08 cortes/c
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
RECENT DATA ON THE NATURAL HISTORY OF ALZHEIMER'S DISEASE
RECENT DATA ON THE NATURAL HISTORY OF ALZHEIMER'S DISEASE:
RESULTS FROM THE REAL.FR STUDY
F. CORTES, S. GILLETTE-GUYONNET, F. NOURHASHEMI, S. ANDRIEU, C. CANTET, B. VELLAS,
THE REAL.FR GROUP
Service de Médecine Interne et Gérontologie Clinique, Pavillon JP Junod, 170 avenue de Casselardit 31300 Toulouse (France) (F Cortes, S Gillette-Guyonnet, F Nourhashemi,
C Cantet, B Vellas) and Unité Inserm 558, 37 allée Jules Guesdes, 31000 Toulouse (France) (F Cortes, S Gillette-Guyonnet, F Nourhashemi, S Andrieu, C Cantet, B Vellas),
Correspondence and proofs to: Name: Cortes Frederic, Address : Service de médecine interne et gérontologie clinique, Service du Pr Vellas, Pavillon JP Junod, Hôpital La Grave-
Casselardit, 170 avenue de Casselardit31300 Toulouse cedex 9-France, Tel.: 33.5.61.77.76.06,Fax: 33.5.61.77.25.93, E-Mail :
[email protected]
Abstract: Objectives: This paper aims to present the changes observed in the evolution of Alzheimer's disease
(AD) in the cohort REAL.FR after one year by taking account new treatments and improved management.
Methods: Four hundred and ninety-eight patients recruited for the REAL.FR study were followed for one year
with a standardized case report filled for each patient every 6 months. Changes in the status of these patients were
evaluated on various levels: cognitive, functional, behavioural, global, nutritional, social, medical and caregiver
burden. Specific treatments were also recorded. Results: A high proportion of patients received specific treatment
for AD throughout the year (86%), mainly acetylcholinesterase inhibitors (AChEI) . As expected we observed
statistically significant changes in cognitive function (MMS : -1.93±3.74, p<0.0001 and ADAS-cog : +2.40±3.74,
p<0.0001), an overall loss of autonomy (ADL :-0.56±1.05, p<0.0001 and IADL : -1.00±1.46, p<0.0001),
worsening of behavioral disturbances (NPI : +1.85±14.83, p=0.0047) and a deterioration of general status (CDR-
SB : +1.63±2.55, p<0.0001). Even if the MNA score decreased not significantly, the loss was close to the
threshold of significativity (MNA : -0.31±3.07, p=0.0531). Conclusion: We observed a statistically significant
change for the worse in most parameters. However, it appears that this deterioration had been relatively slowed
by non-pharmacological management and the specific AD treatments. This resulted in stability or improvement
of the condition in 63.4% of patient at 1 year. The management proposed (including prescription of AChEI)
seemed to have a real impact on the course of the disease during this first year of follow-up.
degradation, leading to improvement of the patients' condition(8). In the course of AD, we should not overlook the progress
At the present time, Alzheimer's (AD) disease is the subject
achieved in patient management through better knowledge of
of numerous studies, but paradoxically concerning its natural
the disease and through the development of home help services.
history little information is available which takes into account
The REAL.FR study (Réseau sur la Maladie d'Alzheimer
the advent of new treatments and improved management.
Français)has been set up with the aim of studying the natural
Alzheimer's disease is known to be a progressive disease
history of AD by taking all these factors into account. This
characterised by gradual cognitive decline and loss of
project is a unique observatory, assessing through longitudinal
autonomy, leading to total dependence of the patient and the
follow-up in 16 Alzheimer centers in France the long-term
onset of behavioural disturbances (1) which sometimes have
impact and tolerance of treatments, modalities of use of
major effects on the life of the patient and of the caregiver.
services and of management of the sick elderly person, as well
These problems are the result of a neurodegenerative process
as predictors of admission to hospital or to an institution. This
which particularly affects the cholinergic system (2). Because
paper aims to present the changes observed in the cohort after 1
of the increasing importance of AD, efficient management of
year by analysing all these parameters and their influence on
patients must be initiated and so our present knowledge of the
the course of AD.
natural history of the disease must be improved. In particular, itis necessary to take account of the influence of the treatments
Material and methods
which have recently become available, with first of all the threedrugs indicated for mild to moderate forms of the disease:
The REAL.FR study is a prospective multicenter study
donepezil (Aricept), rivastigmine (Exelon) and galantamine
which has recruited throughout France, between 2000 and
(Reminyl). These have proved their efficacy and tolerability in
2002, 693 patients presenting AD according to the NINCDS-
clinical trials, where they were found to slow the progression of
ADRDA and DSM-IV criteria (9,10). The methodology of the
the disease by inhibiting acetylcholine degradation (3,4,5,6,7).
study has been described in detail elsewhere (11). Briefly, for
More recently, a new drug for the more severe forms of the
inclusion in the study, the patients had to present a mild to
disease has been developed: memantine (Ebixa) which acts as a
moderate form of the disease (score between 12 and 26 on the
non-specific NMDA receptor antagonist, maintaining
Mini-Mental State) (12), be ambulatory, living in their own
glutamatergic transmission and thus reducing neuronal
homes and cared for by a clearly identified caregiver. At
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
THE JOURNAL OF NUTRITION, HEALTH & AGING
inclusion, the patients underwent a full medical examination
weight in 12 months, improvement is an increase of 4 % or
(CT scan, thyroid tests). We excluded from the study patients
more of baseline weight and stable is a weight at 1 year
with severe AD, those who were institutionalized and those
equivalent to baseline weight ± 4 %. For the MNA:
with a concomitant disorder which could affect the short-term
deterioration is a change to poorer nutritional status (3
categories: normal nutritional status (score >23.5), at risk of
Data are collected prospectively every 6 months for 4 years
malnutrition (score 17-23.5) or malnutrition (score <17)),
during a visit in 1 of the 16 centers participating in the study. A
improvement is a change to better nutritional status and stable
standardized case report form is filled in for each patient by a
means no change from initial category. For the Zarit scale :
specially trained, multidisciplinary medical team. The data
deterioration is an increase in burden (4 categories: no or slight
collected include:
burden (score 0-20), mild to moderate burden (score 20-40),
1/ cognitive evaluation with administration of the MMS (12)
moderate to severe burden (score 40-60) or severe burden
and the cognitive subscale of the Alzheimer's Disease
(score > 60)), improvement is a change of category (lighter)
Assessment Scale (ADAS-cog) (13),
towards lesser burden and stable is no change from initial
2/ evaluation of the capacity to carry out the activities of
daily living, using the Activities of Daily Living scale (ADL)(14) and the Instrumental Activities of Daily Living scale
(IADL) (15) for the more complex activities,
3/ evaluation of behavioural disturbance with the
Overview of follow-up
Neuropsychiatric Inventory (NPI) (16).
During the first year of follow-up, 25 subjects died, 30
4/ overall evaluation using the Clinical Dementia Rating
entered an institution and 91 prematurely discontinued follow-
(CDR) (17) and Reisberg's Global Dementia Scale (GDS) (18).
up for various reasons (see figure 1).
At each visit, all current treatments, in particular specific
treatments for AD, are carefully recorded. Nutritional status is
also assessed with the Mini-Nutritional Assessment (MNA)
Changes in the cohort after 1 year of follow-up. * : patient's or
(19). Lastly, caregiver burden is measured with the Zarit
caregiver's medical problem, removal…
Burden Interview (20).
During follow-up, all events occurring between two visits, in
Patients recruited
- Deceased n = 25
particular admissions to hospital or to institutions, use of new
- Institutionalized (follow-up impossible)
support or home assistance services, changes among the
- Lost to follow-up n = 38
patient's family and friends, are carefully recorded together
- Withdrawal of consent n = 34
with deaths, entry to an institution where follow-up is not
possible, and other reasons for premature discontinuation suchas withdrawal of consent, medical problems of patient or
Discontinous follow-up n = 49
caregiver, or loss to follow-up.
Patients who completed the
1st year of follow-up n = 498
Statistical analysis of the data was carried out with SAS 8.0
software. Bivariate analysis was used to describe the changes atone year in cognitive and non-cognitive parameters in the
Overall, of the 693 patients initially recruited, 498 were
patients of the cohort. Wilcoxon's non-parametric test was used
evaluated at 1 year and 49 missed the visit. Table 1 compares
for quantitative variables and the McNemar test for qualitative
the characteristics at inclusion of patients who prematurely
discontinued follow-up (excluding the 25 patients who died)
For the MMS : deterioration is a loss of 3 points or more in
and of those who were still in the study at 1 year (n = 547).
12 months; improvement is an increase of 3 points or more in
Subjects who discontinued follow-up during the first year had a
12 months and stable concern patients whose score at 1 year
significantly lower mean MMS score than the patients who
and score at inclusion differed by between –3 and 3, exclusive.
completed the year (p=0.0064). Their ability to carry out the
For the ADL: deterioration is a loss of 0.5 points or more in 12
activities of daily living was also less (ADL, p=0.0001, IADL
months and improvement is a gain of 0.5 points or more in 12
p<0.0001). Overall, these subjects were at a more advanced
months. For the IADL: deterioration is a loss of 1 point or more
stage of the disease, as shown by the mean CDR-SB score
in 12 months and improvement is gain of 1 point or more in 12
which was significantly higher in subjects who left the study
months. For the NPI: deterioration is an increase of 1 point or
than in those who continued (p=0.0002). These patients were
more in total score in 12 months and improvement is a decrease
also significantly older (p=0.0017). Lastly, absence of specific
of 1 point or more in total score in 12 months. For the measure
AD treatment at inclusion significantly increased the risk of
of weight: deterioration is a loss of 4 % or more of baseline
premature discontinuation during the first year of the study
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
RECENT DATA ON THE NATURAL HISTORY OF ALZHEIMER'S DISEASE
(OR=0.37, p=0.0002 and 95% CI = 0.22-0.64).
ADAS-cog were significantly higher than those obtained atinclusion, with an increase of 2.40 ± 6.10 points (p<0.0001)
Comparison of characteristics at inclusion between patients
Change in ability to carry out the activities of daily living:
followed for 1 year and patients who prematurely discontinued
mean scores on the ADL and IADL measured at the end of 1
follow-up (excluding those deceased, n = 25).
year were significantly lower (p<0.0001) than at inclusion,reflecting greater difficulty in carrying out the basic and
Parameters at
Discontinuation of follow-up
p student
instrumental activities of daily living (table 2). Figure 2 shows
the items most affected by this gradual loss of function.
Concerning the ADL, there was indeed an overall loss for the
mean ± SD
mean ± SD
basic activities of daily living (figure 2 A). For the morecomplex activities (IADL), we observed an increase in the
percentages of dependent subjects after 1 year, whatever the
item considered (figures 2 B). Deterioration was observed in
43.8% of patients on the ADL scale and in 59.1% on the IADL
Age at onset (yr)
Age at diagnosis (yr)
Changes in autonomy in patients followed for 1 year (n = 498)
Age of patient (yr)
for each of the items evaluated by the scales for ADL (2A) and
IADL (2B). ■ = inclusion; ❑ = 1 year
The results presented below concern the 498 subjects who
completed the first year of follow-up.
Cognitive and non-cognitive aspects of AD
Table 2 shows changes in the cognitive and non-cognitive
*** : p<0.0001
parameters during the first year of follow-up.
Change in behavioural disturbances: the mean NPI score
after 1 year was significantly higher than at inclusion, with an
Changes in cognitive parameters, autonomy, behavioural
increase of 1.85 ± 14.83 (p=0.0047). Behavioural disturbances
disturbances, nutritional status and caregiver burden in patients
thus significantly worsened in the cohort as a whole, but we did
followed for 1 year (n = 498).
not observe a significant increase in the mean number ofproblems (table 2). The various problems assessed by the NPI
Mean score at
Mean score
p Wilcoxon
did not all progress in the same way. In fact, for certain
problems the number of patients affected decreased
significantly during the year: this was the case for depression
(p=0.0186) and anxiety (p=0.0048). On the other hand, apathy
(p=0.0196), aberrant motor activity (p<0.0001) and sleep
disturbances (p=0.0495) were present in a significantly greater
NPI (freq x grav) 14.45 ± 14.52
number of patients after 1 year of follow-up (figure 3). Overall
worsening of behavioural disturbances (a score increase of 1
point or more) concerned 51.4% of patients, while 38.3%
improved (table 3).
Cognitive change: the difference between the mean MMS
scores after 1 year and those obtained at inclusion revealed asignificant loss of 1.93 ± 3.74 points (p<0.0001). In addition,36.6% of patients showed a clinically significant loss of 3points or more at the end of the year compared with their MMSscore at inclusion (table 3). Similarly, scores at 1 year on the
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
THE JOURNAL OF NUTRITION, HEALTH & AGING
(respectively 100% and 75%), about 70% of patients who had a
Stability, improvement and deterioration of cognitive
score of 4 or 5 at inclusion remained stable or improved and
parameters, autonomy, behavioural disturbances, nutritional
lastly, 5% of patients with a GDS score of 6 at the first visit had
status and caregiver burden in patients followed for 1 year
become worse. In addition, the mean CDR-SB score at the end
of the year was significantly higher than at inclusion(p<0.0001) (table 2).
Changes in behavioural disturbances measured by the NPI in
patients followed for 1 year (n = 498). * : p<0.05, ** : p<0.02,
*** : p<0.01. ■ = inclusion; ❑ = 1 year
NPI (freq x grav)
Global change: Figure 4 shows the distribution of patients in
the CDR and GDS scales at inclusion and at 1 year. Inaccordance with the inclusion criteria, the majority of patients(77%) had CDR scores of 0.5 or 1 and 62% had scores of 2, 3or 4 on Reisberg's GDS, indicating mild to moderate AD. At 1
year, the proportions had changed: a larger number of patients(53%) had a score of 5, 6 or 7 on Reisberg's scale and 37% hada CDR score of 2 or 3. Table 4 shows the outcome at 1 year ofthe patients according to their CDR or Reisberg's GDS status atinclusion. For the CDR, half of the patients who had a score of0.5 at inclusion showed no change, over 60% of patients whohad a score of 1 or 2 at the first visit remained stable or evenimproved, and 40% of patients with a score of 3 at inclusionhad also improved at 1 year. For Reisberg's GDS, subjects withscores of 2 or 3 at inclusion declined during the year
Change in nutritional status: mean weight was stable after 1
Outcome of patients followed up for 1 year according to their CDR (4A) and GDS (4B) status at inclusion.
CDR score at inclusion
Outcome at 1 year % (n)
GDS score at inclusion
Outcome at 1 year % (n)
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
RECENT DATA ON THE NATURAL HISTORY OF ALZHEIMER'S DISEASE
year of follow-up compared with its value at inclusion (table 2).
Even if the MNA score decreased not significantly (p=0.0531),
Changes in living arrangements of patients followed for 1 year
the loss was close to the threshold of significativity. About 20%
(n = 498). ■ = inclusion; ❑ = 1 year
of patients presented a clinically significant weight loss (≥ 4%)during this first year of follow-up and in 20.2% the MNA scoredecreased (table 3).
Changes in the distribution of patients followed up for 1 year (n
= 498) on the CDR (4A) and Reisberg's scales (4B).
■ = inclusion; ❑ = 1 year
Treatments: At inclusion, 80.8% of patients were already
receiving specific treatment for AD. Among them, 28.7% hadbeen treated for 1 year or more, 28.9% for 3 to 12 months and23.2% had been treated for less than 3 months. In addition,10.5% of patients started specific AD treatment during theinclusion visit. Of the patients who completed the 1-yearfollow-up, 91.3% were being treated at the beginning of thestudy. At 1 year, 86.8% of patients were treated and had beenfor the entire year, while only 3.2% had never been treated and10% had been treated for less than 12 months. The majority ofpatients in this cohort who were treated throughout the yearwere receiving AChEIs and very few were taking Ebixa.
Use of support services: At inclusion as at 1 year, patients
mainly used home help services and the proportion of patientsreceiving such assistance did not change significantly (42.7% atinclusion then 45.5%, p=0.1229), nor did use of day hospitals(2.2% then 1.9%, p=0.7389), visits to the doctor (60.5% then
Medical and social characteristics
57.9%, p=0.2273), surveillance during the day or at night (4%
Living arrangements: At inclusion, 28% of patients lived
and 4%, p=0.4386) or use of a portable alarm (4.4% then 4.6%,
alone at home and at 1 year this percentage was about 26%.
p=0.7963). On the other hand, after 1 year of follow-up, we
Both at inclusion and at the end of the year of follow-up, the
observed that significantly more patients used day care centers
majority of patients lived with a caregiver at home: 69.4% and
(1.7% at inclusion and 5.2% at 1 year, p=0.0010), nursing visits
then 68%. The caregiver was generally the spouse: 60.3% at
at home (16.1% then 24.1%, p<0.0001), physiotherapists (6.6%
inclusion and 58.1% at 1 year, rather than another family
then 10.1%, p=0.0071), speech therapists (8.9% then 11.9%,
member: 8.7% at inclusion and 9.5% at 1 year, while at each
p=0.0423) and meal delivery services (5.9% then 9.6%,
timepoint 0.4% had a formal caregiver. At 1 year, about 5%
p=0.0053) (figure 6).
(n=25) of subjects had entered an institution but the majority
Caregiver burden: Comparing the scores obtained on the
still lived at home (figure 5).
Zarit scale completed by the same caregivers at inclusion and at
Hospitalisation: About 25% of patients had been admitted to
12 months (table 2), no significant difference was found. The
hospital at least once during the year. These admissions were
Zarit score remained stable or improved for 84.7% of
repeated in 26 subjects (5.7%): 15 patients (3.3%) were
caregivers (table 3) and the mean remained greater than 20,
hospitalised twice, 10 (2.2%) 3 times and 1 (0.2%) 5 times.
corresponding to mild or moderate burden.
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
THE JOURNAL OF NUTRITION, HEALTH & AGING
depression were present in fewer patients at 1 year than at
Changes in use of support services by patients followed for 1
inclusion. This improvement was observed in 38.3% of
year (n = 498). ■ = inclusion; ❑ = 1 year *** : p < 0.0001,
patients. For behavioural disturbances also, there seemed to be
** : p < 0.01, * p < 0.05.
a slowing of the progression of AD, as the mean NPI scoreincreased by 1.85 ± 14.83 points during the year, whereas otherauthors observed an increase of 3.9 points in 6 months inpatients with mild or moderate AD receiving placebo (24). Inaddition, the mean number of problems presented by thepatients remained stable over the year, with no onset of newproblems in the cohort.
Within the cohort, there was a large proportion of patients
receiving treatment, mainly AChEIs as they were still at mild tomoderate stages of AD. The large number of treated patientscould partly explain the differences in progression observed. Infact, 86.8% of patients received specific AD treatmentthroughout the year of follow-up, and the impact of thesetreatments, which in clinical trials have been shown to slow thedecline of cognitive function, was partly confirmed in ourresults (5,25,7,26). However, it is impossible to dissociate theeffect of these medications from that of non-pharmacological
management of the patient, which has progressed over recent
years thanks to better knowledge of the troubles related to AD.
Concerning nutritional status, after 1 year, the mean MNA
score decrease was close to the threshold of significativity
Discussion
(p=0.0531) showing that there was a tendency of worseningwith 20.2% of subjects who reported a deterioration. But the
As expected, our evaluations of the cognitive aspects of the
mean score even remained above 23.5 indicating that the cohort
disease demonstrated changes in the status of the patients. The
maintained as a whole a good nutritional status. The mean
significantly decreased MMS scores and increased ADAS-cog
weight did not differ significantly from its value at inclusion
scores at the end of the first year of follow-up reflected
even if 91.3% of patients who completed 1 year of follow-up
alteration of cognitive functions. However, this deterioration
were treated with AChEIs after the inclusion visit, which have
seems relative if we compare our results with those of the
been found capable of inducing weight loss in the course of
literature. For the MMS, we observed a decrease of 1.94 ± 3.74
clinical trials (5,27,28). Weight loss is also a characteristic of
points over the year, whereas it was 3.6 ± 4.4 points in the
AD (29). In most clinical studies of AChEIs, the dose
CERAD study (21) of patients not treated for AD recruited
escalation phase for each treatment was short, which could
between 1987 and 1988 and who had a slightly more advanced
explain the frequency and importance of side effects observed,
stage of disease at inclusion (MMS: 18.7 ± 4.5) (21). In our
weight loss in particular (5,27,28) but in other studies in which
study, only 36.6% of patients lost 3 points or more on the
the maximum dosage was reached over a longer period there
MMS. ADAS-cog scores also differed from baseline results, as
were few or no side effects (3,6). In our study, after 1 year of
the mean score increased by 2.4 ± 6.1 points during the year
follow-up we did not observe any change in the mean weight of
whereas in non-treated patients it increased by approximately 5
the cohort. It is probable that the prescription and initiation of
points over the same time period (22). In parallel, the loss of
AChEI treatment by the practitioners took place over a longer
certain abilities measured by the ADL and IADL scales also
period than in the clinical trials. But this result may also be a
indicated a worsening of the disease. But in this case as well,
consequence of the fact that at inclusion the majority of patients
the decline in autonomy seemed less pronounced: in our
had already been receiving treatment. In fact, 80.8% of them
REAL.FR study, decrease in the IADL was – 1.00 ± 1.46,
were already treated and the side effects may have already been
whereas other authors found a decrease of – 2.06 ± 3.27 in
controlled when the final dosage was reached. In addition, time
patients who were not treated for AD (23). Overall, the change
elapsing since treatment was started had no effect on the risk of
of the CDR-SB score and the distribution of patients in the
weight loss. Patients who started treatment at the initial visit did
Reisberg and CDR scales also reflected deterioration of the
not have a significantly greater risk of weight loss than the
general condition within the cohort. The NPI scores also
others, in spite of effective dosages being reached during the
demonstrated a worsening of behavioural disturbances, with an
follow-up period.
increasing number of patients presenting apathy, aberrant motor
Although the status of the patients deteriorated, we have
activity and sleep disturbances. In parallel, anxiety and
shown that caregiver burden as measured by the Zarit scale did
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
RECENT DATA ON THE NATURAL HISTORY OF ALZHEIMER'S DISEASE
not significantly vary during the first year of follow-up. It
increased for only 15.3% of caregivers, which did not thereforereflect the worsening of the disease as measured by the various
Grant: this work was supported by a grant from the Clinical Research Hospital
Program from the French Ministry of Health (PHRC N° 98-47N, PHRC N° 0101001).
tests and the impact that this could have on caregivers. Theburden related to the task of caregiving is experienceddifferently according to the progression of the patient's disease
The REAL.FR group: Principal investigator: Prof. B. Vellas
and depends subjectively on the personal emotional feelings of
(Toulouse); Associate investigators: Prof. M. Rainfray,
the caregiver (30). The impact of treatments, pharmacological
Dr S. Richard-Harston (Bordeaux); Prof. A. Franco, Dr P. Couturier
or otherwise, on the progression of AD may explain the
(Grenoble); Prof. F. Pasquier, Dr M. Mackowiak, V. Sorel (Lille);
stability of the Zarit scores as the worsening of the disease had
Dr B. Frigard, Dr H. Idiri, DR Dr K. Gallouj (Lille); Dr B. Michel,L. Margulies (Marseille); Prof. Cl. Jeandel (Montpellier);
been slowed, with maintenance of function making the
Prof. J. Touchon, Dr F. Portet, Dr S. Lerouge (Montpellier);
caregiver's task easier. Various studies have demonstrated that
PrProf. Ph. Robert, Dr P. Brocker, C. Bertogliati (Nice);
the main cause of increased caregiver burden is increased levels
Prof. B. Forette, Dr L. Teillet, Dr L. Lechowski (Paris);
of behavioural disturbance (31,32). According to our results,
Prof. J. Belmin, Dr. S. Pariel-Madjelssi (Paris); Prof. M. Verny,
the behavioural disturbances of the patients in our cohort
Dr MA. Artaz (Paris); Prof. F. Forette, Dr AS. Rigaud, Dr F. Latour
worsened only very slightly (+ 1.85 ± 14.83 points) and there
(Paris); Prof. P. Jouanny, Dr S. Belliard, Dr O. Michel (Rennes);
was even an improvement in 38.3% of subjects. This could
Dr C. Girtanner, Dr Thomas-Anterion (Saint Etienne); Study
explain the stability of the Zarit scores. It is also possible that
coordinators: F. Cortes, Dr S. Gillette-Guyonnet,
the standardized, regular patient follow-up as part of the
Prof. F. Nourhashemi, Dr P.J. Ousset (Toulouse); Epidemiologist:Dr S. Andrieu; Data processing: C. Cantet (Toulouse)
REAL.FR study, with 6-monthly visits and evaluations, had aninfluence on the burden experienced by the caregiver, who feltmore supported in facing the difficulties engendered by the
progression of their relative's disease.
At the end of the first year of follow-up, 94% of subjects
Mohs RC, Schmeidler J, Aryan M. Longitudinal studies of cognitive, functional and
were still living at home with their spouse, a family member or
behavioural change in patients with Alzheimer's disease. Stat Med 2000;19:1401-
alone, in spite of worsening of the disorder and an increased
Cummings JL, Kaufer D. Neuropsychiatric aspects of Alzheimer's disease: the
number of entries into an institution. The high proportion of
cholinergic hypothesis revisited. Neurology 1996;47:876-883.
patients still living at home may be explained by the slightly
Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, et al.; "312"Study Group. A 1-year, placebo-controlled preservation of function survival study of
greater use made of the various support services, although this
donepezil in AD patients. Neurology 2001;57:481-488.
concerned only a limited number of patients (about 10%,
Rogers SL, Doody RS, Pratt RD, Ieni JR. Long-term efficacy and safety of donepezilin the treatment of Alzheimer's disease: final analysis of a US multicenter open-label
excluding nursing visits at home), and by slowing of the
study. Eur Neuropsychopharmacol 2000;10:195-203.
progression of AD and stability of caregiver burden, whose
Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, et al., on
increase generally leads to institutionalization (33).
behalf of the B303 Exelon Study Group. Efficacy and safety of rivastigmine inpatients with Alzheimer's disease: international randomised controlled trial. BMJ
Lastly, for patients who prematurely discontinued follow-up
1999;318:633-640.
in the course of the year, we observed that they were at a more
Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A 5-month,randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-
advanced stage of the disease at inclusion. In addition, there
10 Study Group. Neurology 2000;54:2269-2276.
were significantly fewer premature withdrawals among the
Wilcock GK, Lilienfeld S, Gaens E, on behalf of the Galantamine International-1Study Group. Efficacy and safety of galantamine in patients with mild to moderate
treated patients, which could reflect a protective effect of
Alzheimer's disease: multicenter randomised controlled trial. BMJ 2000;321:1445-
Our findings demonstrate a slowing of the progression of
Winblad B, Poritis N. Memantine in severe dementia: results of the 9M-Best Study(Benefit and efficacy in severely demented patients during treatment with
AD as compared with the data of the literature. This
memantine). Int J Geriatr Psychiatry 1999;14:135-146.
observation may be explained by advances in patient
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinicaldiagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under
management and by the impact of specific AD medication,
the auspices of Department of Health and Human Services Task Force on
which was received by the great majority of subjects in our
Alzheimer's Disease. Neurology 1984;34:939-944.
10. American Psychiatric Association. Diagnostic and Statistical Manual of Mental
cohort. This change in disease progression influenced caregiver
Disorders, 4th ed. Washington DC: APA, 1994.
burden and made it possible to keep patients in their own home.
11. Gillette-Guyonnet S, Nourhashemi F, Andrieu S, Cantet C, Micas M, Ousset PJ, et
It would thus seem that the impact of present treatment and
al.; REAL.FR group. The REAL.FR research program on Alzheimer's disease and itsmanagement: methods and preliminary results. J Nutr Health Aging 2003;7:91-96.
management on the natural history of AD is important not only
12. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for
to maintain the general status of the patient but also for the
grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
family and relatives. These results thus justify diagnosis and
13. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J
appropriate management of dementias of Alzheimer type,
14. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. The index of ADL: A
allowing stabilization or improvement of the condition in
standardized measure of biological and psychosocial function. JAMA 1963;185:914-
63.4% of patients at 1 year, while 36.6% showed clinically
significant deterioration in spite of overall and pharmacological
15. Lawton MP, Brody EM. Assessment of older people: self-maintaining and
instrumental activities of daily living. Gerontologist 1969;9:179-186.
The Journal of Nutrition, Health & AgingVolume 9, Number 2, 2005
THE JOURNAL OF NUTRITION, HEALTH & AGING
16. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J.
24 week, double-blind, placebo-controlled trial of donepezil in patients with
The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in
Alzheimer's disease. Neurology 1998;50:136-145.
dementia. Neurology 1994;44:2308-2314.
26. Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm
17. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for
A-L, Zhang R, Haglund A, Subbiah P and the Donepezil Nordic Study Group. A 1-
the staging of dementia. Br J Psychiatry 1982;140:566-572.
year, randomised, placebo-controlled study of donepezil in patients with mild to
18. Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for
moderate AD. Neurology 2001;57:489-495.
assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136-1139.
27. Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: A 6-month
19. Vellas B, Guigoz Y, Garry PJ, Nourhashemi F, Bennahum D, Lauque S, et al. The
randomized, placebo-controlled trial with a 6-month extension. The Galantamine
Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of
USA-1 Study Group. Neurology 2000;54:2261-2268.
elderly patients. Nutrition 1999;2:116-122.
28. Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, et al. A
20. Zarit SH, Reever K, Bach-Peterson J. Relatives of the impaired elderly: Correlates of
randomized, double-blind, placebo-controlled study of the efficacy and safety of
feelings of burden. Gerontologist 1980;20:649-655.
donepezil in patients with Alzheimer's disease in the nursing home setting. J Am
21. Morris JC, Edland S, Clark C, Galasko D, Koss E, Mohs R, et al. The Consortium to
Geriatr Soc 2001;49:1590-1599.
Establish a Registry for Alzheimer's Disease (CERAD). Part IV. Rates of cognitive
29. White H, Pieper C, Schmader K, Fillenbaum G. Weight change in Alzheimer's
change in the longitudinal assessment of probable Alzheimer's disease. Neurology
disease. J Am Geriatr Soc 1996;44:265-272.
Whalen S, Finucane TE. Predictors of nursing home placement in
22. Stern RG, Mohs RC, Davidson M, Schmeidler J, Silverman J, Kramer-Ginsberg E, et
community-based long-term care. J Am Geriatr Soc 1995;4:761-766.
al. A longitudinal study of Alzheimer's disease: measurement, rate and predictors of
31. Coen RF, Swanwick GR, O'Boyle CA, Coakley C. Behaviour disturbance and other
cognitive deterioration. Am J Psychiatry 1994;151:390-396.
predictors of carer burden in Alzheimer's disease. Int J Geriatr Psychiatry
23. Green CR, Mohs RC, Schmeidler J, Aryan M, Davis KL. Functional decline in
Alzheimer's disease: a longitudinal study. J Am Geriatr Soc 1993;41:654-661.
32. Donaldson C, Tarrier N, Burns A. Determinants of carer stress in Alzheimer's
24. Morris JC, Cyrus PA, Orazem J, Mas J, Bieber F, Ruzicka BB, et al. Metrifonate
disease. Int J Geriatr Psychiatry 1998;13:248-256.
benefits cognitive, behavioral and global function in patients with Alzheimer's
33. Cohen CA, Gold DP, Shulman KI, Wortley JT, McDonald G, Wargon M. Factors
disease. Neurology 1998;50:1222-1230.
determining the decision to institutionalize dementing individuals: a prospective
25. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff L; Donepezil Study Group. A
study. Gerontologist 1993;33:714-720.
Source: http://www.mna-elderly.com/publications/194.pdf
praktikum Versuch Nummer F-09/10: Isolierung von Ribosomen und Bestimmung ribosoma- Sven Enterlein 108 097 236 174 Versuch Nummer FF---009 I. Einleitung Die Zentrifugation bildet eine effektive Möglichkeit, Stoffe nach Größe und Gestalt zu trennen. Die Trennung kann entweder einfach zwischen einer festen und einer flüssigen Phase erfolgen, aber auch unterschiedlich große Partikel können (aus einer Lösung) ge-trennt werden. Physikalische Einflüsse dabei sind Reibung, Auftrieb, Viskosität, Dichte und Zentrifugalkraft. Die treibende Kraft ist die letztgenannte Zentrifugalkraft; sie steht senkrecht zur Drehachse und ist nach außen gerichtet. Durch sie erfahren die Teilchen eine Beschleunigung, die als Zentrifugalbeschleunigung bezeichnet wird. Sie hängt vom Radius r und der Winkelgeschwindigkeit ! ab über
It Can Happen to Anyone… • Anyone can get seasick. It won't kill you, but for a while you may wish it would. • If you've had motion sickness before, plan ahead and take an OTC drug before embarking. Or get a prescription for The English words "nautical" and "nausea" derive brain incorrectly interprets the distress caused by scopolamine or another powerful antiemetic (antinausea) drug.