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Abstract

Objective: To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease (AD) who are treated with a cholinesterase inhibitor (ChEI).
Methods: Patients with mild cognitive impairment (MCI) (12), mild AD (48), and moderate AD (24) (Global Deterioration Scale stages 3, 4, and 5) were randomized to receive psychosocial support plus cognitive-motor intervention (experimental group) or psychosocial support alone (control group). Cognitive-motor intervention (CMI) consisted of a 1-year structured program of 103 sessions of cognitive exercises, plus social and psychomotor activities. The primary efficacy measure was the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary efficacy measures were the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Geriatric Depression Scale. Evaluations were conducted at 1, 3, 6, and 12 months by blinded evaluators.
Results: Patients in the CMI group maintained cognitive status at month 6, whereas patients in the control group had significantly declined at that time. Cognitive response was higher in the patients with fewer years of formal education. In addition, more patients in the experimental group maintained or improved their affective status at month 12 (experimental group, 75%; control group, 47%; p = 0.017).
Conclusions: A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.

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Letters to the Editor
8 March 2005
Reply to Kavirajan
Javier Olazarán, Fundación Maria Wolff
Ruben Muñiz

As Dr. Kavirajan states, our paper has some methodological limitations which are already discussed in our article. Program attendance and lack of a dose effect are described in the Results ('Safety and Compliance' and last paragraph) whereas statistical and other limitations regarding study design are discussed in the final paragraph.

A completely blind assessment in non-pharmacological interventions is very difficult, if not impossible. Ideally, a mock intervention should have been designed and implemented but, even under those circumstances, the quality of blinding is questionable. [3] Kavirajan mentions that patients and caregivers could have mentioned issues related to cognitive-motor intervention during assessments. It is unlikely that a systematic bias could have been introduced because our evaluators were blind not only to patient group, but also to study design.

Since Alzheimer disease (AD) is a progressive and irreversible condition, lack of deterioration is gaining acceptance as a way of determining response in long-term trials. [4,5] As long as affective disturbances increase from mild cognitive impairment to more advanced dementia stages, defining response should also be adequate for the affective domain. [6]

The cognitive reserve concept does not predict a poorer cognitive performance in patients with higher educational attainment. Rather, cognitive reserve would allow better coping with AD pathology. For that reason, given a level of clinical severity, the underlying AD pathology would be more advanced in patients with more cognitive reserve. [7] These patients would be at their limit of compensating capacity and therefore would hardly benefit from the strategies given at the cognitive-motor sessions.

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8 March 2005
Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease
Harish C. Kavirajan, UCLA Geffen School of Medicine

We read the article by Olazaran et al with interest. [1] There are several problems with study design and data analysis:

1. The quality of the blinding is questionable. Most patients had MCI or mild dementia, and therefore presumably fair recall of recent events/activities. The patients themselves, not only caregivers, could have divulged group assignment to the blinded evaluators.

2. The control group lacked a social stimulation intervention so the modest benefits of CMI could be ascribed to nonspecific social stimulation effects, rather than specific properties of the CMI.

3. The CMI group was responsible for paying for treatment and attending frequent training sessions. Accordingly, differences in financial or psychosocial resources may have impacted differences in outcome.

4. "Mood responders" were defined as patients who maintain or improve their baseline GDS score. However, GDS depression scores were low in both groups, with means well below the cutoff for even mild depression. Lack of change or improvement in such subjects would not qualify as a response.

5. Instead using of a more conventional paired t-test, the authors treated data from each group at different points in time as though from different groups, suggesting that large within-subject variance may have reduced statistical significance with analysis of within-subject change. The unreliability of the MMSE for measuring short-term change is well known. [2]

6. Failure to adjust for multiple statistical analyses increased the probability of a type I error. The only justification offered is that such a correction would have increased the probability of a type II error.

7. The conclusions regarding behavioral benefits were based on comparisons of the mean scores on the ADRQL and NPI only at study endpoint, without controlling for baseline data. Hence, the differences between groups at endpoint may simply have reflected baseline differences in the two groups.

8. The authors failed to describe CMI program attendance. Besides demonstrating tolerability of the intervention, such data might suggest a dose-effect of treatment, which would bolster the case for an effect of CMI.

9. The explanation of the negative effect of education is not clear. The logic of the cognitive reserve hypothesis is inconsistent with the notion that higher levels of education could explain poorer performance on cognitive measures.

References

1. Olazaran J, Muniz R, Reisberg, B, et al. Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer's disease. Neurology 2004;63:2348-2353.

2. Clark, CM, Sheppard L, Fillenbaum GG, et al. Variability in Annual Mini-Mental State Examinations Score in Patients With Probable Alzheimer Disease. Arch Neurol. 1999;56:857-62.

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Published In

Neurology®
Volume 63Number 12December 28, 2004
Pages: 2348-2353
PubMed: 15623698

Publication History

Received: November 10, 2003
Accepted: August 31, 2004
Published online: December 28, 2004
Published in print: December 28, 2004

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Affiliations & Disclosures

J. Olazarán, MD, PhD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
R. Muñiz, BSc
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
B. Reisberg, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
J. Peña-Casanova, MD, PhD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
T. del Ser, MD, PhD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
A. J. Cruz-Jentoft, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
P. Serrano, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
E. Navarro, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
M. L. García de la Rocha, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
A. Frank, MD, PhD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
M. Galiano, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
Y. Fernández-Bullido, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
J. A. Serra, MD, PhD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
M. T. González-Salvador, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.
C. Sevilla, MD
From Fundación Maria Wolff (Drs. Olazarán and Serrano, and R. Muñiz), Madrid; Consulta de Neurología (Dr. Olazarán), CEP Hermanos Sangro, Madrid; Servicio de Neurología (Drs. Olazarán, Navarro, Galiano, and Fernández-Bullido) and Geriatría (Dr. Serra), Hospital Gregorio Marañón, Madrid, Spain; Silberstein Aging and Dementia Research Center (Dr. Reisberg), NYU School of Medicine Medical Center, New York, NY; Servicio de Neurología (Dr. Peña-Casanova), Hospital del Mar, Barcelona; Servicio de Neurología (Dr. del Ser), Hospital Severo Ochoa, Leganés; Unidad de Geriatría (Dr. Cruz-Jentoft), Hospital Ramón y Cajal, Madrid; Consulta de Neurología (Dr. Navarro), CEP Vicente Soldevilla, Madrid; Servicio de Neurología (Dr. García de la Rocha) and Psiquiatría (Dr. González-Salvador), Hospital Gómez Ulla, Madrid; Servicio de Neurología (Dr. Frank), Hospital la Paz, Madrid; Consulta de Neurología (Dr. Galiano and Fernández-Bullido), CEP Moratalaz, Madrid; and Servicio de Neurología (Dr. Sevilla), Hospital de la Princesa, Madrid, Spain.

Notes

Address correspondence and reprint requests to Dr. Rubén Muñiz, Director de Investigación, Fundación Maria Wolff, Cardenal Silíceo 14, 28002 Madrid, Spain; e-mail: [email protected]

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