What is normal aging? What is mild cognitive impairment (MCI)? How do I know if I have Alzheimer's disease? Preventing dementia.

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Mild Cognitive
Impairment Spectrum
Monica K. Crane, MD
Director of Clinical Research
Associate Director, Cole Neuroscience Center
Clinical Assistant Professor of Medicine
Dept. of Medicine

2. Disclosures
• Board member of Alzheimer’s Tennessee
• Founding member of the International Society
of Frontotemporal dementia
• Grant/Research support: Biogen, Eisai.
2

3. Cognitive Aging is not a
disease
www.iom.edu/cognitive aging 2015

4. Cognitive Aging
• Everyone is affected.
• Thinking can improve with aging.
• Intact adults can strengthen some
cognitive abilities.
www.iom.edu/cognitive aging 2015

5. German psychologist Hermann Ebbinghaus in 1885.

6. Age appropriate atrophy?
www.iom.edu/cognitive aging 2015: The

7. •Progress?
•Fear?
•Curable?
•Prevented?
CANCER vs. DEMENTIA
7

8. • Symptom not a
diagnosis
• 100+ types
• Never normal in
aging
Dementia
Umbrella term

9. Mild Cognitive Impairment
(MCI)
An acquired disturbance in
cognition without impairment
in daily functioning.

10. http://www.re-cognitionhealth.com/other-causes.php
MCI
Alzheimer’s
Disease (AD)
FTD -
tau
FTD
TDP-43
PD/ LBD/
α-
synuclein
OTHER
MIXED

11. Who has MCI?
Dickerson. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimer's Research & Therapy 2010; 2:21
Meyer et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol 2010;67:949-956.
10-20% of those aged 65+ older may
have MCI.

12. Am I on the TIMELINE?

13. • Clinically “normal” range but may
have patterns or positive biomarker
for AD.
• Treated as “worried well” depressed,
anxious, etc.
Dickerson. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimer's Research & Therapy 2010; 2:21
Meyer et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol 2010;67:949-956.
What is preclinical or pre-MCI?

14. Criteria for Probable MCI due to AD
• Meets criteria for MCI
–History and physical, labwork
–Cognitive screens
• Impaired for age and education
• Clinical Dementia Rating Score of 0.5
• Computer Self Test (CST) of 27 or less
• MOCA of 26 or less
• and an objective biomarker:
Dickerson. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimer's Research & Therapy 2010; 2:21
Meyer et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol 2010;67:949-956.

15. Dickerson. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimer's Research & Therapy 2010; 2:21
Meyer et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol 2010;67:949-956.

16. 16
Cognitive tests: CST
Cannon R, Dougherty J,
Crane M, Dougherty A
(2010). Alzheimer's &
dementia : J Alz
Associa 6, e50-e51
[Dougherty JH, Jr.,
Cannon RL, Nicholas
CR, Hall L, Hare F, Carr
E, Dougherty A,
Janowitz J,
Arunthamakun J. . J
Alzheimers Dis 20, 185-
195.
.

17. 17
• 9/5/2013
• 70 yo female
memory
concerns.
• Diagnosis: MCI
amnestic variant
• MOCA 24
• Able to work.

18. 18
7/11/2014
•Diagnosis: overt
early Alzheimer’s
disease.
•MOCA 17
•Less than a year later
unable to continue
her career.

19. 6/22/16
Less than 2 years later.
Diagnosis: moderate AD
MOCA: Unable to
complete.
Unable to recognize
family and friends.

20. Diagnosis of >90% clinical accuracy?
• Biomarker is objective measure used as
evidence of a biological or pathological
process
• We use biomarkers daily in practice
Dickerson. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimer's Research & Therapy 2010; 2:21
Meyer et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol 2010;67:949-956.

21. Biomarkers for MCI due to AD
• Anatomy
• Functional or
metabolic change
(downstream)
• Pathology
– CSF Aβ-42
– CSF tau / phospho-
tau
– PET amyloid imaging
– Tau imaging
Additional IMAGING American Academy of Neurology guidelines. Arora A, Bhagat N.
Insight into the Molecular Imaging of Alzheimer's Disease. Int J Biomed Imaging. 2016

22. Foster DJ, Wilson MA. Nature 2006;440:680-683.
Foster DJ, Knierim JJ. Curr Opinion Neurobiol 2012;22:294-300.
Biomarker: Hippocampus
• Working memory
• Planning and
imagination
• Must be intact to
imagine the
“what ifs”…

23. Biomarker: Hippocampal atrophy
Normal Alzheimer’s
T1 MRI coronal view

24. Glucose Metabolism Using 18F-FDG
positron emission tomography (PET)

25. Amyloid PET to show plaque
Acta Neuropathol Commun. 2014; 2: 46.
2014 Apr 22.

26. Primary and secondary
prevention

27. FIXED risk factors for MCI
due to AD
• Age
• Family history 1° relatives
• Genetics
• Subjective memory impairment

28. • Lack of exercise
• Midlife obesity
• Low education
• Smoking
• Hypertension
• Diabetes
• Depression
• Sleep Apnea
7 FIXABLE RISK FACTORS
1/3 of
current AD
cases are
from these
7 factors
PAR, population attributable risk. Courtesy of Lancet Neurol. 2011 Sep; 10(9): 819–828.

30. Exercise slows MCI due to AD
• Slows decline on testing
and on functional MRI.
• Slows conversion to AD
JC Smith et al. Semantic Memory Functional MRI and Cognitive
Function After Exercise Intervention in Mild Cognitive
Impairment. Journal of Alzheimer’s Disease, 2013

31. • Lack of exercise
• Midlife obesity
• Low education
• Smoking
• Hypertension
• Diabetes
• Depression
• New risk factors
7+ risk factors for Alzheimer’s
that you can modify
1/3 of
current AD
cases are
from these
7 factors
PAR, population attributable risk. Courtesy of Lancet Neurol. 2011 Sep; 10(9): 819–828.

32. Protective activities reduce MCI
(median age 87.3)
• Art and crafts
• Social groups (volunteer, church,
group educational activities)
• Second language
• Musical instrument/ choir
• Computer (ONLY for 80+)
Roberts RO et al. Neurology 2015 Apr 8. Galvin JE. Neurology 2014 Apr 8.

33. • Lack of exercise
• Midlife obesity
• Low education
• Smoking
• Hypertension
• Diabetes
• Depression
• New risk factors
7+ risk factors for Alzheimer’s
that you can modify
1/3 of
current AD
cases are
from these
7 factors
PAR, population attributable risk. Courtesy of Lancet Neurol. 2011 Sep; 10(9): 819–828.

34. What diet is good for the brain???

35. Mediterranean diet
• Nuts, complex grains, olive oil
• Fruits and vegetables
• Coffee and Tea
• Omega-3 fats.
– Salmon, tuna, trout, sardines, seafoods.
• Avoid refined sugars, red meat and processed
foods
– Sugary desserts, baked goods
– Red meat, fast food, “diet” food
www.rand.org Meta-analysis 1.5 million people, 35 studies: Mediterranean diet
decreased risk of dementia death by 13%

36. • Lack of exercise
• Midlife obesity
• Low education
• Smoking
• Hypertension
• Diabetes
• Depression
• New risk factors
7+ risk factors for Alzheimer’s
that you can modify
1/3 of
current AD
cases are
from these
7 factors
PAR, population attributable risk. Courtesy of Lancet Neurol. 2011 Sep; 10(9): 819–828.

37. Sleep Apnea and
Alzheimer’s
• Untreated sleep apnea affects
spatial navigational memory.
• Untreated sleep apnea worsens
cognitive impairment.
The Journal of Neuroscience, 29 October 2014, 34(44): 14571-14577; doi: 10.1523/JNEUROSCI.3220-14.2014

38. Benefit of MINIMAL alcohol...

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FINDING A CURE

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