Bahlmann, Miriam

Bartenstein, P.

Preuss, Ulrich W.

Schütz, Christian G.

Soyka, Michael

English

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Short Reports 57Eur Neurol 2001;45:57–58Memantine Treatment in Alcohol Dementia:Rapid PET Changes and Clinical CourseU.W. Preuss a, M. Bahlmann a, P. Bartenstein b, C.G. Schütz a,M. Soyka aaPsychiatrische Klinik und Poliklinik, Ludwig-Maximilians-Universität München und b Klinik und Poliklinik fürStrahlentherapie und Radiologische Onkologie, TechnischeUniversität München, DeutschlandAlcohol dementia (ALD) usually follows long-term alcohol de-pendence. The major psychiatric features of ALD are general loss ofshort- and long-term memory combined with disturbances in con-centration and a decrease in intellectual capacity, all of which persistduring abstinence. Despite its clinical importance, few studies havebeen published up to now on medical treatment of ALD and otheralcohol-induced mental disorders [1]. The central nervous gluta-matergic system, with its N-methyl-D-aspartate (NMDA) receptors,is suggested to be involved in toxic neuronal loss [2] due to anincreased glutamatergic neurotransmission during repeated alcoholwithdrawal and may subsequently contribute to the development ofALD. The low-affinity NMDA receptor antagonist memantine (ada-mantine, 1-amino-3,5-dimethyladamantine hydrochloride, CAS41100-52-1) modulates the glutamatergic system most likely throughCa2+ influx blockage of NMDA receptors [3] and shows positiveeffects on memory in the treatment of other psychogeriatric disorderswith memory loss such as Alzheimer’s dementia (AD) or Parkinson’sdisease [4].We would like to report the case of a 71-year-old female patientwith chronic alcoholism for at least 30 years. She was found neglectedin her home and was admitted to our ward from an emergency unitwith symptoms of disorientation, apraxia, ataxia, severe short- andlong-term memory disturbances, deficits in intellectual capacity andconcentration. There were no signs of electrolyte imbalance onadmission. A further thorough neurological investigation and NMRshowed a general atrophy without severe basal brain damage of Wer-nicke encephalopathy. No other signs of Wernicke encephalopathy,i.e. ophthalmoplegia or evidence of hepatic encephalopathy such asflapping tremor, were found. Ultrasound of brain arteries showedsome plaques without hemodynamic compromise. After excludingAlzheimer’s disease or vascular dementia, the diagnosis of ALDaccording to ICD10 criteria was made.58 Short ReportsFig. 1. FDG-PET 1 week after admission (study 1) and 5 weeks after starting the memantine treatment (study 2). Theinitial study showed a bilateral, symmetrical decrease in regional cerebral glucose consumption involving the frontal,parietal and temporal lobes. The second study, performed 5 weeks later, revealed a nearly normal pattern of glucosemetabolism.We started treatment with memantine for 5 weeks with a dosageup to a maximum of 30 mg/day to improve memory and intellectualcapacity. The patient was neuropsychologically tested before andretested after 5 weeks of treatment employing the same psychologicaltests. Improvement was seen in MMSE (Mini-Mental State Exami-nation) [5] from 18 to 22 points, and CERAD Verbal Fluency (Con-sortium to Establish a Registry for Alzheimer’s Disease) [6] from 10to 12 points. CERAD Wordlist Recall improved from 0 to 5 andCERAD Drawing from 6 to 8.Parallel to psychological testing, an 18F-fluorodeoxyglucose-posi-tron emission tomography (FDG-PET) was performed 1 week afteradmission and 5 weeks after starting the memantine treatment, asextensively described elsewhere [7]. The initial study revealed a bilat-eral, symmetrical decrease in regional cerebral glucose consumptioninvolving the frontal lobes and extended areas of the parietal andtemporal lobes. The second study, performed 5 weeks later, revealeda nearly normal pattern of glucose metabolism (fig. 1). However,despite these findings and improvement of some intellectual andmemory functions, severe memory deficits and disorientation per-sisted. The patient was recommended for continued inpatient carebut no deterioration of the mental abilities was observed even 1 yearafter discharge.This is the first report on memantine treatment in an ALDpatient. To our knowledge, this is also the first report on FDG-PETin an ALD patient. Significant changes in cerebral blood flow after5 weeks of memantine treatment were revealed using FDG-PET,which were paralleled by moderate improvements in neuropsycho-logical testing. It supports the hypothesis that low-affinity NMDAantagonists have a neuroprotective effect even in manifest ALDpatients [3, 4].The PET findings prior to the memantine treatment were verysimilar to those in patients with AD. Both AD and ALD can be diag-nosed after excluding other kinds of dementia and their FDG-PETfindings may be similar. In our case, a 33-year history of severe alco-hol intake was reported. The clinical course in AD is deterioratingover time whereas the mental abilities in this case remained stableunder abstinent conditions and even improved slightly. This is veryuntypical for ALD. Furthermore, a well-known phenomenon is aspontaneous improvement in mental abilities in patients sufferingfrom Korsakoff’s syndrome or ALD [8]. This could not be proven inthis case report. Thus, larger, controlled double-blind trials with thisagent in ALD patients are needed to evaluate the use of memantinein alcohol-induced dementia syndromes.References1 Preuss UW, Soyka M: Wernicke-Korsakow syndrome: Clinical aspects,pathophysiology and therapeutic approaches. Fortschr Neurol Psychiatr1997;65:413–420.2 Tsai GC, Gastfried DR, Coyle JT: The glutamertergic basis of human alco-holism. Am J Psychiatry 1995;152:332–340.3 Kornhuber J, Weller M: Psychotogenicity and N-methyl-D-aspartate recep-tor antagonism: Implications for neuroprotective pharmacotherapy. BiolPsychiatry 1997;41:135–144.4 Muller WE, Mutschler E, Riederer P: Noncompetitive NMDA receptorantagonists with fast open-channel blocking kinetics and strong voltagedependency as potential therapeutic agents for Alzheimer’s dementia.Pharmacopsychiatry 1995;28:113–124.5 Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’. A practicalmethod for grading the cognitive state of patients for the clinician. J Psy-chiatr Res 1975;12:189–198.6 Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G,Mellits ED, Clark C: The Consortium to Establish a Registry for Alzhei-mer’s Disease (CERAD). I. Clinial and neuropsychological assessment ofAlzheimer’s disease. Neurology 1989;39:1159–1165.7 Bartenstein P, Minoshima S, Hirsch C, Buch K, Willoch F, Mosch D,Schad D, Schwaiger M, Kurz A: Quantitative assessment of cerebral bloodflow in patients with Alzheimer’s disease by SPECT. J Nucl Med 1997;38:1095–1101.8 Khudik VA: Dynamics of intellectual mnestic disorders in alcoholism (inRussian). Zh Nevropatol Psikhiatr Im S S Korsakova 1983;83:110–115.U.W. Preuss, MDPsychiatrische Klinik und PoliklinikLudwig-Maximilians-Universität MünchenNussbaumstrasse 7, D–80336 München (Germany)Tel. +49 89 5160 5740, Fax +49 89 5160 5748/4749E-Mail up@psy.med.uni-muenchen.de

A practical method for grading the cognitive state of patients for the clinician.

A: Quantitative assessment of cerebral blood flow in patients with Alzheimer’s disease by SPECT.

C: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). I. Clinial and neuropsychological assessment of Alzheimer’s disease.

Coyle JT: The glutamertergic basis of human alcoholism.

Dynamics of intellectual mnestic disorders in alcoholism (in Russian). Zh Nevropatol Psikhiatr Im

Noncompetitive NMDA receptor antagonists with fast open-channel blocking kinetics and strong voltage dependency as potential therapeutic agents for Alzheimer’s dementia. Pharmacopsychiatry

Psychotogenicity and N-methyl-D-aspartate receptor antagonism: Implications for neuroprotective pharmacotherapy. Biol Psychiatry

Wernicke-Korsakow syndrome: Clinical aspects, pathophysiology and therapeutic approaches. Fortschr Neurol Psychiatr

Memantine treatment in alcohol dementia: Rapid PET changes and clinical course

Universität München: Elektronischen Publikationen

Short Reports 57
Eur Neurol 2001;45:57–58
Memantine Treatment in Alcohol Dementia:
Rapid PET Changes and Clinical Course
U.W. Preuss a, M. Bahlmann a, P. Bartenstein b, C.G. Schütz a,
M. Soyka a
aPsychiatrische Klinik und Poliklinik, Ludwig-Maximilians-
Universität München und b Klinik und Poliklinik für
Strahlentherapie und Radiologische Onkologie, Technische
Universität München, Deutschland
Alcohol dementia (ALD) usually follows long-term alcohol de-
pendence. The major psychiatric features of ALD are general loss of
short- and long-term memory combined with disturbances in con-
centration and a decrease in intellectual capacity, all of which persist
during abstinence. Despite its clinical importance, few studies have
been published up to now on medical treatment of ALD and other
alcohol-induced mental disorders [1]. The central nervous gluta-
matergic system, with its N-methyl-D-aspartate (NMDA) receptors,
is suggested to be involved in toxic neuronal loss [2] due to an
increased glutamatergic neurotransmission during repeated alcohol
withdrawal and may subsequently contribute to the development of
ALD. The low-affinity NMDA receptor antagonist memantine (ada-
mantine, 1-amino-3,5-dimethyladamantine hydrochloride, CAS
41100-52-1) modulates the glutamatergic system most likely through
Ca2+ influx blockage of NMDA receptors [3] and shows positive
effects on memory in the treatment of other psychogeriatric disorders
with memory loss such as Alzheimer’s dementia (AD) or Parkinson’s
disease [4].
We would like to report the case of a 71-year-old female patient
with chronic alcoholism for at least 30 years. She was found neglected
in her home and was admitted to our ward from an emergency unit
with symptoms of disorientation, apraxia, ataxia, severe short- and
long-term memory disturbances, deficits in intellectual capacity and
concentration. There were no signs of electrolyte imbalance on
admission. A further thorough neurological investigation and NMR
showed a general atrophy without severe basal brain damage of Wer-
nicke encephalopathy. No other signs of Wernicke encephalopathy,
i.e. ophthalmoplegia or evidence of hepatic encephalopathy such as
flapping tremor, were found. Ultrasound of brain arteries showed
some plaques without hemodynamic compromise. After excluding
Alzheimer’s disease or vascular dementia, the diagnosis of ALD
according to ICD10 criteria was made.
58 Short Reports
Fig. 1. FDG-PET 1 week after admission (study 1) and 5 weeks after starting the memantine treatment (study 2). The
initial study showed a bilateral, symmetrical decrease in regional cerebral glucose consumption involving the frontal,
parietal and temporal lobes. The second study, performed 5 weeks later, revealed a nearly normal pattern of glucose
metabolism.
We started treatment with memantine for 5 weeks with a dosage
up to a maximum of 30 mg/day to improve memory and intellectual
capacity. The patient was neuropsychologically tested before and
retested after 5 weeks of treatment employing the same psychological
tests. Improvement was seen in MMSE (Mini-Mental State Exami-
nation) [5] from 18 to 22 points, and CERAD Verbal Fluency (Con-
sortium to Establish a Registry for Alzheimer’s Disease) [6] from 10
to 12 points. CERAD Wordlist Recall improved from 0 to 5 and
CERAD Drawing from 6 to 8.
Parallel to psychological testing, an 18F-fluorodeoxyglucose-posi-
tron emission tomography (FDG-PET) was performed 1 week after
admission and 5 weeks after starting the memantine treatment, as
extensively described elsewhere [7]. The initial study revealed a bilat-
eral, symmetrical decrease in regional cerebral glucose consumption
involving the frontal lobes and extended areas of the parietal and
temporal lobes. The second study, performed 5 weeks later, revealed
a nearly normal pattern of glucose metabolism (fig. 1). However,
despite these findings and improvement of some intellectual and
memory functions, severe memory deficits and disorientation per-
sisted. The patient was recommended for continued inpatient care
but no deterioration of the mental abilities was observed even 1 year
after discharge.
This is the first report on memantine treatment in an ALD
patient. To our knowledge, this is also the first report on FDG-PET
in an ALD patient. Significant changes in cerebral blood flow after
5 weeks of memantine treatment were revealed using FDG-PET,
which were paralleled by moderate improvements in neuropsycho-
logical testing. It supports the hypothesis that low-affinity NMDA
antagonists have a neuroprotective effect even in manifest ALD
patients [3, 4].
The PET findings prior to the memantine treatment were very
similar to those in patients with AD. Both AD and ALD can be diag-
nosed after excluding other kinds of dementia and their FDG-PET
findings may be similar. In our case, a 33-year history of severe alco-
hol intake was reported. The clinical course in AD is deteriorating
over time whereas the mental abilities in this case remained stable
under abstinent conditions and even improved slightly. This is very
untypical for ALD. Furthermore, a well-known phenomenon is a
spontaneous improvement in mental abilities in patients suffering
from Korsakoff’s syndrome or ALD [8]. This could not be proven in
this case report. Thus, larger, controlled double-blind trials with this
agent in ALD patients are needed to evaluate the use of memantine
in alcohol-induced dementia syndromes.
References
1 Preuss UW, Soyka M: Wernicke-Korsakow syndrome: Clinical aspects,
pathophysiology and therapeutic approaches. Fortschr Neurol Psychiatr
1997;65:413–420.
2 Tsai GC, Gastfried DR, Coyle JT: The glutamertergic basis of human alco-
holism. Am J Psychiatry 1995;152:332–340.
3 Kornhuber J, Weller M: Psychotogenicity and N-methyl-D-aspartate recep-
tor antagonism: Implications for neuroprotective pharmacotherapy. Biol
Psychiatry 1997;41:135–144.
4 Muller WE, Mutschler E, Riederer P: Noncompetitive NMDA receptor
antagonists with fast open-channel blocking kinetics and strong voltage
dependency as potential therapeutic agents for Alzheimer’s dementia.
Pharmacopsychiatry 1995;28:113–124.
5 Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’. A practical
method for grading the cognitive state of patients for the clinician. J Psy-
chiatr Res 1975;12:189–198.
6 Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G,
Mellits ED, Clark C: The Consortium to Establish a Registry for Alzhei-
mer’s Disease (CERAD). I. Clinial and neuropsychological assessment of
Alzheimer’s disease. Neurology 1989;39:1159–1165.
7 Bartenstein P, Minoshima S, Hirsch C, Buch K, Willoch F, Mosch D,
Schad D, Schwaiger M, Kurz A: Quantitative assessment of cerebral blood
flow in patients with Alzheimer’s disease by SPECT. J Nucl Med 1997;38:
1095–1101.
8 Khudik VA: Dynamics of intellectual mnestic disorders in alcoholism (in
Russian). Zh Nevropatol Psikhiatr Im S S Korsakova 1983;83:110–115.
U.W. Preuss, MD
Psychiatrische Klinik und Poliklinik
Ludwig-Maximilians-Universität München
Nussbaumstrasse 7, D–80336 München (Germany)
Tel. +49 89 5160 5740, Fax +49 89 5160 5748/4749
E-Mail up@psy.med.uni-muenchen.de


U.W. Preuss

M. Bahlmann

P. Bartenstein

C.G. Schütz

M. Soyka

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Memantine Treatment in Alcohol Dementia: Rapid PET Changes and Clinical Course

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Memantine treatment in alcohol dementia: Rapid PET changes and clinical course

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