Predictors of Mortality and Institutionalization in Alzheimer Disease Patients 1 Year after Discharge from an Alzheimer Dementia Unit

Bianchetti, Angelo; Scuratti, Alberto; Zanetti, Orazio; Binetti, Giuliano; Frisoni, Giovanni B.; Magni, Eugenio; Trabucchi, Marco

doi:10.1159/000106930

Cited by 90 publications

(88 citation statements)

References 21 publications

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“…Use of home health services has been strongly associated with impairment in ADL, but not in cognition, among care recipients with AD [43] and thus might serve as an indicator of a loss of functional capacities, an important predictor of increased mortality in dementia [44,45]. Consistently, we observed that deterioration in basic ADL was an independent predictor of shorter survival in the multivariate models.…”

Section: Discussionsupporting

confidence: 83%

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

Wattmo¹,

Londos²,

Minthon³

2015

Dement Geriatr Cogn Disord

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Background/Aims: Factors including rate of disease progression, different aspects of cholinesterase inhibitor (ChEI) treatment, and use of community-based services might affect the longitudinal outcome of Alzheimer's disease (AD). Whether these factors alter life expectancy in AD is unclear. We therefore examined the association between long-term ChEI therapy and survival. Methods: The present study included 1,021 patients with a clinical diagnosis of AD and a Mini-Mental State Examination score of 10-26 at baseline from a 3-year, prospective, multicenter study of ChEI therapy in clinical practice. The relationship of potential predictors with mortality was analyzed using Cox regression models. Results: After up to 16 years of follow-up, 841 (82%) of the participants had died. In the Alzheimer's Disease Assessment Scale-cognitive subscale, a mean decline of ≥4 points/year or ≥2 points/year on the Physical Self-Maintenance Scale was a risk factor for an earlier death. In the multivariate models, longer survival was associated with higher ChEI dose and longer duration of treatment. Users of community-based services at baseline exhibited a 1-year shorter mean life expectancy than nonusers. Conclusion: A longer survival time can be anticipated for AD patients with slower deterioration who receive and tolerate higher ChEI doses and a longer duration of treatment.

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Section: Discussionsupporting

confidence: 83%

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

Wattmo¹,

Londos²,

Minthon³

2015

Dement Geriatr Cogn Disord

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“…Furthermore, when patients with long-term neurological illnesses have disrupted sleep, this becomes a problem not only for the patient but also for their carers (Bianchetti et al, 1995;Van Someren, 2000). The pronounced increase in nighttime activity of both carers and HD patients suggests that more attention should be paid to the management of the sleep disorder in HD.…”

Section: Discussionmentioning

confidence: 99%

“…When patients with long-term neurological illnesses have disrupted sleep, this becomes a problem not only for the patient but also for their carers (Bianchetti et al, 1995;Van Someren, 2000). Identification of its origin is essential to rational management of these diseases and should also provide novel insights into the nature of the neurodegenerative process.…”

Section: Introductionmentioning

confidence: 99%

Disintegration of the Sleep-Wake Cycle and Circadian Timing in Huntington's Disease

Morton¹,

Wood²,

Hastings³

et al. 2005

J. Neurosci.

375

295

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Sleepdisturbancesinneurologicaldisordershaveadevastatingimpactonpatientandcareralike.However,theirpathologicaloriginisunknown.Here we show that patients with Huntington's disease (HD) have disrupted night-day activity patterns. This disruption was mirrored in a transgenic model of HD (R6/2 mice) in which daytime activity increased and nocturnal activity fell, eventually leading to the complete disintegration of circadian behavior. The behavioral disturbance was accompanied by marked disruption of expression of the circadian clock genes mPer2 and mBmal1 in the suprachiasmatic nuclei (SCN), the principal circadian pacemaker in the brain. The circadian peak of expression of mPer2 was prematurely truncated, and the mRNA levels of mBmal1 were attenuated and failed to exhibit a significant circadian oscillation. Circadian cycles of gene expression in the motor cortex and striatum, markers of behavioral activation in wild-type mice, were also suppressed in the R6/2 mice, providing a neural correlate of the disturbed activity cycles. Increased daytime activity was also associated with reduced SCN expression of prokineticin 2, a transcriptional target of mBmal1 encoding a neuropeptide that normally suppresses daytime activity in nocturnal mammals. Together, these molecular abnormalities could explain the pathophysiological changes in circadian behavior. We propose that circadian sleep disturbances are an important pathological feature of HD, that they arise from pathology within the SCN molecular oscillation, and that their treatment will bring appreciable benefits to HD patients.

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“…Nevertheless, in our opinion, treating disrupted sleep in long-term neurologically ill patients is important, because a quiet night sleep for the patient would also benefit the patient's partner or the caregiver. In Alzheimer's disease, the sleep disturbances are a major factor for decision of institutionalization of the patients (Bianchetti et al, 1995;Hatfield et al, 2004). Thus, in HD, focused management of disturbed sleep may also mean the postponement of the institutionalization of HD patients.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Imposition of Sleep Slows Cognitive Decline and Reverses Dysregulation of Circadian Gene Expression in a Transgenic Mouse Model of Huntington's Disease

Pallier¹,

Maywood²,

Zheng³

et al. 2007

J. Neurosci.

188

138

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Transgenic R6/2 mice carrying the Huntington's disease (HD) mutation show disrupted circadian rhythms that worsen as the disease progresses. By 15 weeks of age, their abnormal circadian behavior mirrors that seen in HD patients and is accompanied by dysregulated clock gene expression in the circadian pacemaker, the suprachiasmatic nucleus (SCN). We found, however, that the electrophysiological output of the SCN assayed in vitro was normal. Furthermore, the endogenous rhythm of circadian gene expression, monitored in vitro by luciferase imaging of organotypical SCN slices removed from mice with disintegrated behavioral rhythms, was also normal. We concluded that abnormal behavioral and molecular circadian rhythms observed in R6/2 mice in vivo arise from dysfunction of brain circuitry afferent to the SCN, rather than from a primary deficiency within the pacemaker itself. Because circadian sleep disruption is deleterious to cognitive function, and cognitive decline is pronounced in R6/2 mice, we tested whether circadian and cognitive disturbances could be reversed by using a sedative drug to impose a daily cycle of sleep in R6/2 mice. Daily treatment with Alprazolam reversed the dysregulated expression of Per2 and also Prok2, an output factor of the SCN that controls behavioral rhythms. It also markedly improved cognitive performance of R6/2 mice in a two-choice visual discrimination task. Together, our data show for the first time that treatments aimed at restoring circadian rhythms may not only slow the cognitive decline that is such a devastating feature of HD but may also improve other circadian gene-regulated functions that are impaired in this disease.

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Predictors of Mortality and Institutionalization in Alzheimer Disease Patients 1 Year after Discharge from an Alzheimer Dementia Unit

Cited by 90 publications

References 21 publications

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

Disintegration of the Sleep-Wake Cycle and Circadian Timing in Huntington's Disease

Pharmacological Imposition of Sleep Slows Cognitive Decline and Reverses Dysregulation of Circadian Gene Expression in a Transgenic Mouse Model of Huntington's Disease

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