Clinical Features and Mortality in Patients with Early-Onset Alzheimer’s Disease

Samson, W. N.; Duijn, Cornelia M. van; Hop, W. C. J.; Hofman, Andrea

doi:10.1159/000117218

Cited by 55 publications

(54 citation statements)

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“…12 In this study we noted associations between tremor and functional decline and tremor and mortality, but the relationships did not reach significance in the adjusted models. Tremor in the present study was mostly associated with higher risk for cognitive decline.…”

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confidence: 56%

“…5 In addition, information about presence of motor signs in AD is important because they may predict cognitive [6][7][8][9] and functional 2,10 decline, institutionalization, 2,10 and death. [10][11][12][13][14][15][16] However, some reports failed to detect significant associations for cognition, 2,[17][18][19] function, 17,18,20 institutionalization, 20 or mortality. 21,22 Many factors contribute to the variability in reported associations between motor signs and AD outcomes.…”

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confidence: 99%

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Man-in-the-barrel syndrome caused by a pontine lesion

Paulin¹,

Seze²,

Wyremblewski³

et al. 2005

Neurology

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Abstract-Objective:To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD). Methods: A total of 533 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination Յ 20/57 [‫ف‬MMSE Յ 10/30]), functional endpoint (Blessed Dementia Rating Scale Ն 10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance. Results: A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes. Conclusions: Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.

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confidence: 56%

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confidence: 99%

Man-in-the-barrel syndrome caused by a pontine lesion

Paulin¹,

Seze²,

Wyremblewski³

et al. 2005

Neurology

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“…One study found that nursing home residents who later died had displayed more verbal agitation than those who survived during the same follow-up period (t ¼ 2.03, effect size 0.51) (Allen et al, 2005); however, another study reported that the association between mortality and agitation in dementia disappeared on multivariate analysis (Bowen et al, 1996). Likewise, some investigations have demonstrated an association between psychosis of dementia and increased mortality (Wilson et al, 2006), whereas other researchers have not found such a relationship (Samson et al, 1996;Rosen and Zubenko, 1991).…”

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ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Jeste

Blazer

Casey

et al. 2007

Neuropsychopharmacol

329

273

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In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6-1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/ or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.

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Motor signs predict poor outcomes in Alzheimer disease

Scarmeas¹,

Albert²,

Brandt³

et al. 2005

Neurology

177

127

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Objective-To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD). Methods-A total of 533 patients with AD at early stages (mean Folstein Mini-Mental StateExamination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination ≤ 20/57 [∼MMSE ≤ 10/30]), functional endpoint (Blessed Dementia Rating Scale ≥ 10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance.Results-A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes.Conclusions-Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.Motor signs are commonly observed in Alzheimer disease (AD). [1][2][3][4] Because their exact mechanism and anatomic location of origin is not clear, in this article we use the term motor Address correspondence and reprint requests to Dr. Nikolaos Scarmeas, Columbia University Medical Center, 622 West 168th street, PH 19th floor, New York, NY 10032; ns257@columbia.edu. NIH Public Access Author ManuscriptNeurology. Author manuscript; available in PMC 2011 January 27. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript signs to refer to what is usually described in the literature as extrapyramidal signs or parkinsonian signs or parkinsonism.As compared to patients with AD without motor signs, patients with AD with motor signs have higher annual total cost of care. 5 In addition, information about presence of motor signs in AD is important because they may predict cognitive 6-9 and functional 2,10 decline, institutionalization, 2,10 and death. [10][11][12][13][14][15][16] However, some reports failed to d...

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Clinical Features and Mortality in Patients with Early-Onset Alzheimer’s Disease

Cited by 55 publications

References 0 publications

Man-in-the-barrel syndrome caused by a pontine lesion

Man-in-the-barrel syndrome caused by a pontine lesion

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Motor signs predict poor outcomes in Alzheimer disease

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