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Incidence and Rates of Progression of Amnestic
and Non-Amnestic MCI Syndromes
Katie Palmer Marie Curie Fellow - European
Union IRCCS, Foundazione Santa Lucia, Rome, Italy
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The role of population-based studies

• Large samples
• Long follow-up time
• Identify also cognitively impaired individuals
  who do not seek medical attention
• Provide a picture of the real-life situation
• Evaluations less thorough than clinical
  examinations
• Longer follow-up times
• High mortality rates in the elderly may affect
  longitudinal estimates
• Long-term studies initiated before MCI criteria
  were proposed

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The Kungsholmen Project, Stockholm, Sweden
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Nine year incidence of MCI and CIND
Caracciolo et al, Neurology 2008
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Incidence of amnestic MCIPopulation-based studies

• Leila 75 project, Germany
• 3 years (AACD and amnestic MCI)
• 8-77.0 per 1000 person-years
• Paquid Study, France
• 5 years
• 9.9 per 1000 person-years
• Caide, Kupio Study, Finland
• 3 years
• 25.9 per 1000 person-years
• Italian Longitudinal Study on Aging
• 3 years
• 21.5 per 1000 person-years

Busse et al, 2003
Larrieu et al, 2002
Tervo et al, 2004
Solfrizzi et al, 2004
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Nine year incidence of MCI the affect of
attrition
Caracciolo et al, Neurology 2008
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Risk factors for incident cognitive impairment

• Risk factors for cognitive Impairment, after
  adjustment for future AD development
• Hip fracture. Relative risk 2.9 (1.17.8)
• Polypharmacy 5 drugs. Relative risk 3.1
  (1.28.0)
• History of psychosis. Relative risk 5.0
  (1.123.6)
• Risk factors for cognitive impairment, that are
  related to AD
• Depressive symptoms. Relative risk 1.9
  (1.13.1)

Monastero et al, Am J Geri Psychiatr 2007
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Prevalence of MCI per 100 non-demented people in
the general population
Palmer et al, Am J Geri Psychiatr 2008
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Three year progression from MCI to ADModifed vs
standard criteria

• MCI-Amnestic
  MCI-Multidomains

Standard criteria
Modified criteria
Modified criteria

• Standard
• criteria

• Hazard Ratios for progression from MCI to AD,
  adjusted for age, sex, education

Palmer et al, Am J Geri Psychiatr 2008
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Three year progression from MCI to AD
Alzheimers at
3-years RR (95 CI) Normal
functioning on all tests 1.0   Amnestic
MCI 9.3 (2.4-34.7) Single non-memory
MCI 2.4 (0.5-11.3) MCI Multiple domains
impaired 21.9 (9.7-49.5)      

• Hazard Ratios for progression from MCI to AD,
  adjusted for age, sex, education

Palmer et al, Am J Geri Psychiatr 2008
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MCI modified criteria Increase prevalence
without diminishing predictivity of AD

• Canadian Study of Health and Ageing
• Instrumental ADL
• Subjective memory complaints
• Leila 75 project, Germany
• Subjective memory complaints
• MoVIES study, USA
• Subjective memory complaint
• Paquid Study, France
• Instrumental ADL

Fisk et al, 2003
Busse et al, 2003
Ganguli et al, 2004
Peres et al, 2006
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Pooled analysis of amnestic MCI
progressionTemporal trends

• 15 long-term studies on MCI population based
  clinical studies
• Cumulative conversion rate from MCI to AD 31.4
• Mean annual conversion rate 3.3 (95 CI
  3.0-3.6)
• -Population studies 2.6
• -Clinical studies 6.7
• Conversion rates from MCI to AD are not linear

Mitchell et al, JNNP 2008
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Factors affecting MCI progression
Palmer et al, Neurology 2007
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Factors affecting MCI progression
Neurodegenerative MCI
MCI patients who do not progress to AD
Depression
Depression
Palmer et al, Neurology 2007
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Possible etiologies of MCI subtypes
International working group on MCI Consensus
Conference Stockholm 2003
Winblad et al, J Internal Med 2003
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Somatic factors that affect cognition
Global cognition
Episodic memory
Verbal fluency
Other domains
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Somatic factors that affect cognition
Global cognition
Episodic memory
Verbal fluency
Other domains
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Risk factors / early markers of AD?
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ConclusionsMethodological considerations for the
future

• Generally, incidence rate estimates are similar
• - Case definitions / criteria affect incidence
  prevalence estimates
• - Difficult to estimate affect of mortality
• Single- non-memory deficit MCI common in
  population-studies
• - Do these patients seek less medical care in
  memory clinics?
• Amnestic and Multidomain MCI high rate of
  progression to dementia
• Annual conversion rates from MCI to AD are not
  linear
• Neuropsychiatric disorders are common in MCI, and
  some predict progression to AD
• -Differentiating MCIdepression vs Depression
  cognitive deficits

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• COLLABORATORS
• Massimo Musicco Gianfranco Spalletta
• Fulvia di Iulio Carlo Caltagirone
• Italian National Research Council (CNR)
  Foundazione Santa Lucia, Italy
• Laura Fratiglioni Lars Bäckman
• Bengt Winblad Barbara Caracciolo
• Anna Karin Berger Roberto Monastero Anna
  Rita Atti
• Aging Research Center, NVS, Karolinska
  Institutet, Sweden
• Funding acknowledgements
• Marie Curie Intra-European Individual Fellowship
  (EU)