)

• Medium chain triglycerides (similar to what is in coconut oil)– Approved for Alzheimer’s disease: Axona food supplement

Over-the-Counter Nootropics• Always inform your doctor if you choose to take a supplement: they can have side

effects and interact with prescription medications• Each of the following has been shown to benefit memory or attention in double-blind

placebo-controlled trials, usually for people with attention-deficit, Alzheimer’s disease, stroke or brain injury:

• Bacopa monnieri, water hyssop– 225 to 300 mg once daily

• Huperzia serrata, club moss• Punica granatum, pomegranate

– 2 grams (POMx) once daily• Rhodiola rosea, golden root• Pinus pinaster, maritime pine• Pinus radiata, Monterey pine• Souvenaid • N-acetyl-cysteine

– 1.5 grams twice daily• Phosphatidylserine

– 200 to 300 mg once daily• L-acetylcarnitine• Certain types of coconut oil, krill oil

Experimental• You can always check clinicaltrials.gov to look for

trials throughout Philadelphia and the world that explore ways to enhance mood, memory, attention and wellbeing

• Some ongoing include:– Transcranial direct current stimulation– Guided psilocybin (hallucinogen) use

Summary• Pillars of Brain Health

– Big 3: Physical exercise, cognitive activities, social engagement– Supportive 2: Healthy sleep habits, healthy nutrition

• Primary care: regular follow-up– Blood pressure, blood sugar, cholesterol– Vision and hearing care– Simplify medications

• Meditation, yoga, tai-chi, qi-gong• Occupational/speech therapy• Mental health/psychotherapy• Regular, aerobic exercise• Daily cognitive activities• Regular, social engagement

If time:Qi-Gong Practice

Self-Hypnosis Practice

Qi-Gong• Swing arms at side• Ball in the air above head• Figure 8 on its side• Shout it out toss, inhale gather touch chest, shout

out fling out arms• Rev up shoulder blades inhale-slap thighs exhale• Swing arms at side

Pace-and-Lead Induction• Three things that are true• Reasonable Suggestion• Repeat• Only a few minutes

FIN

References for Supplements• Bacopa monnieri, water hyssop• 225 to 300 mg once daily• BacoMind (TM) (Natural Remedies, Pvt., Ltd., Bangalore, India).• Dave, et al. An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-

deficit hyperactivity disorder in children. Adv Mind Body Med. 2014.• Katz, et al. A compound herbal preparation in the treatment of children with ADHD: a randomized controlled trial. J Atten Disord. 2010.• Morgan and Stevens. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled,

double-blind trial. J Altern Complement Med. 2010.

• N-acetyl-cysteine• 50 mg/kg/day• Take 2 grams (2000 mg) twice daily (4 grams total in 24 hours) for one week THEN take 1.5 grams twice daily (3 grams total in 24 hours)• Benefit usually seen after 3 months• Hoffer, et al. Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo controlled

study. PLoS One. 2013.• Adair, et al. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology. 2001.

• Punica granatum, pomegranate• 2 g of pomegranate extract (in 2 POMx pills) once daily for six weeks• Ropacki, et al. Pomegranate Supplementation Protects against Memory Dysfunction after Heart Surgery: A Pilot Study. Evid Based Complement

Alternat Med. 2013.• Bookheimer, et al. Pomegranate juice augments memory and FMRI activity in middle-aged and older adults with mild memory complaints. Evid

Based Complement Alternat Med. 2013.

• Phosphatidylserine• 200 mg once daily for ADHD; 300 mg once daily for Alzheimer's disease• Hirayama, et al. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a

randomised, double-blind, placebo-controlled clinical trial. J Hum Nutr Diet. 2014 Apr;27 Suppl 2:284-91.• Manor et al. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a

double-blind placebo controlled trial, followed by an open-label extension. Eur Psychiatry. 2012 Jul;27(5):335-42. (the formulation in this study commercialized as Vayarin® that includes 75 mg phosphotidylserine, EPA, DHA.)

• Moré et al. Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer's disease and dementia. Adv Ther. 2014 Dec;31(12):1247-62.

References for Supplements• Huperzia serrata, Chinese club moss• Huperzine A• 0.1 to 0.2 mg twice daily• Xu, et al. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys. 2012. This study supported the use of

Huperzine A in patients with vascular dementia.• Rafii, et al. Alzheimer's Disease Cooperative Study. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology. 2011. This study

found that Huperzine A had no benefit for patients with Alzheimer's disease.

• Zinc sulfate• 150 mg once daily• Bilici, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol

Biol Psychiatry. 2004.

• Rhodiola rosea, golden root• 270 mg (ADAPT-232 containing Rhodiola rosea, Schisandra chinensis , Eleutherococcus senticosus)• Darbinyan, et al. Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose

regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000.• Aslanyan, et al. Double-blind, placebo-controlled, randomised study of single dose effects of ADAPT-232 on cognitive functions. Phytomedicine. 2010.

• Pinus pinaster, maritime pine• patented formula Pycnogenol tested in trials• 1 mg/kg/day• Trebatická, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry. 2006.

• Pinus radiata, Monterey pine• Enzogenol• 1000 mg once daily• Usually takes 6 weeks for effect• Theadom, et al. Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol. 2013

• L-acetylcarnitine• Jiang, et al. Oral acetyl-L-carnitine treatment in hepatic encephalopathy: view of evidence-based medicine. Ann Hepatol. 2013. 24018499.• Abbasi, et al. Acetyl-L-carnitine as an adjunctive therapy in the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a

placebo-controlled trial. Child Psychiatry Hum Dev. 2011. 21336630.

References for Supplements• Souvenaid (commercialized by Nutricia)• This nutritional supplement contains:

– Eicospentaenoic acid, 300 mg– Docosahexaenoic acid, 1200 mg– Phospholipids 106 mg– Choline, 400 mg– Uridine monophosphate, 625 mg– Vitamin E (alpha-tocopherol equivalents), 40 mg– Selenium, 60 µg– Vitamin B12, 3 µg– Vitamin B6, 1 mg– Folic acid, 400 µg– Vitamin C, 80mg

• Pardini et al. Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study. Neurodegener Dis. 2015;15(1):58-62.

• de Waal et al. The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study. PLoS One. 2014 Jan 27;9(1):e86558.

• Shah et al. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2013 Nov 26;5(6):59.

References for Studies• Askren MK, Jung M, Berman MG, Zhang M, Therrien B, Peltier S, Ossher

L, Hayes DF, Reuter-Lorenz PA, Cimprich B. Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation. Breast Cancer Res Treat. 2014 Sep;147(2):445-55.

• Berman MG, Askren MK, Jung M, Therrien B, Peltier S, Noll DC, Zhang M, Ossher L, Hayes DF, Reuter-Lorenz PA, Cimprich B. Pretreatment worry and neurocognitive responses in women with breast cancer. Health Psychol. 2014 Mar;33(3):222-31.

• Chan RJ, McCarthy AL, Devenish J, Sullivan KA, Chan A. Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer. Eur J Cancer. 2015 Mar;51(4):437-50.

• Cheung YT, Ng T, Shwe M, Ho HK, Foo KM, Cham MT, Lee JA, Fan G, Tan YP, YongWS, Madhukumar P, Loo SK, Ang SF, Wong M, Chay WY, Ooi WS, Dent RA, Yap YS, Ng R,Chan A. Association of pro-inflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: A multi-centered, prospective, cohort study. Ann Oncol. 2015 Apr 28.

• Deprez S, Amant F, Smeets A, Peeters R, Leemans A, Van Hecke W, Verhoeven JS, Christiaens MR, Vandenberghe J, Vandenbulcke M, Sunaert S. Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol. 2012 Jan20;30(3):274-81.

• de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, van Dam FS, Nederveen AJ,Boven E, Schagen SB. Cerebral hyporesponsiveness and cognitive impairment 10years after chemotherapy for breast cancer. Hum Brain Mapp. 2011Aug;32(8):1206-19.

• Kam JW, Brenner CA, Handy TC, Boyd LA, Liu-Ambrose T, Lim HJ, Hayden S,Campbell KL. Sustained attention abnormalities in breast cancer survivors with cognitive deficits post chemotherapy: An electrophysiological study. Clin Neurophysiol. 2015 Mar 21.

• Lepage C, Smith AM, Moreau J, Barlow-Krelina E, Wallis N, Collins B, MacKenzieJ, Scherling C. A prospective study of grey matter and cognitive function nalterations in chemotherapy-treated breast cancer patients. Springerplus. 2014Aug 19;3:444.

• Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol. 2012 Apr 1;30(10):1080-6.

• McDougall GJ Jr, Oliver JS, Scogin F. Memory and cancer: a review of the literature. Arch Psychiatr Nurs. 2014 Jun;28(3):180-6.Porter KE. "Chemo brain"--is cancer survivorship related to later-life cognition? Findings from the health and retirement study. J Aging Health. 2013 Sep;25(6):960-81.

• Moore HC, Parsons MW, Yue GH, Rybicki LA, Siemionow W. Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction. Support Care Cancer. 2014 Aug;22(8):2127-31.

• Moore HC. An overview of chemotherapy-related cognitive dysfunction, or'chemobrain'. Oncology (Williston Park). 2014 Sep;28(9):797-804.

• Ono M, Ogilvie JM, Wilson JS, Green HJ, Chambers SK, Ownsworth T, Shum DH. Ameta-analysis of cognitive impairment and decline associated with adjuvant chemotherapy in women with breast cancer. Front Oncol. 2015 Mar 10;5:59.

• Piccirillo JF, Hardin FM, Nicklaus J, Kallogjeri D, Wilson M, Ma CX, CoalsonRS, Shimony J, Schlaggar BL. Cognitive Impairment after Chemotherapy Related to Atypical Network Architecture for Executive Control. Oncology. 2015 Feb 7.

• Scherling C, Collins B, Mackenzie J, Bielajew C, Smith A. Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study. Front Hum Neurosci. 2011 Nov 1;5:122.

• Sorokin J, Saboury B, Ahn JA, Moghbel M, Basu S, Alavi A. Adverse functional effects of chemotherapy on whole-brain metabolism: a PET/CT quantitative analysis of FDG metabolic pattern of the "chemo-brain". Clin Nucl Med. 2014 Jan;39(1):e35-9.

• Reid-Arndt SA, Cox CR. Stress, coping and cognitive deficits in women after surgery for breast cancer. J Clin Psychol Med Settings. 2012 Jun;19(2):127-37.

• Rollin-Sillaire A, Delbeuck X, Pollet M, Mackowiak MA, Lenfant P, Noel MP, Facon T, Leleu X, Pasquier F, Le Rhun E. Memory loss during lenalidomide treatment: a report on two cases. BMC Pharmacol Toxicol. 2013 Aug 12;14:41.

Pillars of Cognitive Health

• Regular, aerobic exercise• Daily cognitive activities• Regular, social engagement