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Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.
Clin Ther 2006; 28(7):991-1001CT

Abstract

BACKGROUND

There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk.

OBJECTIVES

The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI.

METHODS

Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006.

RESULTS

Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development.

CONCLUSIONS

MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.

Authors+Show Affiliations

Department of Neurology and Alzheimer's Disease Center, Emory University School of Medicine, Atlanta, GA 30322, USA. allan.levey@emory.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

16990077

Citation

Levey, Allan, et al. "Mild Cognitive Impairment: an Opportunity to Identify Patients at High Risk for Progression to Alzheimer's Disease." Clinical Therapeutics, vol. 28, no. 7, 2006, pp. 991-1001.
Levey A, Lah J, Goldstein F, et al. Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease. Clin Ther. 2006;28(7):991-1001.
Levey, A., Lah, J., Goldstein, F., Steenland, K., & Bliwise, D. (2006). Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease. Clinical Therapeutics, 28(7), pp. 991-1001.
Levey A, et al. Mild Cognitive Impairment: an Opportunity to Identify Patients at High Risk for Progression to Alzheimer's Disease. Clin Ther. 2006;28(7):991-1001. PubMed PMID: 16990077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease. AU - Levey,Allan, AU - Lah,James, AU - Goldstein,Felicia, AU - Steenland,Kyle, AU - Bliwise,Donald, PY - 2006/05/08/accepted PY - 2006/9/23/pubmed PY - 2006/10/13/medline PY - 2006/9/23/entrez SP - 991 EP - 1001 JF - Clinical therapeutics JO - Clin Ther VL - 28 IS - 7 N2 - BACKGROUND: There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. OBJECTIVES: The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. METHODS: Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. RESULTS: Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development. CONCLUSIONS: MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/16990077/Mild_cognitive_impairment:_an_opportunity_to_identify_patients_at_high_risk_for_progression_to_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(06)00168-8 DB - PRIME DP - Unbound Medicine ER -