Kaplan + Sadock's Synopsis of Psychiatry, 11e

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Chapter 21: Neurocognitive Disorders

progressive loss of function. However, several studies have indi- cated that the diagnosis is not stable in both directions; patients can either convert to Alzheimer’s disease or revert back to nor- mal. This variability in course is related to the heterogeneous source of the subjects (clinical vs. community) as well as to the heterogeneous definition criteria used by different studies. Amnestic MCI has been associated with increased morbidity compared with reference subjects. Treatment There are no FDA-approved treatments for MCI at this time. MCI treatment involves adequate screening and diagnosis. Ide- ally, MCI treatment would also include improvement of mem- ory loss together with prevention of further cognitive decline to dementia. Cognitive training programs have been reported as mildly beneficial for compensating memory difficulties in MCI. Controlling for vascular risk factors (high blood pressure, hyper- cholesterolemia, diabetes mellitus) may be a benefit preventive method for those MCI cases underlying vascular pathology. Currently, sensitive tools (imaging techniques or biomarkers) are not available for MCI screening in the general population. In primary care setting, clinicians should maintain a high suspicion for subjective cognitive complaints and should cor- roborate these complaints with collateral information whenever

more severe for age and less education. The main differentiation between MCI and Alzheimer’s disease resides in the lack of functional impairment in MCI. Course and Prognosis The typical rate at which MCI patients progress to Alzheim- er’s disease is 10 to 15 percent per year and is associated with Figure 21.6-3 Cognitive continuum showing the overlap in the boundary between normal aging and the mild cognitive impairment and Alzheimer’s disease. (Reprinted with permission from Petersen RC, ed. Mild Cognitive Impairment: Aging to Alzheimer’s Disease . New York: Oxford University Press, 2003.)

Table 21.6-3 Treatment Trials for Mild Cognitive Impairment

Patients (n)

Study

Duration Primary Outcome Results

OBS

Sponsor

Donepezil +

769

3 years

Conversion to AD Partially positive (reduced risk of developing

Amnestic MCI status and the presence of APOE4 allele– predictive of rate of progression to AD

ADCS

vitamin E (Thall et al., 1999)

AD in the active arm group for the first 12 months)

Donepezil

269

24 weeks

ADAS-Cog total score; NYU PTIR

Negative

Positive results in

Pfizer (The

(Salloway et al., 2004)

secondary outcome measures (ADAS- Cog13)

Donepezil “401” Study Group)

Rivastigmine

1,018 48 months Conversion to AD Negative

Novartis

(Feldman et al., 2007)

Galantamine

2,048 2 years

Progression of CDR score (from .5 to 1)

Negative

Attention assessed by DSST favored

Johnson & Johnson

(Johnson and Johnson, 2004)

galantamine in both studies

Rofecoxib (Thall et al., 2005)

1,457 3–4 years

Conversion to AD Negative

Primary outcome favored placebo while secondary outcomes (ADS- cog, CDR) did not

Merck

differentiate between rofecoxib and placebo

Piracetam

675

12 months Composite score extracted from eight tests

Negative

UCB Pharma

AD, Alzheimer’s disease; ADCS, Alzheimer Disease Cooperative Study; CDR, Clinical Dementia Rating; DSST, Digit Symbol Substitution test; MCI, mild cognitive impairment; MCI, mild cognitive impairment; NYU PTIR, NewYork University Paragraph Test Immediate Recall.