Abstract
Introduction
There is evidence that neurofibrillary tangle (NFT) burden is associated with psychotic
symptoms in Alzheimer disease (AD). However, it is not clear whether this association
is direct or mediated through the increased cognitive impairment associated with NFTs.
Methods
We sought to determine whether the extended MAPT haplotype was associated with the worsening of delusions and hallucinations in a
combined cohort of 95 patients who participated in 2 clinical trials of treatment
with memantine.
Results
After controlling for baseline dementia severity, exposure to memantine, and antipsychotics,
analysis shows that carriers of at least one H2 allele had a 5.4-fold (P = .03) increased risk of worsening hallucinations. There was some evidence of association
with worsening delusions but only in analysis by allele.
Conclusion
These results are the first to indicate that the H2 allele of the extended MAPT haplotype negatively affects the course of psychotic symptoms in AD independently
of disease severity. It will be important for future research to examine MAPT transcription in people with AD with and without psychotic symptoms to understand
the exact mechanisms underlying these findings.
Keywords
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References
Alzheimer's Disease International. Alzheimer's Disease International World Alzheimer Report. Available at: http://www.alz.co.uk/research/files/WorldAlzheimerReport.pdf. Accessed June 5, 2014.
- Treatment of behavioral and psychological symptoms of Alzheimer's disease.Curr Treat Options Neurol. 2012; 14: 113-125
- Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease.Am J Psychiatry. 1996; 153: 1438-1443
- The course of neuropsychiatric symptoms in dementia. Part I: Findings from the two-year longitudinal Maasbed study.Int J Geriatr Psychiatry. 2005; 20: 523-530
- A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease.Am J Geriatr Psychiatry. 2005; 13: 460-468
- Neuropsychiatric symptoms and the risk of institutionalization and death: The aging, demographics, and memory study.J Am Geriatr Soc. 2011; 59: 473-481
- Incidence of and risk factors for hallucinations and delusions in patients with probable AD.Neurology. 2000; 54: 1965-1971
- Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.BMJ. 1997; 314: 266-270
- Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis.Arch Gen Psychiatry. 2000; 57: 1165-1173
- Neuropathologic and neurochemical correlates of psychosis in primary dementia.Arch Neurol. 1991; 48: 619-624
- Neuropathological correlates of psychotic phenomena in confirmed Alzheimer's disease.Br J Psychiatry. 1994; 165: 53-59
- Tau phosphorylation is exaggerated in Alzheimer disease with psychosis.Am J Geriatr Psychiatry. 2013; 21: S80-S81
- The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts.Neurobiol Dis. 2007; 25: 561-570
- No association of psychosis in Alzheimer disease with neurodegenerative pathway genes.Neurobiol Aging. 2011; 32: 555.e9-555.e11
- Efficacy of memantine for agitation in Alzheimer’s dementia: A randomised double-blind placebo controlled trial.PLoS One. 2012; 7: e35185
- DNA from buccal swabs recruited by mail: Evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping.Behav Genet. 2003; 33: 67-72
- Association of an extended haplotype in the tau gene with progressive supranuclear palsy.Hum Mol Genet. 1999; 8: 711-715
- Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: A pooled analysis of 3 studies.J Clin Psychiatry. 2008; 69: 341-348
- The extended tau haplotype and the age of onset of dementia in Down syndrome.Dement Geriatr Cogn Disord. 2008; 26: 199-202
- Genetic association between APOE*4 and neuropsychiatric symptoms in patients with probable Alzheimer's disease is dependent on the psychosis phenotype.Behav Brain Funct. 2012; 8: 62
- Association between tau H2 haplotype and age at onset in frontotemporal dementia.Arch Neurol. 2005; 62: 1419-1422
- Association of the tau haplotype H2 with age at onset and functional alterations of glucose utilization in frontotemporal dementia.Am J Psychiatry. 2007; 164: 1577-1584
- Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease.Am J Psychiatry. 2003; 160: 341-349
- The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer's disease.J Neuropsychiatry Clin Neurosci. 1995; 7: 476-484
Article info
Publication history
Published online: October 08, 2014
Footnotes
The authors declare no conflicts of interest.
Both the MAIN-AD (ISRCTN68407918) and MAGD (ISRCTN24953404) clinical trials were funded by Lundbeck Plc.
Identification
Copyright
© 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
