Neurobiology of Delusions in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities.Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia

“…So, psychosis is prominent in AD and in determining brain-behavior correlates, neuroimaging literature has largely studied psychosis as a whole entity. However, compelling evidence supports the need to study delusions separate from hallucinations or psychosis and that delusions should also be subtyped into persecutory or misidentification for further study (Ismail et al, 2011). Our findings acknowledge the domination of delusions within psychosis in AD, as delusions are more prevalent than hallucinations.…”

Delusions Increase Functional Impairment in Alzheimer’s Disease

“…This is particularly the case given that the changes noted were independent of other cognitive measures of disease severity. In a recent review of this area, Ismail et al [33] suggest that AD patients with delusions differ from those without delusions in terms of genetics, neurotransmitters, neuropathology and clinical course. They suggest that in fact different delusional subtypes (misidentification delusions vs. persecutory delusions) may have different neural mechanisms.…”

Cognitive phenotype of psychotic symptoms in Alzheimer's disease: evidence for impaired visuoperceptual function in the misidentification subtype

“…Attempts to further categorise symptoms using factor analytical approaches have identified two broad subtypes (Cook et al ., 2003): a ‘paranoid’ subtype, which includes delusions of persecution and/or abandonment, and a ‘misidentification’ subtype, characterised by the presence of misidentification phenomena and/or hallucinations. Research into the phenotypic correlates of psychotic symptoms (predominantly delusions) has provided some evidence to support this classification (Ismail et al ., 2011; Reeves et al ., 2012), as the misidentification but not paranoid subtype has been associated with more marked AD (neurofibrillary tangle) pathology postmortem (Ferman et al ., 2013; Forstl et al ., 1994; Mukaetova‐Ladinska et al ., 1993) and more global cognitive deficits (indexed by lower mini‐mental state examination (MMSE) scores), in clinical studies (Perez‐Madrinan et al ., 2004; Reeves et al ., 2012). …”