Original Research Article
Accepted: May 27, 2003
Dement Geriatr Cogn Disord 2004;17:21–28
DOI: 10.1159/000074139
Rapidly Progressive Aphasic Dementia
with Motor Neuron Disease:
A Distinctive Clinical Entity
Marco Catani a, b Massimo Piccirilli c Maria Concetta Geloso f
Antonio Cherubini b Giancarlo Finali d Gianpiero Pelliccioli e
Umberto Senin b Patrizia Mecocci b
a Institute of Psychiatry, London, UK; b Institute of Gerontology and Geriatrics and c Unit of Cognitive Rehabilitation,
University of Perugia, d Spinal Cord Unit and e Department of Neuroradiology, AO Perugia, Perugia, and
f Institute of Anatomy, Università Cattolica del Sacro Cuore, Rome, Italy
Key Words
Progressive aphasia W Motor neuron disease W
Frontotemporal dementia
Abstract
The association of motor neuron disease (MND) with
rapidly progressive aphasic dementia has been recog-
nized as a distinct clinical syndrome within the group of
frontotemporal dementias (FTDs). Although the clinical
and neuropsychological features of this syndrome have
been defined, a small number of post-mortem studies
have been published with heterogeneous neuropatho-
logical findings. We performed cognitive, neuro-imaging
and neuropathological studies on a 71-year-old male
with rapidly progressive aphasic dementia and MND. We
initially found a selective non-fluent aphasia associated
with hypoperfusion of the left frontotemporal cortex.
The clinical and instrumental assessment was done at the Institute
of Gerontology and Geriatrics in Perugia, the histological study at
the Institute of Anatomy in Rome, Italy.
© 2004 S. Karger AG, Basel
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Published online: October 13, 2003
Proton magnetic resonance spectroscopy revealed an
asymmetric change of brain metabolites, with greater
changes in the left temporal lobe. The bulbar manifesta-
tions of MND occurred over the following 6 months, and
the patient died of bronchopneumonia. The neuropatho-
logical examination revealed loss of neurons in the
hypoglossal nucleus and anterior horns of the cervical
spinal cord with microvacuolation and dot-like ubiquitin-
positive deposits in the frontoparietotemporal cortex,
but no changes suggestive of Alzheimer’s, Pick’s or Lewy
body disease. These findings support the conclusion that
MND with rapidly progressive aphasic dementia is a dis-
tinctive clinical entity within the group of FTD-MND.
Copyright © 2004 S. Karger AG, Basel
Introduction
In 1993, Caselli et al. [1] reported 7 patients affected by
a rapidly progressive aphasic dementia associated with
bulbar onset motor neuron disease (MND). Based on
these early cases and other case reports [2, 3], the associa-
tion has been proposed to represent a distinctive clinical
Marco Catani, MD
Section of Old Age Psychiatry
Institute of Psychiatry
London SE5 8AF (UK)
Tel. +44 20 7848 0550, Fax +44 20 7848 0632, E-Mail m.catani@iop.kcl.ac.uk
Table 1. Neuropsychological assessment
January 2001 June 2001 December 2001

General cognitive functions

MMSE (30) 29 24 18
Raven Coloured Progressive Matrices (36) 24 22 18
Memory
WAIS forward digit span (9) 6 5 5
Corsi block tapping (7) 5 4 4
Rey AVLT
Total (75) 35 21 18
Long term (15) 6 3 2
Recognition (15) 14 10 5
Rey figure B test (recall) (31) 29 26 25
Visuoperceptual functions
Benton line orientation test (30) 25 21 19
Praxis
De Renzi test
Ideational (20) 20 18 18
Ideomotor (20) 20 20 20
Orobuccal (20) 20 16 16
Constructional (20) 20 20 18
Attention and executive functions
WCST category (6) 5 2 0
Weigl’s sorting test (15) 11 7 2
Luria motor sequences (30) 27 20 11

For each single test, the maximum score is reported in parentheses. MMSE = Mini-Mental
State Examination; WAIS = Wechsler Adult Intelligence Score; AVLT = auditory verbal lear-
ning test; WCST = Wisconsin Card Sorting test.

entity whose clinical characteristics are the aphasic pre-
senting problem, severe bulbar involvement of MND,
rapid progression and a short duration of the disease [4].
As a matter of fact, the Lund and Manchester Groups pro-
posed already in 1994 that cases of MND and aphasic
dementia should be considered as a subgroup of the fron-
totemporal dementias (FTDs) [5]. Alternatively, some
authors have considered MND in association with apha-
sic dementia to represent a heterogeneous syndrome with-
in which dysphagia is due to the oral apraxia that is fre-
quently associated with aphasia [6], and the cognitive
symptoms are explained by an atypical distribution of
Alzheimer’s disease neuropathology [2].
We report the case of a 71-year-old man with a 15-
month history of progressive aphasic dementia and bul-
bar MND. In this patient, we performed detailed neuro-
psychological assessments at 3, 9 and 15 months after the
onset of the disease, extensive neuro-imaging evaluation –
magnetic resonance imaging (MRI), proton magnetic res-
onance spectroscopy (1H-MRS) and single-photon emis-
sion computed tomography (SPECT) – and post-mortem
examination. The clinico-pathological features and the
evolution of this rare syndrome are described in light of
the pertinent literature.
Case Report
A 71-year-old, right-handed male presented with a 3-month histo-
ry of progressive word-finding problems. Physical and neurological
examinations were normal. Biochemical, haematological and sero-
logical tests were also normal. His past medical history was unre-
markable except for a recent mild increase in blood pressure values.
He was on no medication.
Over the following months, his speech output reduced drastically
to a few repetitive words, and comprehension became impaired. He
developed a certain difficulty in swallowing, particularly for solid
food, and subsequently he developed dysarthria. At this point, neuro-
logical examination showed rare spontaneous fasciculations of his
tongue and back with no other abnormalities. A barium meal study

22 Dement Geriatr Cogn Disord 2004;17:21–28 Catani/Piccirilli/Geloso/Cherubini/Finali/

Pelliccioli/Senin/Mecocci
Table 2. Language assessment
January 2001 June 2001 December 2001

Token test (36) 30 21 12

Fluency
Letter (25.9B9.2) 10 9 3
Category (30.1B7.6) 27 18 9
Battery for analysis of aphasic deficits (100%)
Conversational speech 60 30 10
Articulation 100 70 –
Naming
Oral
Pictures 90 70 30
Actions 80 50 20
Description 70 40 10
Written
Pictures 90 60 20
Repetition
Words 100 90 –
Sentences 100 80 –
Comprehension
Oral
Words 90 60 20
Semantic task 80 40 20
Syntactic task 40 20 10
Written
Words 90 50 20
Sentences 90 30 10

The maximum score is reported in parentheses; these values represent normal ranges.

of the upper digestive tract was normal. The neurophysiological
examination showed signs of generalized denervation with normal
motor and sensory nervous conduction. An electro-encephalogram
was normal.
Dysphagia became progressively severer so that he could only
swallows fluids. He became irritable, but his family felt that his per-
sonality was reasonably unaltered except for a depressed mood.
Snout reflex and bilateral palmomental reflex were present. He
seemed to have insight into his problems. One year after the onset of
the disease, he became mute with severe dysphagia so that a naso-
gastric tube was placed. Fasciculations at that time were widespread,
although strength in the four limbs was preserved. He died of bron-
chopneumonia 15 months after the onset of the disease.
Neuropsychological Assessment
Cognitive function was examined using a standardized
battery of neuropsychological tests for the assessment of
general intellectual ability (Mini-Mental State Examina-
tion and the Coloured Progressive Matrices test), lan-
guage (Token test, Letter and Category Fluency test,
Milan Language Examination test, Battery for Analysis of
Aphasic Deficits), praxis (De Renzi test for oral, ideation-
al, ideomotor and constructional apraxia), visuopercep-
tual functions (Benton test of line orientation), verbal
memory and learning (WAIS forward digit span, Rey
auditory verbal learning test), non-verbal memory and
learning (Corsi block tapping test, Rey Figure B – recall)
as well as attentional and executive functions (Stroop test,
Luria Motor Sequences, Wisconsin Card Sorting test). All
tests were administered according to standardized proce-
dures and scoring systems [7–14]. Neuropsychological
examination was performed 3 times during the course of
the disease (tables 1, 2).
The patient had a progressive and rapid decline of cog-
nitive function with a severer impairment of language
abilities than visuospatial abilities.
On the first examination (January 2001) the patient
reported a word-finding problem and found it difficult to

Aphasic Dementia with MND Dement Geriatr Cogn Disord 2004;17:21–28 23

follow conversation. Spontaneous language was very im-
poverished (i.e. the richness and complexity of statements
was reduced). Examination revealed a selective language
problem, with normal scores in other cognitive tests.
Fluency was particularly reduced and the marked defi-
ciency of syntactic words made the output strikingly
abnormal. Anomia, circumlocutions, verbal stereotypy
and repetition of groups of syllables were present. Naming
was impaired particularly for verbs. Repetition and trans-
coding abilities were normal. Comprehension of grammar
structures was clearly compromised, while word compre-
hension was relatively spared. There was no dysarthria or
orofacial apraxia.
After 6 months, the language problems had progressed,
and dysarthria together with mild orofacial apraxia be-
came evident. Evaluation of verbal memory was difficult
due to the language problems; nevertheless, its impair-
ment, suggested by the patient’s daily behaviour, was sup-
ported by the score on the recognition test. Executive
functions were more impaired than in the first examina-
tion. On the other hand, non-verbal tests, such as con-
structional praxis and the Benton test of line orientation,
were normal.
The final examination (performed in December 2001)
showed a further deterioration of cognitive performances.
However, non-verbal functions remained comparatively
less impaired than verbal abilities. Behavioural distur-
bances, such as irritability and emotional lability, ap-
peared in the last phase of the disease, when the patient
was also extremely depressed.
Neuro-Imaging Studies
MRI and 1H-MRS were carried out by a clinical 1.5-
tesla MR system (Sigma Advantage, GE Medical System)
using the standard head coil. Sagittal and coronal fast-
spin echo T1-weighted images (TR/TE/excitations 540/
18/2, echo train length 2), axial-oblique SE PD/T2-
weighted images (TR/TE/excitations 2,500/30–100/1),
coronal T2-weighted fast-spin echo images (TR/TE/exci-
tations 4,000/100/3, echo train length 8) were acquired
with 5 mm slice thickness, 1 mm gap, acquisition matrix
256 ! 256, field of view 24 ! 24. Additional axial fast
fluid-attenuated inversion recovery images (TR/TE/exci-
tations 7,155/112/1) were acquired in order to localize the
regions of interest (ROIs) for spectrum recordings. 1H-
MRS (Press pulse sequence; TE = 40 ms; TR = 2,000 ms)
was used to acquire spectra from two 2 ! 2 ! 2 volumes
of interest (VOIs) located in the white matter of the anteri-
24 Dement Geriatr Cogn Disord 2004;17:21–28
or temporal lobe. The spectrum processing included: free
induction decay apodization, fast Fourier transformation
and frequency domain fitting using the Marquardt-Lev-
enberg algorithm. The N-acetylaspartate creatine, myo-
inositol/creatine and choline/creatine ratios were calcu-
lated bilaterally [15].
To perform the SPECT, the patient was injected with
500 MBq of 99Tc-hexamethylpropylene amine oxime
(HMPAO), and data were acquired on a Gamma 11 com-
puter system. Frontal, temporoparietal and temporo-oc-
cipital ROIs were defined on computed tomography
scans, and their activities were compared with the activity
of the cerebellar ROI.
Cortical-subcortical atrophy with mild left perisilvian
predominance was evident on MRI (fig. 1, upper row).
SPECT using 99Tc-HMPAO revealed a significantly re-
duced uptake of tracer in the left frontal (–10%) and left
temporal regions (–6%; fig. 1, lower row).
1H-MRS showed asymmetry in brain metabolite lev-
els. Myo-inositol/creatine and choline/creatine ratios
were increased in the left VOI (0.80 and 0.76, respective-
ly) compared to the right (0.69 and 0.67, respectively). N-
acetylaspartate/creatine levels were similar in the 2 VOIs
(right, 1.30; left, 1.28). Lactate was not present.
Histopathological Studies
The brain was fixed in 10% formalin solution for 6
weeks and then cut coronally into 2-cm slices. After gross
examination, tissue blocks from both right and left hemi-
spheres were taken from prefrontal, motor, temporal,
superior parietal, anterior cingulate, hippocampal and
occipital cortices. We also examined the striatum, thala-
mus, midbrain and spinal cord. Blocks were processed
routinely into paraffin wax and 7-Ìm sections were
stained with haematoxylin-eosin and Luxol fast blue-cre-
syl violet for routine neuropathological examination.
Immunocytochemical investigations were performed
on sections from all these regions using the following pri-
mary antibodies: anti-ubiquitin (polyclonal, Sigma, 1:50),
anti-Ù (monoclonal, clone 2, Sigma; 1:100), anti-ß-protein
(polyclonal, Sigma; 1:100), anti-glial-fibrillary-acidic-pro-
tein (GFAP; polyclonal, Dako, Glostrup, Denmark;
1:100), anti-prion-protein 3F4 (monoclonal, Senetek,
Maryland Heights, Mo., USA; 1:250). The binding of the
primary antibody was detected using a biotinylated sec-
ondary antibody and an avidin-biotin-peroxidase method
(ABC Elite, Vector Laboratories, Burlingame, Calif.,
USA) with diaminobenzidine as substrate. All sections
Catani/Piccirilli/Geloso/Cherubini/Finali/
Pelliccioli/Senin/Mecocci
 Fig. 1. Coronal (A), sagittal (B) and axial (C) T1-weighted (upper row) and SPECT (lower row) images. Mild asym-
metric perisylvian cortical atrophy and reduced perfusion in the left frontal and temporal lobes.
were counterstained with haematoxylin. For prion pro-
tein immunostaining, paraffin sections were mounted on
silanized slides (Dako), and for the avidin-biotin peroxi-
dase method with formic acid, guanidine thiocyanate and
autoclaving pretreatments were used.
At gross examination no significant atrophy was evi-
dent. The cerebral cortex, basal ganglia, thalamus, cere-
bellum and pigmented midbrain and pontine nuclei ap-
peared normal. Macroscopic examination showed only a
thinning of the anterior part of the corpus callosum. His-
tological examination revealed microvacuolar change and
mild neuronal loss localized in layer II of the cortical lami-
nae at the frontoparietotemporal level (fig. 2A). A mild
astroglial reaction was evident in the subpial regions and
at the border between grey and white matter (GFAP
immunostaining). Dot-like ubiquitin-positive deposits
were seen in the cortical neuropil.
A severe neuronal loss was evident in ·-motor nuclei of
the medulla oblongata (hypoglossal nucleus) and cervical
tract of the spinal cord (fig. 2B, C). The long white matter
tracts within the spinal cord and brain stem appeared well
myelinated. Some skein or rounded ubiquitin-positive
Aphasic Dementia with MND
and Ù-negative inclusions were found within some of the
remaining ·-motor neurones in the same regions (fig. 2D).
Neither Ù-positive neurofibrillary tangles nor ß-protein-
positive plaques were found in the samples studied. No
immunoreaction was found with anti-prion-protein 3F4
antibody. All the pathological changes were bilateral with
no side prevalence.
Discussion
The patient reported in this study exemplifies the syn-
drome of MND with rapidly progressive aphasic demen-
tia, as described by Caselli et al. [1]. The disorder is a rare
condition affecting both men and women. Our patient
presented the first symptoms at 71 years of age, but the
disease typically begins a decade earlier (mean age of
onset 62 years with a range of 43–77). The duration of
illness is fairly short, about 2–3 years, and death is gener-
ally due to respiratory failure consequent to aspiration
pneumonia [1–4, 16].
Dement Geriatr Cogn Disord 2004;17:21–28 25
 Fig. 2. A Microvacuolar degeneration in layer II of the frontal cortex. There is only mild neuronal loss. Haematox-
ylin-eosin staining. Magnification !200. B Severe neuronal loss from the hypoglossal nucleus. Haematoxylin-eosin
staining. Magnification !100. C Severe neuronal loss in the anterior horn of the cervical spinal cord. Luxol fast
blue-cresyl violet staining. Magnification !40. D Ubiquitin-positive neuronal inclusion in the cervical spinal cord.
Ubiquitin immunocytochemistry. Magnification !400.

In our patient, the serial neuropsychological assessment
describes the progression of the cognitive deficits. In most
of the cases, cognitive symptoms are the initial clinical pre-
sentation with neurological signs appearing at the same
time [2, 3] or later, usually after 6–12 months [1, 2 4]. The
presenting and dominant feature of the cognitive deficits is
a progressive, non-fluent aphasia that the patients describe
as a ‘word-finding problem’. Initial formal examination of
language suggests a transcortical motor aphasia. As the dis-
ease progresses, the aphasic component, both in spoken and
written language, involves also the comprehension. The
patients have difficulty not only with comprehending syn-
tactically complex sentences, but also with single-verb com-
prehension. This characteristic has recently been recog-
nized as a distinctive feature of MND with aphasia-demen-
tia where the selective impairment of verb processing may
be related to the disruption of anterior frontal parts of the
language system [4]. As the disease progresses, language
deficits become generalized and other frontal-lobe-de-
pending cognitive functions are affected. However, non-
verbal skills appear more preserved.
The majority of cases of MND and aphasic dementia
show psychiatric features consistent with frontotemporal
dementia, characterized by personality change, irritabili-
ty, apathy, rigidity of behaviour and thinking [2, 4]. In our
patient, mild behavioural disturbances, such as irritabili-
ty and emotional lability, appeared in the last phase of the
disease. In fact, major personal and behavioural altera-
tions are characteristic of the MND and FTD association
rather than MND and aphasic dementia [17–19].
Neurological signs and symptoms are usually different
from patients with typical MND. Bulbar deficits start ear-
ly, progress rapidly and are the major source of disability
and mortality [1]. Both lower and upper MND signs are
evident, but the degree of limb weakness and muscle atro-
phy is variable and usually much milder than bulbar dys-

26 Dement Geriatr Cogn Disord 2004;17:21–28 Catani/Piccirilli/Geloso/Cherubini/Finali/

Pelliccioli/Senin/Mecocci
function [1, 2, 4]. EMG evidence of denervation is always
present [1–4]. Frontal release signs (positive snout and
grasp responses) are frequently observed [1, 2, 4].
The neuro-imaging alterations seen in our patient
showed a left frontotemporal asymmetry, more evident
on SPECT images. Considering the cases from the litera-
ture, structural brain imaging (CT or MRI) examination
has been performed in 20 patients and revealed left fron-
tal or temporal atrophy (12 patients), mild general atro-
phy (4 patients) and bilateral frontal or frontotemporal
atrophy (2 patients) [1–4, 16]. Only 1 patient had normal
brain imaging [4]. Functional imaging (SPECT) has been
performed in 11 patients and revealed bilateral (6 pa-
tients) or left hypoperfusion (5 patients) [1, 2, 4]. A consis-
tent feature is focal involvement of the temporal (8
patients) or frontal lobe (7 patients) or both (5 patients).
One patient only showed parietal hypoperfusion [4]. An
electro-encephalogram is usually normal [1, 2, 4, 13],
although non-specific dysrhythmic slowing is reported in
2 patients [1]. In our patient, we performed 1H-MRS of
the anterior temporal lobe. We found a left temporal lobe
increase in myo-inositol/creatine and choline/creatine ra-
tios which are indicative of an asymmetric temporal lobe
involvement. This technique, that allows to quantify
brain metabolites in vivo, has shown white matter metab-
olite changes in neurodegenerative diseases such as Alz-
heimer’s disease [20] and MND [21]. Similar asymmetri-
cal changes have been demonstrated in patients with pri-
mary progressive aphasia without MND [22].
Neuropathological examination has been performed in
11 subjects [1–4, 16]. A mild to moderate frontal atrophy
is reported in 8 patients (in 2 it was more pronounced on
the left) and a left temporal atrophy in 7 cases. The spinal
cord showed atrophy of the ventral nerve roots [1, 4]. His-
tologically, changes characteristic of both FTD and MND
alone are seen. In the affected frontal, temporal and pari-
etal cortex, in addition to the microvacuolar type of
degeneration (typical of FTD, but usually rather milder in
extent), there are intraneuronal inclusions [23]. These are
characteristically seen in layer II neurons and are ubiqui-
tin but not Ù immunoreactive [3, 4]. This characteristics
distinguishes these bodies from the Pick type of inclu-
sions, which are both Ù and ubiquitin immunoreactive
[23]. Like classic MND, the characteristic ubiquitin inclu-
sions can be seen in MND with aphasic dementia within
the motor neurons of the anterior horns of the spinal cord
and brain stem cranial nerve nuclei [3, 4, 23]. The severe
loss of neurones on the hypoglossal nucleus and the anteri-
or cervical horns is observed in most of the patients [1, 3,
4] but not in all [1, 16].
Aphasic Dementia with MND
In our case, the bilateral and widespread pathological
changes seem to be in contrast with the clinical and neuro-
imaging findings of a more localized and lateralized disor-
der. However, if we consider the progression of the dis-
ease as documented by the neuropsychological assess-
ments, it is possible to recognize an early localized onset
of disease compatible with the neuro-imaging data and a
later more advanced widespread phase compatible with
the post-mortem findings.
Although the majority of FTD-MND cases occur spo-
radically, several familial cases have also been reported
[for a review, see 24]. A possible linkage with chromo-
some 9q21–q22 has been identified in FTD-MND fami-
lies but not in MND alone [25]. No genetic data have been
published on families with MND and aphasia.
In conclusion, rapidly progressive aphasic dementia
with MND is a rare degenerative disorder of the central
nervous system that represents a distinctive clinical entity
within the FTD-MND spectrum. We reported for the first
time the use of 1H-MRS in this syndrome that allowed
demonstrating an in vivo asymmetric change in brain
metabolite levels. Furthermore the extensive neuropsy-
chological evaluation over 1 year of this patient permitted
us to understand in detail the pattern of progression of the
disease. Finally, the comparison of clinical and neuro-
imaging findings with neuropathological results showed
that the clinical focality of the aphasic cognitive disorder
and MND is matched by the anatomical selectivity of the
underlying pathological process that affects primarily the
cortical areas of language, the hypoglossal nuclei and the
anterior horn of the cervical spinal cord.
Acknowledgements
We gratefully thank Dr. Pietro Chiarini and Roberto Tarducci for
the MRI and 1H-MRS analysis, Dr. Gian Franco Perticoni and Dr.
Alessandro Bartocci for their suggestions on the interpretation of the
EMG pattern and Michele Di Bari for his excellent technical assis-
tance. We also wish to thank Prof. Robert Howard for the revision of
the manuscript and the Centre for the Creutzfeldt-Jakob disease sur-
veillance, Laboratory of Virology, Istituto Superiore di Sanità,
Rome, Italy.
Dement Geriatr Cogn Disord 2004;17:21–28 27
 References
1 Caselli RJ, Windebank AJ, Petersen RC, Ko-
mori T, Parisi JE, Okazaki H, Kokmen E, Ie-
verson R, Dinapoli RP, Graff-Radford NR,
Stein SD: Rapidly progressive aphasic demen-
tia and motor neuron disease. Ann Neurol
1993;133:200–207.
2 Doran M, Xuereb J, Hodges JR: Rapidly pro-
gressive aphasia with bulbar motor neurone
disease: A clinical and neuropsychological
study. Behav Neurol 1995;8:169–180.
3 Tsuchiya K, Ozawa E, Fukushima J, Yasui H,
Kondo H, Nakano I, Ikeda K: Rapidly progres-
sive aphasia and motor neuron disease: A clini-
cal, radiological, and pathological study of an
autopsy case with circumscribed lobar atrophy.
Acta Neuropathol (Berl) 2000;99:81–87.
4 Bak TH, O’Donovan DG, Xuereb JH, Boni-
face S, Hodges JR: Selective impairment of
verb processing associated with pathological
changes in Brodmann areas 44 and 45 in the
motor neurone disease-dementia-aphasia syn-
drome. Brain 2001;124:103–120.
5 Brun A, Englund B, Gustafson L, Passant U,
Mann DMA, Neary D, Snowden JS: Consensus
statement: Clinical and neuropathological cri-
teria for frontotemporal dementia. J Neurol
Neurosurg Psychiatry 1994;57:416–418.
6 Fuh JL, Liao KK, Wang SJ, Lin KN: Swallow-
ing difficulty in primary progressive aphasia: A
case report. Cortex 1994;30:701–705.
7 Folstein MF, Folstein SE, McHugh PR: ‘Mini-
mental state’: A practical method for grading
the cognitive state of patients for the clinician.
J Psychiatr Res 1975;12:189–198.
8 Lezak MD: Neuropsychological Assessment.
Oxford, Oxford University Press, 1995.
28 Dement Geriatr Cogn Disord 2004;17:21–28
9 Miceli G, Burani C, Laudanna A: Batteria per
l’analisi dei deficit afasici. Milano, ASRN,
1991.
10 Piccirilli M, Piccinin GL, D’Alessandro P, Pic-
cinin GL, Agostini L: Frontal lobe dysfunction
in Parkinson’s disease. Eur Neurol 1989;29:
71–76.
11 Spinnler H, Tognoni G: Italian standardization
and classification of neuropsychological tests:
The Italian Group on the Neuropsychological
Study of Aging. Ital J Neurol Sci 1987;8:1–
120.
12 Raven JC: Revised Manual for Raven’s Pro-
gressive Matrices and Vocabulary Scale. Wind-
sor, NFER Nelson, 1982.
13 Rey A: L’examen clinique en psychologie. Pa-
ris, Presses Universitaires de France, 1964.
14 Benton AL, Hamsher K, Varney NR, Spreen
O: Contributions to Neuropsychological As-
sessment: A Clinical Manual. Oxford, Oxford
University Press, 1983.
15 Catani M, Cherubini A, Howard R, Tarducci
R, Pelliccioli GP, Piccirilli M, Gobbi G, Senin
U, Mecocci P: 1H-MR spectroscopy differen-
tiates mild cognitive impairment from normal
brain aging. Neuroreport 2001;12:2315–2317.
16 Kirshner HS, Tanridag O, Thurman L, Whet-
sell WO: Progressive aphasia without demen-
tia: Two cases with focal spongiform degenera-
tion. Ann Neurol 1987;22:527–532.
17 Neary D, Snowden JS, Mann DM, Northen B,
Goulding JP, Macdermott N: Frontal lobe de-
mentia and motor neuron disease. J Neurol
Neurosurg Psychiatry 1990;53:23–32.
18 Peavy GM, Herzog AG, Rubin NP, Mesulam
MM: Neuropsychological aspects of dementia
of motor neuron disease: A report of two cases.
Neurology 1992;42:1004–1008.
19 Rakowicz WP, Hodges JR: Dementia and
aphasia in motor neuron disease: An under-
recognised association? J Neurol Neurosurg
Psychiatry 1998;65:881–889.
20 Adalsteinsson E, Sullivan EV, Kleinhans N,
Spielmann DM, Pfefferbaum A: Longitudinal
decline of the neuronal marker N-acetyl aspar-
tate in Alzheimer’s disease. Lancet 2000;355:
1696–1697.
21 Pohl C, Block W, Karitzky J, Schmidt S, Pels
H, Grothe C, Schild HH, Klockgether TH: Pro-
ton magnetic resonance spectroscopy and
transcranial magnetic stimulation for the de-
tection of upper motor neuron degeneration in
ALS patients. Arch Neurol (Chicago) 2001;58:
729–735.
22 Catani M, Piccirilli M, Cherubini A, Tarducci
R, Sciarma T, Gobbi G, Pelliccioli GP, Petrillo
MS, Senin U, Mecocci P: Axonal injury within
language network in primary progressive apha-
sia: A 1H-MR spectroscopy study. Ann Neurol
2003;53:242–247.
23 Mann DM: Dementia of frontal type and de-
mentias with subcortical gliosis. Brain Pathol
1998;8:325–338.
24 Bak T, Hodges JR: Motor neurone disease,
dementia and aphasia: Coincidence, co-occur-
rence or continuum? J Neurol 2001;248:260–
270.
25 Hosler BA, Siddique T, Sapp PC, Sailor W,
Huang MC, Hossain A, Daube JR, Nance M,
Fan C, Kaplan J, Hung W-Y, McKenna-Yasek
D, Haines JL, Percak-Vance MA, Horvitz HR,
Brown RH: Linkage of familial amyotrophic
lateral sclerosis with frontotemporal dementia
to chromosome 9q21–q22. JAMA 2000;284:
1664–1669.
Catani/Piccirilli/Geloso/Cherubini/Finali/
Pelliccioli/Senin/Mecocci