Predicting Disease Progression in Alzheimer's Disease: The Role of Neuropsychiatric Syndromes on Functional and Cognitive Decline

Palmer, Katie; Lupo, F.A.; Perri, Roberta; Salamone, Giovanna; Fadda, Lucia; Caltagirone, Carlo; Musicco, Massimo; Cravello, Luca

doi:10.3233/jad-2010-101836

Cited by 55 publications

(51 citation statements)

References 40 publications

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“…Health outcome data from such large longitudinal studies can provide important real-world information on disease progression and associated resource use and costs, although available definitions of progression in the AD literature all vary considerably in their sensitivity [18, 19, 20, 21, 22, 23, 24, 25, 26] given considerable heterogeneity in individual rates of progression among patients with AD. A number of studies have characterized cognitive decline in patients with AD using Mini-Mental State Examination (MMSE) [27] scores, but there is little consensus on what magnitude or rate of decline constitutes an appropriate threshold for decline.…”

Section: Introductionmentioning

confidence: 99%

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

Jones

Lebrec

Kahle-Wrobleski

et al. 2017

Dement Geriatr Cogn Disord Extra

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Background/Aims: We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Methods: Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Results: Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Conclusion: Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia.

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Section: Introductionmentioning

confidence: 99%

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

Jones

Lebrec

Kahle-Wrobleski

et al. 2017

Dement Geriatr Cogn Disord Extra

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“…One of the earliest and most common neuropsychiatric symptoms in Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) is apathy, characterized by a loss of interest, motivation and goal-oriented behavior, as well as social withdrawal [1–15]. Apathy has been found to predict progression from normal cognition to MCI [16] and from MCI to AD dementia, as well as global functional decline and cognitive decline in cognitively normal (CN) elderly [17–21].…”

Section: Introductionmentioning

confidence: 99%

The Apathy Evaluation Scale: A Comparison of Subject, Informant, and Clinician Report in Cognitively Normal Elderly and Mild Cognitive Impairment

Guercio

Donovan

Munro

et al. 2015

JAD

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Background Apathy is a common neuropsychiatric symptom in Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI). Detecting apathy accurately may facilitate earlier diagnosis of AD. The Apathy Evaluation Scale (AES) is a promising tool for measurement of apathy in prodromal and possibly preclinical AD. Objective To compare the three AES sub-scales—subject-reported (AES-S), informant-reported (AES-I), and clinician-reported (AES-C)—over time in individuals at risk for AD due to MCI and advanced age (cognitively normal [CN] elderly). Methods Mixed effects longitudinal models were used to assess predictors of score for each AES sub-scale. Cox proportional hazards models were used to assess which AES sub-scales predict progression from MCI to AD dementia. Results Fifty seven MCI and 18 CN subjects (ages 53–86) were followed for 1.4±1.2 years and 0.7±0.7 years, respectively. Across the three mixed effects longitudinal models, the common findings were associations between greater apathy and greater years in study, a baseline diagnosis of MCI (compared to CN), and male sex. CN elderly self-reported greater apathy compared to that reported by informants and clinicians, while individuals with MCI under-reported their apathy compared to informants and clinicians. Of the three sub-scales, the clinician-reported AES (AES-C) best predicted transition from MCI to AD dementia. Conclusion In a sample of CN elderly and elderly with MCI, apathy increased over time, particularly in men and those with MCI. Self-reported AES scores may be more sensitive than informant and clinician-report when subjects are CN, but less reliable if subjects have MCI. Moreover, the clinician-reported AES sub-scale predicted progression from MCI to AD dementia.

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“…The burden of Alzheimer’s disease (AD) is compounded by neuropsychiatric symptoms (NPS) which occur in almost all patients [1, 2], and are usually persistent [3], NPS are associated with accelerated cognitive and functional decline [4, 5], worse quality of life [6, 7], earlier institutionalization [8–10], and accelerated mortality [10, 11]. Depression, apathy, anxiety, agitation and irritability are the most commonly observed NPS [2, 12].…”

Section: Introductionmentioning

confidence: 99%

Latent Classes of Neuropsychiatric Symptoms in NACC Controls and Conversion to Mild Cognitive Impairment or Dementia

Leoutsakos

Forrester

Lyketsos

et al. 2015

JAD

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Background A number of studies have linked neuropsychiatric symptoms to increase risk of dementia. Objective To determine if risk of conversion to mild cognitive impairment or dementia among healthy controls varied as a function of their pattern of neuropsychiatric symptoms. Method We studied individuals in the National Alzheimer Coordinating Center dataset collected from 34 Alzheimer Disease Centers between 2005 and 2013. The analysis included 4,517 volunteers who were ≥ 60 years old, cognitively normal, and had complete Neuropsychiatric Inventory data at their baseline visit, and had at least one follow-up. We used latent class analysis to identify 4 classes based on patterns of NPI symptoms. We used a cox proportional hazards model to determine if time to MCI or dementia varied by baseline latent class membership. Results We identified 4 latent classes of neuropsychiatric symptoms: irritable, depressed, complex (depression, apathy, irritability and nighttime behaviors) and asymptomatic. 873 participants converted to MCI or dementia. Hazard ratios for conversion by class were 1.76 (95% CI: 1.34, 2.33) for the irritable class, 3.20 (95% CI: 2.24, 4.58) for the complex class, and 1.90 (95% CI: 1.49, 2.43) for the depressed class, with the asymptomatic class as the reference. Conclusions Membership in all 3 symptomatic classes was associated with greater risk of conversion to MCI or dementia; the complex class had the greatest risk. Different patterns of neuropsychiatric symptoms may represent different underlying neuropathological pathways to dementia. Further work imaging and pathology research is necessary to determine if this is the case.

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Predicting Disease Progression in Alzheimer's Disease: The Role of Neuropsychiatric Syndromes on Functional and Cognitive Decline

Cited by 55 publications

References 40 publications

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

The Apathy Evaluation Scale: A Comparison of Subject, Informant, and Clinician Report in Cognitively Normal Elderly and Mild Cognitive Impairment

Latent Classes of Neuropsychiatric Symptoms in NACC Controls and Conversion to Mild Cognitive Impairment or Dementia

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