When is Memory Loss Significant? David Williamson, PhD (ABPP-Cn), MBA

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1 When is Memory Loss Significant? David Williamson, PhD (ABPP-Cn), MBA Third Annual Neuroscience Symposium Orange Beach, AL April 2016

2 Disclosures Dr. Williamson is an employee of Janssen Scientific Affairs, LLC. No statements made during this presentation relate to Janssen products, and none should be interpreted to represent the views of Janssen Scientific Affairs, LLC. The content and opinions expressed in this presentation are solely those of the presenters and not necessarily those of Janssen Scientific Affairs, LLC.

3 First Case of the Morning Dr. Reese is a 61-year old cardiologist. His family is concerned about some recent forgetfulness, errors in judgment, and subtle changes in personality. Dr. Reese denies any problems or changes. His family doc finds no problems, and he scores normally on the MMSE. He knows that he is nearing retirement, his first grandchild has just been born, and the delivery was complicated...

4 First Case of the Morning His primary care doc feels that he s probably just under a lot of stress, if there s anything there at all. The family is not so sure, and they are concerned about both liability issues and what they ve heard about early intervention being important with many conditions causing mental status changes. The doc, a friend of yours, knows that you have an interest and some expertise in these issues, and refers to you for a second opinion. What can they do next?

5 Case #2 Ms. Smith is a 68-year old retired housekeeper with a 4 th -grade education whose family is concerned about her recent memory problems. She has a long history of periods of depression, only once needing to be hospitalized. She has been feeling more down in the dumps over the past couple of months. Labs come back essentially normal, MMSE = 23. How concerned should you be about the early stages of a dementing process?

6 Medical Workup: Useful References Feldman et al (2008) CMAJ, 178(7), Guidelines from the National Institute on Aging-Alzhiemer s Association workgroups on diagnostic guidelines for Alzheimer s disease and mild cognitive impairment due to Alzheimer s disease

7 Biomarkers in Alzheimer s Disease Jack et al (2013) Lancet Neurol, 12(2),

8 McKhann et al. (2011). Alzheimer s & Dementia 7 (2011) Albert et al. (2011). Alzheimer s & Dementia 7 (2011)

9 When is Memory Loss Significant? History and Behavior

10 Memory Loss What are they describing? (Nature of complaint) Memory Working memory / concentration Remote memory Recent memory Procedural memory and/or praxis (how to do things) Anomia / word-finding Memory vs. other types of problems (cognitive & mood) Time course of problems

11 Developing the Cognitive Profiles Impact of Patient Background Age Education Ethnicity Assessing a Range of Cognitive Abilities Memory (Immediate, Delayed) Executive function Attention / working memory Language Processing Speed Visuoperceptual/constructional skills Praxis Role of Psychopathology

12 Knowing the Base Rates Prevalence of late-onset (>65 years) dementias Prevalence of young-onset (<65 years) dementias Alzheimer's disease Vascular dementia Other Estimated prevalence of 11 25% of depression in adults >55 years old 2 Alzheimer's disease Vascular dementia Frontotemporal dementia ETOH-related dementia Dementia with Lewy bodies Huntington's disease Other Van der Flier WM & Scheltens P (2005). J Neurol Neurosurg Psychiatry, 76(Suppl V):v2 v7. 2 Vaughan L et al. (2015). Clin Interv Aging, 10,

13 When is Memory Loss Significant? History and Behavior

14 Significant For What? Diagnosis Prediction of Function or Competency Driving Ability to make decisions Assessing Change over Time How much of a change is meaningful? How long should I wait between retests?

15 Source of Information Who is reporting the problem(s)? Patient Family / informant Performance on objective testing

16 Source of Information Self-report <> objective test performance! Subjective memory complaints In general, only weakly related to objective performance Influenced by mood and potentially progression of MCI / dementia 1 However, in elderly, some predictive utility for conversion to dementia 2 Informant report Generally more strongly related to objective performance and conversion Most strongly predictive combination is patient + informant 3 1 Mitchell AJ et al (2014). Acta Psych Scand, 130, Jessen F. (2014). Eur Arch Psychiatry Clin Neurosci, 264 (Suppl 1), S3-S7. 3 Jessen F et al (2014). Alz & Dem, 10,

17 Diagnosis The Role of Testing despite an understandable drive toward ultra-brief tests which can be used in a typically time-constrained general practitioner consultation, an administration time of more than 10 minutes appears to be an unavoidable cost of achieving sufficiently robust statistical performance while covering key domains. (pp 59-60) Lin et al 2013, AHRQ, Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Task Force. Available at:

18 Diagnosis: Screening Mini Mental State Examination (MMSE) 1 Sensitivity and specificity best with at least mild dementia Significant effects of age and education 2 Montreal Cognitive Assessment (MoCA) 3 Free ( Steadily accumulating more reliability and validity data MCI, MS, brain CA, Parkinson s Category & Phonemic Fluency Clock Drawing Informant Measures AD8 4 ( Mayo Fluctuation Questions 5 1 Folstein et al. (1975). J Psychiatr Res, 12, Crum et al. (1993). JAMA, 269(18), Nasreddine et al. (2005). J Am Geriatr Soc, 53, Galvin et al. (2005). Neurology, 65: Ferman T et al. (2004). Neurology, 62,

19 MMSE norms by Age and Educational Level Educational level AGE 0-4y 5-8y 9-12y >12y Assume age- and education-effects unless proven otherwise! 1 Adapted from Crum et al. (1993). JAMA, 269(18),

20 Improved Sensitivity of MOCA Trzepacz et al. BMC Geriatrics (2015) 15:107.

21 Prediction Conversion from MCI to dementia Measures of delayed recall outperform biomarkers in predicting conversion from MCI to AD 1 1 Gomar JJ et al (2011). Arch Gen Psychiatry Sep;68(9):961-9.

22 Prediction Conversion from MCI to dementia Measures of delayed recall outperform biomarkers in predicting conversion from MCI to AD 1 Driving Measures of psychomotor speed help provide an objective basis to estimate driving risk 2 Elevated driving risk has been linked to MoCA scores below 19 in cognitively impaired groups 3 1 Gomar JJ et al (2011). Arch Gen Psychiatry Sep;68(9): Wood JM & Owlsley C (2014). Gerontology, 60(4), Holllis AM et a;. (2015). J Am Geriatr Soc May;63(5):

23 Prediction Conversion from MCI to dementia Measures of delayed recall outperform biomarkers in predicting conversion from MCI to AD 1 Driving Measures of psychomotor speed help provide an objective basis to estimate driving risk 2 Elevated driving risk has been linked to MoCA scores below 19 in cognitively impaired groups 3 Competency / capacity Performance on tests of cognition, including shortterm memory, has been linked various legal competencies 4,5 1 Gomar JJ et al (2011). Arch Gen Psychiatry Sep;68(9): Wood JM & Owlsley C (2014). Gerontology, 60(4), Holllis AM et a;. (2015). J Am Geriatr Soc May;63(5): Triebel et al. (2010). Alz Dis Assoc Disord, 24(4), Okonkwo et al. (2008). J Int Neuropsych Soc, 14(2),

24 Diagnosis: Assessment of Change Published data are available to guide interpretation of changes seen in serial testing with MoCA 1 Other scales (e.g., ADAS-Cog, MMSE) available for assessment of change, depending on needs 1 Costa AS et al. (2014). Dement Geriatr Cogn Disord, 37(1-2),

25 When to Refer for Neuropsych +/- results in a bright patient, particularly in the presence of patient or family complaint Legal capacities are at issue but deficits are not yet striking Most capacities impaired at MMSE < 20 But potential educational confound Mild problems in someone with low education or language limitations

26 Back to the Clinic Dr. Reese. Mrs. Smith.

27 Questions?

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