A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease

Eustace, A.; Coen, Robert F.; Walsh, Cathal; Cunningham, Conal; Walsh, Judy; Coakley, Davis; Lawlor, Brian A.

doi:10.1002/gps.736

Cited by 95 publications

(103 citation statements)

References 24 publications

(38 reference statements)

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“…Longitudinal studies using assessment scales other than the NPI demonstrate heterogeneity in the course of symptoms and that NPS may arise at any stage of dementia. However, agitation seems to be the most persistent symptom and shows an increasing severity with disease progression in a majo-rity of the studies, whereas the persistence of psychosis and depression shows greater variability (27)(28)(29)(30). It should be noted that apathy was investigated rarely in these studies.…”

Section: Nps In Persons With Dementia Attending Outpatient Clinicsmentioning

confidence: 83%

The prevalence and the course of neuropsychiatric symptoms in patients with dementia

Bergh¹,

Selbæk²

2012

Nor J Epidemiol

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Dementia is prevalent in Norway and other countries and is hallmarked by a decline in memory and other cognitive abilities. In addition to cognitive decline, the vast majority of patients with dementia experience neuropsychiatric symptoms (NPS) such as depression, agitation, psychosis, apathy, or irritability. In this review, we describe the prevalence and the course of NPS in patients with dementia, referring to results of population-based studies, studies of outpatients, and studies of patients in long-term care. For a better comparison of the included studies and for clarification, we have included studies that have assessed NPS with the Neuropsychiatric Inventory (NPI). Overall, we found a high prevalence rate of NPS. At least one NPS (NPI > 0) was present in 56% to 98% of the patients and 62% to 84% of the patients had at least one clinically significant NPS (NPI > 3). The NPS with the highest prevalence rate were apathy, irritability, agitation, depression and anxiety; while delusion, hallucination, disinhibition, aberrant motor behavior and euphoria were the least frequent NPS.

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Section: Nps In Persons With Dementia Attending Outpatient Clinicsmentioning

confidence: 83%

The prevalence and the course of neuropsychiatric symptoms in patients with dementia

Bergh¹,

Selbæk²

2012

Nor J Epidemiol

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“…Previously, the presence of more severe noncognitive symptoms, such as elation, motor disturbances, hallucinations, delusions, and disinhibition, is described in conjunction with more advanced AD dementia. 2 Our sample suggests that this arc of noncognitive changes begins in preclinical AD dementia. Such a finding corroborates our previous study, which showed that depression scores and other behavioral symptoms monitored by the NPI-Q worsen faster among individuals with preclinical AD dementia at baseline as defined by CSF biomarkers.…”

mentioning

confidence: 79%

“…With progressive cognitive and functional decline in AD dementia, the presence of NPS is postulated to represent increased neurodegradation across neural systems. [2][3][4][5] Such NPS have been associated with worse prognosis, accelerated illness progression, increased use of services, and earlier institutionalization. 2 However, variable neuropsychiatric measures and clinical definitions have clouded the true incidence and progression of NPS in patients with AD.…”

mentioning

confidence: 99%

“Noncognitive” symptoms of early Alzheimer disease

Masters¹,

Morris²,

Roe³

2015

Neurology

159

117

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Objectives: To observe the natural time course of noncognitive symptoms before the onset of symptomatic Alzheimer disease dementia.Methods: Using the National Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March 2013, data from cognitively normal individuals who were aged 50 years or older at first visit and had subsequent follow-up were analyzed. Survival analyses were used to examine the development of particular symptoms relative to each other on the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire, and Geriatric Depression Scale, and to compare the development of individual symptoms for persons who did and did not receive a Clinical Dementia Rating (CDR) .0 (indicating abnormal cognition) during the follow-up period.Results: The order of symptom occurrence on the NPI-Q was similar for participants who remained at CDR 0 and for those who received a CDR .0 over the follow-up period, although the time to most NPI-Q symptoms was faster for participants who received a CDR .0 (p , 0.001). With the exception of memory, Geriatric Depression Scale symptoms reported by both CDR groups were similar. Conclusions:We found a significantly earlier presence of positive symptoms on the NPI-Q in cognitively normal patients who subsequently developed CDR .0. Among participants with no depression symptoms at baseline, results suggest that depressive symptoms may increase with aging regardless of incipient dementia. Such findings begin to delineate the noncognitive course of Alzheimer disease dementia in the preclinical stages. Future research must further elucidate the correlation between noncognitive changes and distinct dementia subtypes. The natural course of Alzheimer disease (AD) dementia includes hallmark functional and behavioral deficits in addition to cognitive decline. Alternately termed behavioral and psychological symptoms in dementia or neuropsychiatric symptoms (NPS), this heterogeneous array of noncognitive impairment affects an estimated 90% of patients with AD.1 Earlier studies have shown that with advancing cognitive decline in AD dementia, noncognitive symptoms include apathy, depression, agitation, and aggression, to psychosis. With progressive cognitive and functional decline in AD dementia, the presence of NPS is postulated to represent increased neurodegradation across neural systems.2-5 Such NPS have been associated with worse prognosis, accelerated illness progression, increased use of services, and earlier institutionalization.2 However, variable neuropsychiatric measures and clinical definitions have clouded the true incidence and progression of NPS in patients with AD.While noncognitive outcomes of AD after incident dementia are increasingly characterized, the relative time course of behavioral and functional deficits before onset of cognitive impairment in AD dementia has been rarely studied. Here, we examined the time course of noncognitive symptoms reported on the Functional Activities Questionnaire (FAQ), 6 Geriatric Depression

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“…It is also important to note that changes in the central cholinergic system in AD may also contribute to a variety of adverse behavioral symptoms (i.e., in addition to cognitive deficits) such as depression, aggressive behavior, psychosis, and overactivity (Minger et al, 2000). These so called "noncognitive" symptoms of AD increase caregiver burden, significantly raise the direct costs of care, and result in earlier institutionalization (reviewed Eustace et al, 2002). A number of studies now indicate that the standard therapy for cognitive dysfunction in AD (i.e., the acetylcholinesterase inhibitors) are associated with improvement in a number of behavioral symptoms including depression, psychosis, agitation, and a delay in nursing home placement (reviewed, Cummings, 2003).…”

Section: Cholinergic-based Therapeutic Strategies (Present and Futurementioning

confidence: 99%

The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development

Terry

Buccafusco

2003

J Pharmacol Exp Ther

991

607

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The cholinergic hypothesis was initially presented over 20 years ago and suggests that a dysfunction of acetylcholine containing neurons in the brain contributes substantially to the cognitive decline observed in those with advanced age and Alzheimer's disease (AD). This premise has since served as the basis for the majority of treatment strategies and drug development approaches for AD to date. Recent studies of the brains of patients who had mild cognitive impairment or early stage AD in which choline acetyltransferase and/or acetylcholinesterase activity was unaffected (or even up-regulated) have, however, led some to challenge the validity of the hypothesis as well as the rationale for using cholinomimetics to treat the disorder, particularly in the earlier stages. These challenges, primarily based on assays of post mortem enzyme activity, should be taken in perspective and evaluated within the wide range of cholinergic abnormalities known to exist in both aging and AD. The results of both post mortem and antemortem studies in aged humans and AD patients, as well as animal experiments suggest that a host of cholinergic abnormalities including alterations in choline transport, acetylcholine release, nicotinic and muscarinic receptor expression, neurotrophin support, and perhaps axonal transport may all contribute to cognitive abnormalities in aging and AD. Cholinergic abnormalities may also contribute to noncognitive behavioral abnormalities as well as the deposition of toxic neuritic plaques in AD. Therefore, cholinergic-based strategies will likely remain valid as one approach to rational drug development for the treatment of AD other forms of dementia. The Cholinergic HypothesisA variety of studies in humans indicate that basal forebrain and rostral forebrain cholinergic pathways including converging projections to the thalamus serve important functional roles in conscious awareness, attention, working memory, and a number of additional mnemonic processes (Perry et al., 1999).For more than 20 years, studies of the brains of those with advanced age and Alzheimer's disease (AD) have consistently found damage or abnormalities in these pathways (particularly basal forebrain projections) that appeared to correlate well with the level of cognitive decline. As a result, the so-called "cholinergic hypothesis" was developed, which essentially states that a loss of cholinergic function in the central nervous system contributes significantly to the cognitive decline associated with advanced age and AD (reviewed, Bartus, 2000). Extensive literature from animal experiments supports the human data described above. In fact, the importance of cholinergic function in the brain to learning and memory was first recognized more than 30 years ago after cholinergic antagonists (specifically antimuscarinic agents) were found to impair memory in rats (Deutsch, 1971). Considerable additional evidence now supports this early work, and antimuscarinic agents such as scopolamine and atropine have been shown to impair memory

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A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease

Cited by 95 publications

References 24 publications

The prevalence and the course of neuropsychiatric symptoms in patients with dementia

The prevalence and the course of neuropsychiatric symptoms in patients with dementia

“Noncognitive” symptoms of early Alzheimer disease

The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development

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