Cognitive effects of atypical antipsychotics in patients with Alzheimer's disease and comorbid psychiatric or behavioral problems: A retrospective study

College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Clinical Therapeutics (Impact Factor: 2.73). 10/2006; 28(10):1695-700. DOI: 10.1016/j.clinthera.2006.10.008
Source: PubMed


In addition to cognitive decline, 30% to 40% of patients with Alzheimer's disease (AD) experience concomitant psychiatric and behavioral complications, such as hallucinations, delusions, and aggression. Atypical antipsychotics (AAs) are used to treat psychosis and aggressive behaviors in these patients; however, data regarding their early effects on cognition are conflicting. Based on a literature search, the cognitive effects of long-term treatment with AAs in outpatients with AD have not been studied.
The aim of this study was to describe and compare the rate of cognitive decline with longterm AA use in adult patients with AD receiving concomitant treatment with cholinesterase inhibitors.
This study was conducted at the Department of Neurology, The Ohio State University, Columbus, Ohio. Data were collected from the charts of adult outpatients who (1) received care at Memory Disorders Clinic, Columbus, Ohio, between April 2003 and June 2005; (2) were aged > or =55 years with a diagnosis of mild to severe definite or probable AD; (3) received an AA for > or =6 months or did not receive any AA; and (4) received a cholinesterase inhibitor during the entire evaluation period. Cognitive function, as measured using the Mini-Mental State Examination (MMSE), was compared between those who received AA treatment and those who did not. The end point was the rate of decline in cognitive function, defined as annualized change in mean MMSE score from baseline to the end of follow-up.
Ninety-two outpatients were included in the final analysis (67 women, 25 men; mean age, 72.4 years). Thirty-four patients received treatment with an AA for 6 > or =months (mean duration of treatment, 421 days) and 58 did not receive any AA treatment. Quetiapine (mean dose, 67 mg/d) was prescribed to 28 (82 %) of the patients receiving an AA. The AAs were prescribed for psychosis (15 [44%] patients), psychosis/agitation (11 [32%]), and agitation/aggression (8 [24%]). The baseline mean MMSE scores in patients receiving and not receiving an AA were 14.65 and 17.88, respectively (P = 0.021), with mean (SD) annual rates of cognitive decline of 3.03 (1.84) and 2.24 (1.27), respectively (P = NS).
The results from this retrospective study of data from a small, selected group of outpatients with AD did not find a significant difference in the rate of cognitive decline between those who received an AA for > or =6 months and those who did not.

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    • "As AD progresses, a number of neuropsychiatric symptoms, including depression and anxiety, are exhibited [21]. Quetiapine effectively alleviates psychoses in AD [2] [22]. As an adjunctive to traditional therapy, quetiapine has been shown to be a useful treatment in patients with generalized anxiety disorder (GAD) or traditional treatment-resistant GAD [23]. "
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    ABSTRACT: Quetiapine, an atypical antipsychotic drug, is effective in treating the behavioral and psychological symptoms in Alzheimer's disease (AD). However, it is presently unclear whether quetiapine has beneficial effects on memory and whether the effects of quetiapine on psychological symptoms are associated with its effect on memory in AD. The present study was designed to examine the effect of chronic administration of quetiapine on the conditioned (generalized) anxiety that is related to learning experience of open arm exposure in the elevated T-maze (ETM) test in an amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. In a 2nd experiment, the effect of quetiapine on memory per se was investigated in a Y-maze test in AD mice. Non-transgenic and transgenic mice were treated with quetiapine in drinking water from the age of 2 months. After continuous treatment with quetiapine (5 mg/kg/day) for 10 months, mice were tested for conditioned anxiety on the ETM task. After ETM testing, the expression of brain-derived neurotrophic factor (BDNF), a neuroprotective protein, was examined by immunohistochemistry in the basolateral amygdala (BLA) and hippocampus. In the 2nd experiment, the effect of quetiapine (2.5 or 5 mg/kg/day) on the short-term memory in AD mice was tested in a Y-maze test. After 10 months of administration, quetiapine prevented the decrease of conditioned anxiety and cerebral BDNF in AD mice. In addition, quetiapine also prevented memory impairment in the Y-maze test in AD mice. These findings suggest that the therapeutic mechanism of quetiapine on anxiety in AD may be associated with its beneficial effect on memory and its neuroprotective effect on cerebral BDNF expression.
    Current Alzheimer research 08/2012; 10(2). DOI:10.2174/1567205011310020010 · 3.89 Impact Factor
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    • "sedatives, antidepressants and antipsychotics) and cognition in older persons with dementia have found inconsistent results. Some studies show that Alzheimer's disease (AD) patients who were given antipsychotics showed the same rate of cognitive decline as those who were not (Caballero et al., 2006; Livingston et al., 2007). In contrast, other studies with AD patients have revealed positive (De Deyn et al., 2004) and negative effects (Kennedy et al., 2005) on global measures of cognitive functioning after treatment with antipsychotic medication. "
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    ABSTRACT: Most studies examining psychotropic medication use on cognition in older persons with dementia include measures of global cognitive function. The present study examined the relationship between different types of psychotropic medication and specific cognitive functions in older people with dementia. Two hundred and six institutionalized older adults with dementia (180 women, mean age 85 years) were administered neuropsychological tests. Psychotropic medication use was extracted from their medical status and categorized as: sedatives, antidepressants and antipsychotics. Analysis of covariance revealed that psychotropic consumers, and particularly those who used antipsychotics, performed worse on neuropsychological tests of executive/attentional functioning than non-consumers. There were no differences between consumers of other classes of psychotropic drugs and non-consumers. The number of psychotropic drugs used was inversely related to executive/attentional functioning. These findings show that in institutionalized older adults with dementia, specific impairment of cognitive function, i.e. executive/attentional impairments, are associated with antipsychotic medication use. Future longitudinal studies are recommended.
    International Psychogeriatrics 03/2009; 21(2):286-94. DOI:10.1017/S1041610209008552 · 1.93 Impact Factor
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    American Journal of Alzheimer s Disease and Other Dementias 05/2008; 23(2):125-31. DOI:10.1177/1533317507307961 · 1.63 Impact Factor
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