-
32ournal ofNeurology, Neurosurgery, and Psychiatry
1995;59:312-315
SHORT REPORT
Slowly progressive apraxia in Alzheimer's disease
R C Green, F C Goldstein, S S Mirra, N P Alazraki, J L Baxt, R A
E Bakay
AbstractSlowly progressive apraxia due toAlzheimer's disease was
encountered ina 66 year old, right handed man whoseinitial
impairments included coordinatedmovements of the left hand and
somefeatures of the alien hand syndrome.Over four years, the
patient developedprogressively worsening deficits ofmem-ory and
language. A biopsy of his righttemporal lobe showed numerous
plaquesand neurofibrillary tangles. Pronouncedright parietal lobe
hypoperfusion on ser-ial SPECT suggests involvement of thisregion
in contralateral praxis.
( Neurol Neurosurg Psychiatry 1995;59:312-315)
Keywords: Alzheimer's disease; subtypes; apraxia;movements
NeurobehavioralProgram, WesleyWoods Center andDepartment
ofNeurology, VAMedical CenterR C GreenF C GoldsteinGwinnett
NeurologyClinicJ L BaxtDepartment ofPathology andLaboratory
MedicineS S MirraDepartment ofNeurosurgery, EmeryUniversity
HospitalR A E BakayDepartment ofNuclear Medicine,Emergy
UniversitySchool ofMedicine,Atlanta, Georgia, USAN P
AlazrakiCorrespondence to:Dr Robert C Green, WesleyWoods Center,
1841 CliftonRoad, NE Atlanta, GA30329, USA.Received 21 March
1994and in final revised form2 May 1995Accepted 9 May 1995
Apraxia is a syndrome of impaired executionof learned skilled
movements that cannot beexplained by weakness, incoordination,
sen-sory loss, lack of comprehension, or inatten-tion. Apraxia is
common in Alzheimer'sdisease, usually appearing after impairmentsof
memory and language are established. Afew cases of slowly
progressive apraxia with-out deficits in memory and language
havebeen described but the underlying pathologywas not
established.l1 Our patient showedprogressive apraxic symptoms early
in thecourse of his illness.
Patient historyA 66 year old, right handed, college
educatedchemical engineer experienced the insidiousonset of finger
and hand incoordination inassociation with complex movements of
theleft hand at the age of 60. Initially, he hadminor problems
driving his car and shufflingplaying cards, but by the end of 1988
he hadstopped working and could not easily tie hisshoelaces, button
his shirt, or eat with his lefthand. He and his family denied any
languageor memory difficulties. When initially exam-ined in June
1990 the patient was aware ofhis deficits, stating that his left
hand "seemsto have a life of its own." His wife confirmedextraneous
behaviours reminiscent of alienhand syndromes, such as placing a
napkin inhis lap with his right hand, only to have his
left hand reach out and remove it. After sixmonths, he had
problems performing mentalarithmetic, writing script or numbers
with hisright hand, and he experienced spatial confu-sion when
driving or in a familiar environ-ment without visual cues. He and
his wifeagreed that he still did not have problemswith gait, word
finding, comprehension, ormemory. There was no personal or
familyhistory of neuropsychiatric problems or sub-stance misuse,
except for a maternal auntclinically diagnosed as having
Alzheimer'sdisease. Detailed neurological examinationwas normal,
including motor tone and pri-mary sensory and motor function in
thelimbs, except for moderately severeagraphaesthesia and
astereognosis in the lefthand and difficulties with left hand
praxis.
Neuropsychological evaluations were con-ducted in July 1990,
January 1991, and July1992 (table). Apraxia was evaluated by
hav-ing the patient carry out gestures and imag-ined use of
objects. When seen in July 1990,imitation was performed poorly by
each handand the execution of transitive and intransi-tive
movements to command was worse withthe left hand. Responses were
slow, and bodypart as the object and spatial displacementswere
common. Performance did not appre-ciably improve when the patient
was testedwith actual objects. At his six month followup, there was
a noticeable deterioration oftransitive and intransitive movements
withthe right hand. Imitation was still poor bilat-erally, and had
become even worse with theleft hand. By July 1992 he could only
performsimple right handed movement to commandand imitation, and he
could not execute anymovements with his left hand.
In July 1990 he could not determine howto hold a pencil with his
left hand and hecould not write a sentence correctly to dicta-tion
with his right hand, although he couldcopy. By January 1991, his
writing with hisright hand both to dictation and from
copydeteriorated and by July 1992 he was unableto write his name.
His drawings were tremu-lous and micrographic, and he was
impairedin copying simple geometric designs on theBenton visual
retention test. By contrast withhis dyspraxic and dysgraphic
symptoms, hislanguage abilities were relatively preserved inJuly
1990 and January 1991. By July 1992,however, he displayed severe
dysnomia, withmany perceptual misidentifications andsemantic
paraphasias. Generation of words
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Slowly progressive apraxia in Alzheimer's disease
Neuropsychological test results
July 1990 January 1991 July 1992
Intellectual functioning:(WAIS-R: mean = 100, SD = 15)
Verbal IQ 109 110 69Performance IQ 63 60 60Full Scale IQ 88 87
63
Verbal age scaled scores:(mean = 10, SD = 3)
Information 14 14 1Digit span 8 5 3Vocabulary 14 14 11Arithmetic
4 4 2Comprehension 12 16 8Similarities 16 16 3
Performance age scaled scores:Picture completion 3 4 2Picture
arrangement 6 2 2Block design 2 2 3Digit symbol 2 1 1
Language:Apraxia (No correct)Limb intransitive (12 total):RH:
commands 8 6 1
Imitation 9 9 0LH: commands 2 3 0
Imitation 8 4 0Limb transitive (7 total):RH: commands 5 2 0
Imitation 4 3 0LH: commands 2 2 0
imitation 6 4 0Writing (No correct/6 words)
Dictation (RH, LH) 2, CND 3, CND CND, CNDCopy (RH, LH) 6, CND 4,
CND CND, CND
Naming (No correct/60 pictures) 55 55 10Verbal fluency (No
correct)
Three letters 26 20 0Three categories 46 33 9
Tactile naming (14 objects)RH (No correct) 12 10 NGLH (No
correct) 8 10 NG
Memory:Picture recognition
(No correct/100) 78 67 CNDStory recall
(No units/50) 8 0 0Story recognition
(No units/20) 14 13 6/13
CND = could not do; NG = not given; LH = left hand; RH = right
hand.
beginning with specific letters was in the lowto normal range at
his initial session, anddeteriorated further in subsequent
examina-tions.When initially tested, the patient's visual
recognition memory was in the low averagerange. Six months
later, there was a notice-able decline, and by July 1992 he could
notperform the task. Over the two years he wasfollowed up he
exhibited a steady decline inhis verbal intellectual abilities. The
tableshows a pronounced difference between hisaverage verbal IQ and
severely impaired per-formance IQ in July 1990 and January 1991.By
July 1992 the verbal IQ had dropped 40points, and he had lost the
insight that hadcharacterised his earlier testing sessions.
Diagnostic testing in the summer of 1990and the winter of 1991
included 1-5 TeslaMRI showing only generalised atrophy, amoderately
abnormal EEG, with diffusebackground slowing, and normal routine
lab-oratory studies including thyroid functiontests, vitamin B12
concentration, and sedi-mentation rate. A lumbar puncture
showednormal opening pressure, acellular fluid witha normal glucose
concentration, and a slightlyraised protein of 54 mg/dl. SPECT was
per-formed 20 minutes after intravenous injectionof 20 mCi
technetium-99 m hexamethyl-
propyline amineoxime with the patient supinein a low stimulation
environment in August1990 and February 1991. These studiesshowed
hypoperfusion in the right frontal,parietal, temporal, and
occipital regions(fig 1).
In February 1991, biopsies of the middleand inferior temporal
cortices on the rightside were performed.
Neuropathologicalexamination with Bielschowsky silver stainingof
the paraffin embedded material showednumerous senile plaques (up to
50 per lowpower field) (fig 2). The plaques were pre-dominantly
neuritic in nature, some contain-ing amyloid cores; a few diffuse
plaques werealso seen. The density of neuritic plaques
metconventional neuropathological criteria fordiagnosis of
Alzheimer's disease.5 Numerousneurofibrillary tangles were also
noted, partic-ularly in the deeper layers of cortex, alongwith
neuropil threads.
DiscussionApraxia is common in dementia, occurring
inHuntington's disease, corticobasal ganglionicdegeneration, and
occasionally in Parkinson'sdisease. Apraxia is also common
inAlzheimer's disease, but is rarely described asa presenting
symptom. Three cases of slowlyprogressive apraxia without tissue
diagnoseshave been reported, but two of these seemedto represent
visual agnosias in which thepatients made errors imitating gestures
butperformed correctly to command.6 The thirdcase, a patient with
an insidious loss of abili-ties to perform limb and axial movements
toboth imitation and command, more closelyresembles our patient,
but there was no fol-low up or tissue diagnosis.
Patients with Alzheimer's disease estab-lished by biopsy have
presented with progres-sive left sided clumsiness,
astereognosis,agraphaesthesia, and choreoathetoid move-ments7 as
well as with alien left hand andmyclonus.8 Several other recent
clinical casereports of slowly progressive apraxia havebeen
associated with unilateral or bilateralcortical atrophy and
diminished SPECTactivity in parietal regionslA but none of
thesereports included a tissue diagnosis. Publishedreports of SPECT
findings in patients withAlzheimer's disease indicate that parietal
lobehypoperfusion is often seen, but it usuallypresents
bilaterally. Unilateral apraxia hasoften been described in patients
with focallesions, particularly strokes, but is alsounusual in
Alzheimer's disease.
Apraxia of the non-dominant limb may bea result of
interhemispheric disconnectionassociated with lesions of the corpus
callosumfibres,9 and is often, but not exclusively, asso-ciated
with left hemispheric lesions and withaphasia.'q Although it is
less frequent,apraxia can also occur after right
hemisphericlesions,I"13-19 raising the possibility that
thevisuokinaesthetic engrams containing spatialand temporal
representations of leamedmovements may occasionally be
representedeither bilaterally or in the non-dominant
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Green, Goldstein, Mirra, Alazraki, Baxt, Bakay
Figure 1 SPECT axial(above), sagittal (lowerleft) and coronal
(lowerright) slices of technetium-99 m HMPAO brainperfusion scans
fromFebruary 1991 showdeficient cerebral perfusionin the right
cerebral cortexin all projections (arrows),most severe in the
posteriorparietal cortex. Perfusionon the left is normal.
hemisphere, and not only in the left hemi-sphere.20 24
There is no way of knowing the full extentof neuropathology in a
living patient withneurodegenerative disease. It is of
interest,however, that this patient presented withprominent
symptoms of the left hand andthat SPECT perfusion images and
quantita-tive analysis showed mild frontal and pro-nounced parietal
hypoperfusion in the righthemisphere, supporting the notion that
theseregions may be salient in contralateral praxis.Indeed, the
praxis system in the right hemi-sphere has been implicated in the
mediationof "concrete" or context dependent perfor-
mance of transitive movements and in learn-ing novel movement
sequences.25 The alienhand features seen in this patient, along
withdysgraphia and impaired tactile naming withthe left hand, are
difficult to explain on thebasis of frontal or parietal lesions
alone andsuggest some degree of interhemispheric dis-connection
early in the disease process.
This work was presented in part to the
InternationalNeuropsychological Society, San Diego, CA, 1992. It
wassupported by the Emory Research Grant Committee, a grantfrom the
Fraternal Order of Eagles, and NIA grantsP30AG10130 (Emory
Alzheimer's Disease Center) andRO1AG11503 (RCG).
Figure 2 Bielschowsky(silver) stain ofparaffinembedded
materialfrom aright temporal lobe biopsyshows three neuriticplaques
and multipleneurofibrillary tangles(arrows). Originalmagnification
x 125.
z)* R W e
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Chaulmoogra (Hydnocarpus wightiana)
The seeds of the fruit of the chaulmoogra tree containstrongly
antibacterial chemicals, two of which, hydno-carpic and
chaulmoogric acids, destroy the bacteriumMyobacterium leprae.
Ancient Hindu and Chinese docu-ments described an oil that was
effective against leprosy,and it is likely that this came from the
chaulmoogra tree.Only about the middle of the last century was the
oiltaken seriously by western physicians. It was
investigated,tested, and soon imported from China but the supplywas
severely limited. In some places today, the ingre-dients of
chaulmoogra oil, modified by chemists, are stillused to cure early
cases of leprosy, but advanced cases donot yield to the
treatment.The chaulmoogra tree is shown on a stamp issued by
Fiji in 1970 (Stanley Gibbons 420, Scott 289).L F HAAS
P.ww s w -w w w w w w w mw-@w w w ww w a w Ur
CHAUL.MUGN.^. TR.EE.......... . . .. _x §1>CLOSING OF LEPROSY
HlOSPtTAL MAKOGAIrs^.aLaaaA -,a
NEUROLOGICAL STAMP
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