Collaboration. A Collaborative Approach to Addressing Sleep & Cognition 10/26/2017. Disclosures. Memory Clinic Team. Role of Neurologist

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1 A Collaborative Approach to Addressing Sleep & Cognition Disclosures Neither Drs. Ebert or Dexter have any relevant financial relationships with the manufacturer of any commercial product and/or provider of commercial services discussed in this CME activity. Amber Ebert, PsyD, LP Coram Consulting, LLC Donn Dexter, MD, FAAN Assistant Professor of Neurology, Mayo Clinic College of Medicine and Science 2017 Wisconsin Neurological Society Annual Conference Elkhart Lake, October 27-28, 2017 Memory Clinic Team Collaboration Neurologist Clinical Psychologist Social Worker Nurse Practitioner Role of Neurologist Leads the team Conducts complete neurologic assessment and examination Assembles and integrates information from all the team members in making a diagnosis and treatment plan Arranges long term follow up Role of Assessment Understand the nature of any brain injury or cognitive problem (e.g. memory, thinking, attention) and its impact on the individual Assists in differential diagnosing Assists neurologist in medication choices and determining effectiveness Identifies important safety factors for the individual and their caregivers 1

2 Role of Assessment (con t) Brief Neuropsychological Battery Clearly identifies which parts of the brain are working well and the individual s relative areas of weakness; can lead to further assessment Accurate diagnosis leads to more effective treatment plans Measure change in functioning over time Initial testing compared to same-age peers Once baseline is established, can re-test in the future and compare to peers and to previous individual results to track changes Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Recent memory and learning Language assessment Visuospatial processing Attention Mini-Mental State Examination (MMSE) Orientation/Memory Animal Fluency Language Brief Neuropsychological Battery (con t) Trails A Attention Trails B Executive function Clock Drawing Executive function Wide Range Achievement Test (WRAT-4), Word Reading Pre-morbid functioning Pilot Study A Pilot Study Identifying a Unique Pattern on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) that Predicts Obstructive Sleep Apnea (OSA) in a Dementia Screening Setting Case Report Patient ID: 62 year old, right-handed, DWM, veterinarian. Chief complaint: There is an obelisk in the way of my thinking. HPI: 18 month history of worsening short term memory, also noted by others; affected work; ADLs and personality unchanged (Lawton 8/8) Social history: divorced, three grown children, lives alone, no tobacco use, rare alcohol Family history: positive for Alzheimer's Disease in mother Case Report History (con t) Past medical/surgical illnesses: CAD, HTN, colon cancer, CABG, ascending aortic aneurism repair ROS: denies headache, snoring, or sleepiness Exam: - height: 1cm, weight: 111kg; BMI: BP: 124/68; neck circumference: 44cm General and Neurological exam: normal Mini Mental Status Exam: 30/30 2

3 Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Graph presented to Neurologist Jan 2013 IM: (25%) V/C:131 (98%) Lang:105 (63%) Attn:97 (42%) DM:98 (45%) Total:105 (63%) Impact on Treatment Approach Diagnosis, Treatment & Follow-Up Despite the patient's negative history and benign exam, a sleep study was ordered based on the RBANS IM<DM pattern shown on testing Prior to identification of this pattern Considered these results essentially normal Followed with repeat testing in 6 to 12 months Diagnosis: OSA, moderately severe on basis of elevated AHI of 17 and desaturations to 83% Treatment: CPAP, auto-titration Follow-up: CPAP compliance excellent, reported feeling better, memory clearer Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Re-test Graph presented to Neurologist Jan 2013 Aug 2013 IM: (25%) IM:117 (87%) V/C:131 (98%) V/C:126 (96%) Lang:105 (63%) Lang:116 (86%) Attn:97 (42%) Attn:118 (88%) DM:98 (45%) DM:112 (79%) Total:105 (63%) Total:127 (96%) 3

4 Memory Loss and Obstructive Sleep Apnea A cognitive pattern was noted in patients previously diagnosed or suspected to have Obstructive Sleep Apnea (OSA). The Immediate Memory was less than Delayed Memory (IM<DM). This is the opposite of a typical Alzheimer's pattern and different than a vascular dementia pattern. Based on this observation, we conducted a retrospective review of MCC patients from December December Is this a unique pattern (IM < DM) that predicts OSA? There is very limited research looking at RBANS/OSA relationship. Cautions: - Small sample size (N=10) - 60% of sample not tested for OSA - Observational study only Retrospective review data 72 patients seen in MCC in study period 29 had IM < DM pattern (40%) 13 tested for OSA (18%) Of tested, 10 OSA + (77%) N=72 N=29 % of total (N=72) % of pattern (N=29) % of tested (N=13) No pattern Pattern Untested OSA OSA Discussion Based on a small observational study, a unique pattern on the RBANS seemed to predict OSA. Not previously noted or reported. Etiology is unclear but hypoxemia directly affecting hippocampal function, disrupted sleep (with decreased amyloid clearance or other cause) or some other explanation may be possible. Treatment of OSA may improve memory and other cognitive functions. Case Report 3 Year Study A Unique Pattern on Memory Testing in Dementia Screening Predicts Obstructive Sleep Apnea Patient ID: 78-year-old, right-handed, Married White Female HPI: 12 month history of worsening memory, also noted by husband; ADLs and personality unchanged (Lawton 8/8) Family hx of memory changes Social hx: retired postmaster, never smoked, rare ETOH 4

5 Case Report History (con t) Past medical/surgical illnesses: HTN, hypothyroidism, pacemaker, dyslipidemia, depression, diabetes. Hx lung cancer tx w/ chemotherapy ROS: headache (more frequent in a.m.), no snoring, some daytime sleepiness Exam: height: 166cm, weight: 66kg; BMI: 23.7 BP: 152/78 General and Neurological exam: normal Mini Mental Status Exam: 30/30 Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Sept IM:76 (5%) V/C:89 (23%) Lang:108 (70%) Attn: (16%) DM: (25%) Total: (16%) Graph presented to Neurologist RBANS Retest After Treatment of OSA RBANS RBANS Sept March 2015 IM:76 (5%) IM: (25%) V/C:89 (23%) V/C:92 (30%) Lang:108 (70%) Lang:99 (47%) Attn: (16%) Attn:103 (58%) DM: (25%) DM:101 (53%) Total: (16%) Total:95 (37%) RBANS Retest After OSA Treatment RBANS RBANS repeat Retrospective Review of Data 191 patients seen in MCC in study period ( ) 81 had IM < DM pattern (42%) 54 were tested for OSA (67%) Of patients tested, 35 OSA + (65%) 27 patients with the pattern (33%) declined OSA testing Total N=191 Pattern N=81 % of total (N=191) % of pattern (N=81) % of tested (N=54) No pattern Pattern Untested OSA OSA

6 OSA Compared to Other RBANS Patterns OSA Compared to Other RBANS Patterns Other diagnoses: IM > DM OSA: IM < DM o Patients with OSA were the only group to score lower on immediate memory than delayed memory o The OSA memory pattern is demonstrated the largest spread between scores Alzheimer s Disease Vascular Dementia Mixed Alzheimer s/ Vascular Dementia Parkinson s Disease Depression HIV Dementia Huntington s Disease OSA Immediate Memory Delayed Memory (Spread) N *Taken from RBANS Manual (Randolph, 1998) Review of the Literature Discussion We found no articles or references to RBANS related to OSA. A number of articles describe Cognitive Impairments in patients with OSA We found no articles that described patients with Cognitive Impairments that would predict OSA This study confirms findings of our previous study. Multi-site Wisconsin Alzheimer s Institute study in planning stages. may be the primary etiology of this memory loss pattern. Discussion We have several patients with memory loss in the pattern described in our reports that showed significant improvement with treatment with Continuous Positive Airway Pressure (CPAP). The presence of sleep disordered breathing has been reported to cause cognitive decline in the elderly and treatment of this with CPAP has been shown to delay progression of cognitive decline (7). Our findings appear to be more robust and this may be due to the unique pattern we describe and the fact that the reversal of the immediate/delayed memory decline is an earlier or more specific finding. Given the clear confirmation of the immediate < delayed memory pattern predicting OSA and the strong positive effect seen with treatment of OSA in our patients, we strongly suggest routine screening in all patients with this pattern and aggressive treatment when OSA is discovered to reverse and perhaps prevent cognitive decline. Treatment 6

7 Overnight Pulse Ox We now routinely screen our patients with overnight pulse oximetry. This test is done at home, is non-invasive and inexpensive. Formal Polysomnography required for diagnosis and treatment approvals for OSA. Key Takeaways Key Takeaways 65% of patients with the IM<DM pattern (Immediate Memory lower than Delayed memory) had OSA Most patients showed significant cognitive improvement with treatment Patients showed decline on repeat testing if OSA was not treated. Without OSA treatment, patient scores eventually declined to a typical dementia pattern of IM>DM Early OSA diagnosis and treatment is key to preserving cognitive abilities Key Takeaways 1 in 5 patients referred to our Memory Care Clinic have OSA This number is likely underestimated due to some patients declining evaluation for OSA Body Mass Index (BMI) showed no statistically significant correlation Some patients also have an underlying organic dementing disorder, but even in those cases, treating the undiagnosed OSA improves cognitive clarity If OSA is treated, it can help maintain independence and keep the patient home longer Benefits of collaboration Team approach allows the gathering of more information, often seen from a new viewpoint Helps to alleviate the stress of seeing patients with these difficult conditions Reduces burnout Offers opportunities for research 7

8 References 1) A Pilot Study Identifying a Unique Pattern on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) that Predicts Obstructive Sleep Apnea (OSA) in a Dementia Screening Setting. Gerber, A., Dexter, D. Neurology. April 8, 2014 vol. 82 no. 10 Supplement P ) Effects of hypoxia on the brain: Neuroimaging and neuropsychological findings following carbon monoxide poisoning and obstructive sleep apnea. Gale, S., Hopkins, R., et. al. Journal of the International Neuropsychological Society, Vol.10, ) Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer s disease. Roh JH, Jiang H, Finn MB, et al. The Journal of Experimental Medicine. 2015; 212(1):121. 4) Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus. Vecsey, C.G., Peixoto, L., choi, J.H., et. al.; Physiological Genomics. 2012; 44(20): ) Sleep drives metabolite clearance from the adult brain. Xie,L., Kang,H., et. al.; Science 2013; 342 6) Self-reported sleep and beta-amyloid deposition in community-dwelling older adults. Spira, AP., Gamaldo, AA., et. al., JAMA Neurol 2013; vol 70 7) Sleep-disordered breathing advances cognitive decline in the elderly. R.S. Osorio, T. Gumb, E., Pirraglia, et al. Neurology, 84 (19) (2015), pp Questions? Contact information aebert@coramconsulting.net dexter.donn@mayo.edu 8) Repeatable Battery for the Assessment of Neuropsychological Status. Randolph, C. The Psychological Corporation. San Antonio, TX