At the patient's first presentation with cognitive changes, laboratory testing may be useful for evaluating reversible causes of cognitive impairment, such as delirium.2 Tests should include a CBC, complete metabolic panel, ESR, and thyroid-stimulating hormone. Other tests that may be indicated based on the patient's history include measures of serum vitamin B12, RPR/VDRL, HIV, and Lyme disease. Comorbid conditions such as diabetes, hyperlipidemia, and hypertension should be fully treated, and cognitive function should then be reassessed.
In the setting of neurologic or cognitive changes, neuroimaging may be helpful in assessing MCI and dementia. Brain MRI can demonstrate whole brain atrophy, increased relative ventricular volume, or atrophy of specific regions such as the frontal lobes, hippocampus, and entorhinal cortex, particularly in AD.2,3 Hippocampal and entorhinal cortex volumes may be affected in patients with amnestic MCI before AD develops.10 In addition, vascular pathology that may be associated with vascular dementia may be apparent on MRI.2 When available, positron emission tomography may be useful for assessing brain region functional activity3 as well as for quantifying brain amyloid distribution.11
Several CSF biomarkers for AD are being studied for their predictive capability and may be available in the future.2 In AD, CSF tau and phosphorylated tau protein concentrations increase and amyloid BETA-42 decrease compared with normal controls.10,12 Patients who have MCI that has progressed to AD have increased CSF tau concentrations, whereas CSF tau concentrations remain low in patients with MCI that has not progressed to AD.10 The genetic marker apolipoprotein E4 (ApoE4) allele is associated with increased risk for developing AD, and screening for this allele may assist in prediction of disease progression.2,5 Mutations in genes for amyloid precursor proteins presenilin 1 and presenelin 2 are also associated with earlier symptom presentation and their detection.
HOW ARE MCI AND DEMENTIA TREATED?
MCI has multiple contributing causes, and there is no single effective treatment. The Alzheimer's Disease Cooperative Study demonstrated the cholinesterase inhibitor donepezil (Aricept, generics) to be effective at reducing risk for progressing from MCI to AD over the first 12 months of the study and was particularly effective in ApoE4 carriers; however, no significant benefits were noted at the end of the 3-year study.4 In two separate trials, the cholinesterase inhibitor galantamine (Razadyne, generics) did not significantly slow progression from MCI to AD after 24 months and was associated with an increased death rate.4 Finally, the cholinesterase inhibitor rivastigmine (Exelon, generics) showed no significant benefits in conversion from MCI to AD after 4 years; however, mortality was not affected.4 Therefore, while not currently indicated for MCI, the cholinesterase inhibitors appear to be somewhat effective for delaying the cognitive changes associated with progression of MCI to dementia. Because of its association with an increased death rate, galantamine should be reserved for patients who do not tolerate donepezil or rivastigmine.
The N-methyl-D-aspartic acid receptor antagonist memantine (Namenda) was shown to have small but significant effects at improving cognition, behavior, and activities of daily living in patients with moderate to severe AD but not in those with vascular dementia for up to 6 months after initiating treatment.13 Reports on memantine's effectiveness in MCI are not presently available, and this medication is indicated only for patients with moderate to severe AD. Other proposed medical treatments, which have not demonstrated protective effects, include the cyclooxygenase inhibitor rofecoxib (Vioxx, withdrawn), vitamin E and other antioxidant nutrients, and omega 3 fatty acids.
Physical activity has been shown to improve multiple aspects of cognition, with the greatest effects on executive functions, even when activity is started later in life.14 Social and intellectual engagement are likewise beneficial14 and should be encouraged throughout the lifespan.
Clinicians should consider the social and familial impact of MCI, and particularly dementia, on patients and their support system. Patients and families should be referred to supportive social services to assist in meeting the escalating care requirements that follow progression to dementia. Clinicians should facilitate the patient's access to those services as a part of caring for the patient and family. JAAPA
This article was written by Gilbert A. Boissonneault, PhD, PA-C. Contributors included the other members and staff of CSAC 2009-2010: Daniel L. O'Donoghue, PhD, PA-C, Chair; Anthony E. Brenneman, MPAS, PA-C; Alison C. Essary, MHPE, PA-C; Michelle Lynn Heinan, EdD, PA-C; Marie-Michèle Léger, MPH, PA-C; and Thomas Moreau, PA-C, MS. The manuscript was edited by Sarah Zarbock, PA-C.
Acknowledgement: CSAC would like to thank Brandon Dennis, PsyD, of the University of Kentucky Sanders-Brown Center on Aging for helpful discussions on MCI neuropsychological testing.
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