Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer’s Dementia Are Frequently Below the Recommended Levels

Mild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI. To estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study. Cross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study. A total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia. Prevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms. Of the 682 individuals with dementia or MCI, 43% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29% rated as clinically significant) with depression (20%), apathy (15%), and irritability (15%) being most common. Among the dementia participants, 75% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62% were clinically significant); 55% (n = 199) reported 2 or more and 44% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36%), depression (32%), and agitation/aggression (30%). Eighty percent of dementia participants (n = 233) and 50% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4% vs 1%; P =.02). Neuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.

Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.

The present study was designed to determine which of the memory tasks included in the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological battery best differentiate patients with early Alzheimer's disease from cognitively normal elderly control subjects and also best distinguish between the various levels of severity of the dementia process. A sample of CERAD patients with Alzheimer's disease was stratified by disease severity into those with mild, moderate, or severe dementia and matched with control subjects for sex, age, and education. Using multivariate procedures and cutting scores, the efficacy of each memory measure in distinguishing between these groups and control subjects was determined. The test for delayed recall was found to be the best overall discriminatory measure. The other tests of memory, ie, immediate recall, intrusion errors, and recognition memory, had poor overall discriminability. None of the CERAD memory measures were found to be particularly powerful in staging the severity of dementia. These findings suggest that tests for delayed recall may be particularly useful in the early detection of Alzheimer's disease and should be considered in screening batteries for dementia in community surveys.