Skip to main content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Advisory Council October 2015 Meeting Presentation: ADRD

Monday, October 26, 2015

Overview of Alzheimer’s Disease and Related Dementias

Ronald C. Petersen, Ph.D., M.D.
Mayo Clinic College of Medicine
Rochester, MN


AD Related Dementias

  • Frontotemporal lobar degeneration
  • Dementia with Lewy bodies
  • Vascular cognitive impairment-dementia


  • Degenerative etiology
  • Gradual progression
  • Basic neurological exam normal early
  • Clinical-pathology correlation 80-90%

Criteria for AD

  • National Institute on AgingAlzheimer’s
  • Association
  • Alzheimers and Dementia, May, 2011

Introduction to the Recommendations from the National Institute onAging-Alzheimer’s Association Workgroups on Diagnostic Guidelinesfor Alzheimer’s Disease

Clifford R. Jack, Jr, Marilyn S. Albert, David S. Knopman,Guy M. McKhann, Reisa A. Sperling, Maria C. Carrillo,Bill Thies, Creighton H. Phelps

Hypothetical Model of Dynamic Biomarkers of the Alzheimer’s Pathological Cascade

Line chart.
Jack et al: Lancet Neurol 2010

Prevalence of PiB PET in Normals

Line chart.
Rowe et al: 2010

Biomarkers for AD

  • Early biomarkers
    • Amyloid deposition
      • PET imaging
      • CSF amyloid
  • Later biomarkers
    • Neurodegeneration
      • Structural MRI
      • FDG PET
      • Tau PET
      • CSF tau


Neuroimaging in AD

Neuroimaging in AD

  • Structural MRI
  • Functional imaging
    • FDG PET
  • Molecular imaging
    • Amyloid PET imaging


Structural Imaging in AD

Structural MRI: Atrophy and AD Stage

Control, 70, F MCI, 72, F AD, 74, F
Photo of brain MRI. Photo of brain MRI. Photo of brain MRI.


Functional Imaging in AD


Molecular Neuroimaging

PIB Idealized

  CN     aMCI     AD    
Brain images.

PIB Examples – Full Spectrum


Tau PET Imaging

Alzheimer’s Disease Spectrum

  • Preclinical AD
  • MCI Due to AD
  • Dementia Due to AD


Alzheimer’s Disease Treatments2015

Theoretical Drug Responses

Alzheimer’s Disease
Course, Prevention, Treatment Strategies

Intervention Primary prevention Secondary prevention Treatment
Clinical state Normal Pre-Clinical AD Mild cognitive impairment AD Dementia
Brain pathologic state
  • No disease
  • No symptoms
  • Early AD brain changes
  • No symptoms
  • AD brain changes
  • Mild symptoms
Mild, moderate or severe impairment
  • Identify at-risk
  • Prevent AD
Prevent or delay emergence of symptoms
  • Stimulate memory
  • Slow progression
  • Treat cognition
  • Treat behaviors
  • Slow progression
Disease progression






  • Passive immunization
    • Polyclonal antibodies
      • IVIG
    • Monoclonal antibodies
      • bapineuzumab
      • solanezumab
      • crenezumab
      • gantenerumab
      • aducanumab

Secretase Inhibition

  • Beta secretase inhibitors
    • Promising
  • Gamma secretase inhibitors
    • Challenges

Clinical Trials in the Era of Prevention

Autosomal Dominant 1% of AD E4/E4 asymptomatc 2% of population Amyloid Positive asymptom 30% of population aged 65+ Symptomatic MCI and Dementia 25% of population aged 65+


Lifestyle Modifications

Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer's Disease: A Randomized Trial

  • Nicola T. Lautenschlager; Kay L. Cox; Leon Flicker; et al.
  • JAMA. 2008;300(9):1027-1037 (doi:10.1001/jama.300.9.1027)


  • Moderate exercise (150 minutes/wk) resulted in improved cognitive function at 6 months
  • Some benefits maintained at 18 mos

So, where are we?



  • Clinical Spectrum -- CN - MCI - Dementia
    • TAU
    • Other
    • Vascular Disease
    • Alpha Synuclein
    • TDP-43

Clinical Pathology Biomarker Therapy

  • Clinical Spectrum -- CN - MCI - Dementia
      • PET/CSF
        • Rx?
    • TAU
      • PET/CSF
        • Rx?
    • Other
      • ?
        • Rx?
    • Vascular Disease
      • MRI
        • Rx?
    • Alpha Synuclein
      • ?CSF
        • Rx?
    • TDP-43
      • ?CSF
        • Rx?

Overall Conclusions

  • We can diagnose cognitive impairment fairly well
    • Clinical criteria
    • Biomarkers
  • Screening tools evolving
    • Useful in practice
  • Therapies being actively pursued

Thank You