Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis

Koppel, Jeremy; Goldberg, Terry E.; Gordon, M.S.; Huey, Edward D.; Davies, Peter; Keehlisen, Linda; Huet, Sara; Christen, Erica; Greenwald, Blaine S.

doi:10.1097/jgp.0b013e3182358921

Cited by 52 publications

(58 citation statements)

References 51 publications

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“…Our findings are consistent with previous studies that have reported increased cognitive and functional decline in psychotic AD patients as a whole [1–3, 42–44], and greater cognitive and functional deficits associated with hallucinations compared to delusions [6, 45, 46]. Delusions have been found to manifest earlier in the disease course than hallucinations, so it has been speculated that differences in cognitive ability dictates the form of psychosis: patients with milder cognitive decline tend to exhibit delusions while patients with more advanced cognitive impairment tend to exhibit hallucinations [46, 47].…”

Section: Discussionsupporting

confidence: 94%

Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease

Qian

Fischer

Schweizer

et al. 2018

CAR

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Background: Psychosis is a common phenomenon in Alzheimer’s disease (AD). The APOE ε4 allele is the strongest genetic risk factor for the development of AD, but it’s association with psychosis remains unclear. Objective: We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ε4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ε4, Lewy bodies, and psychosis. Methods: Data from the National Alzheimer’s Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ε4, as well as their interaction. Results: Psychosis and the presence of APOE ε4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ε4 on MMSE scores, with APOE ε4 negatively affecting patients with hallucinations-only psychosis. APOE ε4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. Conclusion: Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations—with or without delusions—conferred even greater deficits compared to patients with only delusions. The APOE ε4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ε4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.

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Section: Discussionsupporting

confidence: 94%

Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease

Qian

Fischer

Schweizer

et al. 2018

CAR

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“…22 Digit span has also been associated with psychosis itself, because poorer performance on digit span tasks was associated with psychotic symptoms in a study of AD and MCI. 10 In the current study, psychosis had a complex relationship with digit span tasks. On the Forward Digit Span task, this association was mediated by age, as younger ever psychotic subjects only had a more rapid decline in digit span performance than never psychotic subjects.…”

Section: Discussionmentioning

confidence: 98%

“…7e9 If the hypofrontality model is valid, this focal impairment may have a distinguishing cognitive signature separate from the psychiatric symptomatology. Recently, our group reported on an association between ADþP and impairment on one task of working memory, the digit span test, 10 which may represent the cognitive expression of hypofrontality in ADþP. Approaches to evaluating frontal function in vivo include both cognitive assessment on frontal tasks and functional neuroimaging comparing regional brain metabolism.…”

mentioning

confidence: 99%

Psychosis in Alzheimer’s Disease is Associated with Frontal Metabolic Impairment and Accelerated Decline in Working Memory: Findings from the Alzheimer's Disease Neuroimaging Initiative

Koppel¹,

Sunday²,

Goldberg³

et al. 2014

The American Journal of Geriatric Psychiatry

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“…Most studies find that delusions are more common among those AD patients with advanced cognitive deficits (1, 4, 5). Few studies have examined the relationship between delusional thoughts and memory deficits specifically (6) or the relationship between delusional thoughts and impaired insight. Two studies found a correlation between delusional thoughts and a lack of awareness of cognitive deficits in AD (7, 8).…”

Section: Objectivementioning

confidence: 99%

Neurobiology of Delusions, Memory, and Insight in Alzheimer Disease

Sultzer

Leskin

Melrose

et al. 2014

The American Journal of Geriatric Psychiatry

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Objectives Delusional thoughts are common among patients with Alzheimer’s disease (AD) and may be conceptually linked to memory deficits (cannot recall accurate information which fosters inaccurate beliefs) and poor insight (unable to appreciate the illogic of beliefs). This study’s goals were to examine the clinical associations among delusions, memory deficits, and poor insight, explore neurobiological correlates for these symptoms, and identify shared mechanisms. Design Cross sectional analysis. Setting VA Greater Los Angeles Healthcare System. Participants Eighty-eight outpatients with AD (mean MMSE 19.3). Measurements Delusional thoughts were assessed with the Neuropsychiatric Inventory. Level of inaccurate insight was assessed with the Neurobehavioral Rating Scale (NRS). Memory was assessed with the Mattis Dementia Rating Scale (DRS) memory subscale. 18F-FDG PET imaging was used to measure regional cortical metabolism. Relationships between clinical ratings and regional cortical metabolic activity (voxel-based) were assessed using SPM2. Results Patients with delusions had lower DRS memory subscale scores. NRS inaccurate insight scores were no different in those with and without delusions. Cortical metabolic activity was lower in the right lateral frontal cortex, orbitofrontal cortex, and bilateral temporal cortex in patients with delusions. Low cortical metabolic activity in the right lateral, inferior, and medial temporal cortex was associated with poorer memory. This region partially overlapped the region of hypometabolism associated with delusions. In contrast, low cortical metabolic activity in bilateral medial frontal cortex was associated with poor insight. Conclusions Delusions in AD are associated with dysfunction in specific frontal and temporal cortical regions. Delusions are partially clinically and neurobiologically linked to memory deficits but not to poor insight.

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Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis

Cited by 52 publications

References 51 publications

Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease

Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease

Psychosis in Alzheimer’s Disease is Associated with Frontal Metabolic Impairment and Accelerated Decline in Working Memory: Findings from the Alzheimer's Disease Neuroimaging Initiative

Neurobiology of Delusions, Memory, and Insight in Alzheimer Disease

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