Mild Cognitive Impairment

Dr M S KrishnanCampus For Ageing and Vitality

Learning Objectives

• Understand various definitions of MCI• Learn about clinical presentations• Consider various investigations• Learn About Predictors of MCI• Understand current treatment options• Discuss future of the concept of MCI

MCI

• It’s a clinically relevant concept• The concept is continuing to evolve • We can use some reliable criteria• The main focus is on prediction of outcome

and conversion• NOT NORMAL, NOT DEMENTED and• can we Treat????

History

• 1962 - benign senescent forgetfulness”• 1986 - age-associated memory impairment”

(AAMI)• age-associated cognitive decline by IAGP• Late 80s Reisberg et al Mild Cognitive

Impairment

It’s Cognitive continuum

Normal

Mid Cognitive Impairment

Dementia

CASE EXAMPLE

JOHN – 75 Retired Teacher• Forgetful• Gets frustrated when

dealing with various bills• Enjoys Bridge• Independent in all ADL skills• Wife does not see this as a

problem• John is worried if he is

developing AD

TOM – 78 Retired Bus Driver• Forgetful• Threads of conversation and

telephone messages• Looks after grand children

collects them from school• President of local club

organises events etc• Daughters are worried about

his memory he is not specifically concerned

Clinical Features

Concern regarding a change in cognition

• There should be evidence of concern about a change in cognition, in comparison with the person’s previous level.

• This concern can be obtained from the patient, from an informant who knows the patient well, or from a skilled clinician observing the patient.

Impairment in one or more cognitive domains

• There should be evidence of lower

performance in one or more cognitive domains that is greater than would be expected for the patient’s age and educational background.

Preservation of independence in functional abilities

• Persons with MCI commonly have mild problems performing complex functional tasks which they used to perform previously, such as paying bills, preparing a meal, or shopping

• They may take more time, be less efficient, and make more errors at performing such activities than in the past.

• Nevertheless, they generally maintain their independence of function in daily life, with minimal aids or assistance.

Not demented

• These cognitive changes should be sufficiently

mild that there is no evidence of a significant impairment in social or occupational functioning

Etiology

• There is heterogeneity in Presentation and possibility of multiple etiologies

• The predicted outcome of MCI can have a link to the etiology in a particular presentation

Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment

Journal of Internal MedicineVolume 256, Issue 3, pages 240-246, 20 AUG 2004 DOI: 10.1111/j.1365-2796.2004.01380.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2004.01380.x/full#f1

Pathophysiology

• In autopsy of MCI– Amnestic MCI – Similar changes like AD– Non Amnestic – CVD, FTD or no pathology

• Lab Studies– Biomarkers as Apolipoprotein E ????

• Neuroimaging– Hippocampal atrophy???– Hypoperfusion on functional imaging???

Baseline Tests

• Neuropsychological Assessment – Baseline– Below normal cut off (1,1.5,2 SD is debatable)

• Neuroimaging– No Specific Predictive Parameters– Some evidence that whole hippocampal volume

on MRI predicting progression of MCI to AD (Risacher et al)

– PET imaging + episodic memory impairment may predict conversion (Landau SM et al)

CASE EXAMPLE

JOHN – 75 Retired Teacher• Hypertensive on treatment

had MI 8 years ago• MMSE 27/30• CT Scan Normal• SPECT – Mild temporal

hypoperfusion on the left

TOM – 78 Retired Bus Driver• Not on any regular

medication apart from painkiller for arthritis as required

• MMSE 28/30• CT – Age related

involutional change• SPECT – Normal

Treatment

• Currently no established drug treatment available

• Trials have proven negative in use of Choline esterase inhibitors

• Diet: Vascular risk factors• Activity: Physical exercise and social

stimulation

No evidence for cognitive exercise puzzles etc

Treatment

Treatment

Prognosis

• Many patients with MCI eventually progress to AD

• Research quotes variable figures on rates of conversion ( average of 15% annually)

• Patients with MCI 7 times more likely to develop AD

• 80% of patients diagnosed with MCI are said to progress to AD by 6 years (Boyle et al)

Prognosis - Predictors

• Severity of Memory Impairment• Whole Brain and Hippocampal volume on MRI• ApoE Status (Not recommended for routine

clinical use)

CASE EXAMPLE after 18 months

JOHN – 75 Retired Teacher• More forgetful now unable

to do banking• Not able to go to unfamiliar

places• Difficulty in playing bridge• CT medial temporal atrophy

bilaterally • MMSE 23/30

TOM – 78 Retired Bus Driver• Remains forgetful• No major changes• Still drives no concerns• Had a DVLA assessment and

passed• MMSE 25/30• Daughter continues to

express concerns

Conclusion

• MCI is becoming an increasingly important clinical entity

• The focus remains on amnestic MCI which may be a prodrome/precursor of AD

• NOT NORMAL, NOT DEMENTED• Will Need Monitoring• No current evidence of specific treatment

References• Risacher SL, Saykin AJ, West JD, Shen L, Firpi HA, McDonald BC;

Alzheimer's Disease Neuroimaging Initiative (ADNI). Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort.Current Alzheimer Research. Aug 2009;6(4):347-61.

• Landau SM, Harvey D, Madison CM, Reiman EM, Foster NL, Aisen PS. Comparing predictors of conversion and decline in mild cognitive impairment. Neurology. Jul 20 2010;75(3):230-8.

• Boyle PA, Wilson RS, Aggarwal NT, et al. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology. Aug 8 2006;67(3):44