ANNUAL

REVIEWS Further
Quick links to online content
Ann. Rev. Med.1988. 39:5361

PSYCHOLOGICAL DYSFUNCTION
ACCOMPANYING SUBCORTICAL
DEMENTIAS1
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

Jeffrey L. Cummings, M.D. and D. Frank Benson, M.D.

Neurobehavior Unit, West Los Angeles Veterans Administration Medical

Center (Brentwood Division), Los Angeles, California 90073; and the
Departments of Neurology and Psychiatry & Biobehavioral Sciences,
UCLA School of Medicine, Los Angeles, California 90024

ABSTRACT

Subcortical dementia occurs both in disorders affecting the basal ganglia

(for example, Parkinson's disease, Huntington's disease, and progressive
supranuclear palsy) and in a variety of subcortical vascular, infectious,
inflammatory, neoplastic, and traumatic conditions. The principal features
of subcortical dementia include bradyphrenia, impairment of executive
function, recall abnormalities, visuospatial disturbances, depression, and
apathy. The syndrome contrasts with dementia of the Alzheimer type in
which cortical involvement produces aphasia, combined recall and
recognition deficits, and indifference. Electrophysiologic, biochemical, and
metabolic studies support a distinction between subcortical and cortical
dementias.

INTRODUCTION

Dementia is a syndrome of acquired brain dysfunction manifested by

abnormalities in multiple neuropsychological domains. It is characterized
by persistent deficits in at least three of the following realms of mental
activity: language, memory, visuospatial skills, personality and emotional
function, and cognition (abstraction, mathematics) (1). Investigation of

I The US Government has the right to retain an exclusive, royalty-free license in and to
any copyright covering this paper.

5":1
 54 CUMMINGS & BENSON

the behavioral alterations and neuropsychological abnormalities of the

dementias has revealed two principal patterns of dysfunction. The first
occurs in disorders such as dementia of the Alzheimer type (OAT) and
Pick's disease that involve primarily the cerebral cortex. This pattern has
been labeled "cortical dementia." The principal clinical manifestations
include aphasia, amnesia, apraxia, visuospatial disturbances, and per­
sonality alterations. The second pattern has been called "subcortical
dementia" and occurs in diseases involving the basal ganglia and the
hemispheric white-matter tracts. Subcortical dementia has been described
in degenerative diseases of the basal ganglia (Parkinson's disease, Hun­
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

tington's disease, progressive supranuclear palsy, spinocerebellar degener­

ation, idiopathic basal ganglia calcification), vascular and inflammatory
conditions involving the basal ganglia and thalamus, multiple sclerosis,
and the AIDS-dementia complex. The cardinal features of subcortical
dementia include bradyphrenia (cognitive slowing), memory disturbances,
visuospatial alterations, disproportionate impairment of executive
function, and mood abnormalities. The contrasting clinical profiles of
subcortical and cortical dementias provides valuable information regard­
ing the pathophysiological bases of the dementias. Recent studies address­
ing the differences between cortical and subcortical disorders are reviewed
below.

NEUROPSYCHOLOGICAL MANIFESTATIONS
Bradyphrenia
Bradyphrenia refers to slowing of mental processes and has been suggested
as a synonym for subcortical dementia (2). Bradyphrenia is most thor­
oughly documented in Parkinson's disease, in which cognitive processing
is slower than in control subjects matched for speed of motor activity (3).
In addition, the speed of reaction varies with degree of complexity of the
cognitive task even when the motor demands of the task are held constant
(4).
Cognitive slowing is not evident in the cortical dementias until the final
phases of the illness. Cummings & Benson (5) recently constructed an
inventory of clinical features indicative of OAT and demonstrated that
bradyphrenia is uncharacteristic of cortical dysfunction.

Loss of Executive Functions

Executive functions are complex neuropsychological functions such as
the ability to shift from one idea to another, the ability to predict the
consequences of behavior, and the ability to maintain concentration and
to construct serial goal-directed activities. Behaviorally, deficits in this
 SUBCORTICAL DEMENTIA 55
realm are revealed by lack of foresight and a tendency toward concrete,
literal thought patterns. Neuropsychologically, executive deficits are sug­
gested by poor performance on the Wisconsin Card Sort Test, Odd-Man­
Out Test, concentration and attention tasks, and a variety of motor pro­
gramming tests. Executive functions are mediated by the frontal lobes and
by those subcortical structures with major projections to the frontal cortex
(6); they are disproportionately severely affected in the subcortical
dementias.
Parkinson's disease patients have difficulty shifting from one conceptual
set to another on the Wisconsin Card Sort Test or accurately shifting
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

between two sets of rules on the Odd-Man-Out Test (7, 8). In some cases
these deficits appear before other evidence of intellectual deterioriation is
apparent (9). Other frontal systems tasks performed poorly by Par­
kinsonian patients include cancellation tasks, work list generation, and
motor programming (8-12). Similar deficits havc been identified in Hun­
tington'S disease and in progressive supranuclear palsy (13).
Subcortical-frontal systems also facilitate concentration by providing
control mechanisms that allow freedom from environmental distractions.
When such mechanisms are disrupted, distractability and poor con­
centration result. Distractability is evidenced in subcortical dementia by
abnormalities of cancellation tasks and visual attention tests (14).
In cortical dementia syndromes, executive function deficits are affected
less severely than are other neuropsychological disturbances. PilIon and
coworkers (15) compared patients with DAT, Parkinson's disease, and
progressive supranuclear palsy. The patients were matched for overall
dementia severity but the patient groups exhibited different profiles of
neuropsychological impairment. Notably, progressive supranuclear palsy
patients evidenced more marked frontal systems dysfunction than DAT
patients. The former manifested more inertia, stereotypy, disinterest, and
indifference to rules and had less mental control.
Thus, while present in all types of dementias, executive deficits are
characteristic of subcortical dementia and are proportionately more severe
in these disorders than in the cortical dementias. Disturbances of executive
function and bradyphrenia appear to underlie many of the abnormalities
noted in subcortical dementia, including memory, cognitive, and visuo­
spatial deficits.

Memory Disturbances
Memory abnormalities occur in both subcortical and cortical dementias,
but differences in the type of memory disturbance may be evident on
examination. Neuropsychological investigations in Huntington's disease
show that the primary defect is one of recalling information; patients profit
 56 CUMMINGS & BENSON

by strategies that help them encode the stimulus material for later recall,
and clues aid the patient in recalling learned information (16-18). Similarly,
in Parkinson's disease, acquisition memory (as revealed by paired associate
learning and superspan list learning) is impaired, whereas recognition
memory is unaffected (19-21).
In contrast to patients with subcortical dementias, DAT patients have
more difficulty encoding information for later retrieval and are aided little
by encoding strategies (16, 22, 23). The memory disturbance of DAT is
also disproportionately more severe than that exhibited by patients with
subcortical dementia, even when the patients are matched for overall
dementia severity (15).
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

Visuospatial Abnormalities
Assessment of visuospatial deficits in subcortical dementias is difficult;
many of the available tests involve motor responses and cannot be utilized
in patients with psychomotor retardation, poor coordination, or a move­
ment disorder. Recently, however, a variety of motor-free visuospatial
tasks have been developed that allow investigation of the impact of basal
ganglia disease on visuospatial function. Villardita et al (24) utilized a
developmental test of visual perception to demonstrate that patients with
Parkinson's disease make errors on tasks of distinguishing figure-ground
relationships, determining spatial positions and spatial relationships, and
assessing perceptive constancy. Similarly, Boller and colleagues (25) used
both visuomotor and motor-free visuoperceptual tests to assess visuo­
spatial function in patients with Parkinson's disease and found impair­
ments in both aspects of function. Hovestadt et al (26) found that visuo­
spatial disturbances occur in patients with Parkinson's disease in early
stages of the disorder and also in patients with unilateral involvement.
Visuospatial deficits are also prominent in DAT (15), but tentative
evidence suggests that the type of visuospatial disturbances exhibited by
cortical and subcortical disorders may differ. Brouwers et al (27) compared
DAT and Huntington's disease patients and found that the former had
greater difficulty with constructions whereas the latter were more compro­
mised on tests of map interpretation.

Language Changes
Language testing has proven to be among the most reliable means of
distinguishing subcortical and cortical dementias: linguistic functions are
relatively spared in the subcortical dementing disorders, whereas they
are prominently affected from the early stages of the cortical dementias.
Patients with Parkinson's disease perform normally on tests of naming
unless their dementia syndrome is severe (28-30). Maher et al (13) failed to
 SUBCORTICAL DEMENTIA 57
identify any language alterations in patients with progressive supranuclear
palsy, and Caine et al (31) found that language changes in Huntington's
disease were mild and relatively less profound than memory and abstrac­
tion alterations.
In contrast to the mild linguistic changes exhibited by patients with
subcortical dementias, DAT patients exhibit marked language abnor­
malities. They progress from anomie disturbances to transcortical sensory­
type aphasia with fluent verbal output, impaired comprehension, anomia,
aphasic agraphia, impaired reading comprehension and preservation of
the ability to repeat and to read aloud (32, 33). In studies in which patients
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

with subcortical dementia (e.g. Parkinson's disease) were compared with

equally demented DAT patients, the latter consistently exhibited more
marked linguistic deficits (28, 34).

Mood Disorders, Psychosis, and Personality Alterations

Depression is common in subcortical dementing disorders and uncommon
in DAT. Caine & Shoulson (35) found that approximately 50% of patients
with Huntington's disease exhibited significant affective disturbances
(major depressive episodes or dysthymic disorders), and similarly high
rates of depressive symptomatology have been found among patients with
progressive supranuclear palsy and Parkinson's disease (36, 37). In DAT,
depressive symptoms are uncommon: Cummings et al (38) found that 17%
of 30 DAT patients manifested depressive symptoms and none
had experienced a major depressive episode. Similarly, Knesevich and co­
workers (39) found no evidence of depression in a group of DAT
patients when first seen or when reexamined one year later.
Psychosis may be present in either subcortical or cortical dementias.
Psychosis is common in Huntington's disease and OAT (35, 38). Delusions
of persecution, infidelity, and theft occur in approximately 50% of DAT
patients during the course of their illness (38). Psychosis is uncommon
in untreated idiopathic Parkinson's disease or progressive supranuclear
palsy.
Personality alterations occur in both subcortical and cortical dementias
but the nature of the changes in demeanor are distinctively different.
Patients with progressive supranuclear palsy and Parkinson's disease exhi­
bit more inertia, indifference, disinterest, and deviance from social rules
than equally demented DAT patients (15), and Huntington's disease pati­
ents manifest apathy and irritability as well as an increased prevalence of
personality disorders (35). DAT patients tend to maintain a facade of
acceptable social behaviors despite intellectual deterioration and
emotional indifference, whereas patients with subcortical dementias dis­
play more abnormal and more socially inappropriate behavior (5).
 58 CUMMINGS & BENSON

NEUROCHEMICAL ALTERATIONS

The gross morphological and histopathologic alterations of the dementia

syndromes are relatively well known; recent investigations of these dis­
orders have focused on neurochemical changes. Dopamine deficiency
appears capable of producing a subcortical dementia syndrome. Dopamine
loss is the principal abnormality of idiopathic Parkinson's disease and
progressive supranuclear palsy and is the sole neurochemical deficiency
of MPTP-parkinsonism (40-42). Subcortical dementia is the principal
intellectual manifestation of these three disorders.
Gamma-aminobutyric acid (GABA) is depleted in Huntington's disease;
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

glutamate binding is markedly abnormal in subcortical basal ganglionic

structures (particularly the caudate nucleus) but normal in the cerebral
cortex of Huntington's disease patients (43). The opposite anatomic pat­
tern of glutamate binding is seen in DAT.
Acetylcholine is the primary neurotransmitter affected in DAT. Chol­
inergic systems are involved in some, but not all, patients with Parkinson's
disease and are unaffected in most other subcortical dementias (40, 41).

ELECTROPHYSIOLOGIC AND METABOLIC

ABNORMALITIES

Goodin & Aminoff (44) recently investigated electrophysiologic abnor­

malities in patients with Huntington's disease, Parkinson's disease, and
DAT. The two subcortical dementias exhibited similar abnormalities and
manifested significantly longer latencies of auditory evoked potentials (Nt,
P2, N2, P3) than did the dementias of the Alzheimer type. The longer
latencies were evident even though the severity of the intellectual deterior­
ation was less marked than that of the DAT patients.
Studies using positron emission tomography (PET) to map regional
glucose metabolism support the dicotomy between subcortical and cortical
type dementias. The most marked distinctions are found between Hun­
tington's disease and DAT. Decreased glucose metabolism is demonstrable
in the caudate nucleus in Huntington's disease even before structural
alterations are evident on X-ray computed tomograms and when
behavioral and motor symptoms are minimal. Cerebral cortical metab­
olism is unaffected (45, 46). PET scan studies in DAT reveal decreased
metabolism in parietal and frontal cortex with intact subcortical metab­
olism (47). PET scans in progressive supranuclear palsy demonstrate
diminished metabolic activity in the frontal lobes (48), and PET scans in
Parkinson's disease show a mild diffuse decrement in metabolism of both
cortical and subcortical structures (49).
 SUBCORTICAL DEMENTIA 59

COMMENT

Subcortical dementia is becoming increasingly well established as a useful

clinical and valid theoretical concept. Clinical, electrophysiologic, meta­
bolic, and biochemical studies support the concept of a dementia syndrome
based on dysfunction of subcortical structures and demonstrate that these
disorders share features that distinguish them from diseases affecting pri­
marily the cerebral cortex. Clinically, cortical dementias are untreatable,
whereas subcortical dementias frequently have treatable components. Cur­
rently, there is no effective therapy for DAT; awareness of the charac­
teristics of subcortical dementias allows the clinician to distinguish poten­
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.

tially treatable illnesses with subcortical dysfunction (Parkinson's disease,

multi-infarct dementia, subcortical neoplasms, infections, and inflam­
matory disorders) from DAT. Conceptually, observations of subcortical
dementia are enriching our appreciation of the role of the basal ganglia in
intellectual function.

ACKNOWLEDGMENT

This proj ect

was supported by the Veterans Administration and the John
Douglas French Foundation of Los Angeles. Bonita Porch prepared the
manuscript.

Literature Cited

1. Cummings, J. L., Benson, D. F., 8. Taylor, A E., Saint-Cyr., J. A., Lang,

LoVenne, S. Jr. 1980. Reversible de­
mentia. J. Am. Med. Assoc. 243: 2434-
39
2. Rogers, D. 1986. Bradyphrenia in par­
kinsonism: a historical review. Psychol.
Med. 16: 257---6 5
3. Evarts, E. V., Teravainen, R., Caine, D.
A. 1981. Reaction time in Parkinson's
disease. Brain 104: 167-86
4. Rogers, D. A, Lees, A J., Trimble ,
M., Stern, G. M. 1986. Concept of
bradyphrenia: a neuropsychiatric ap­
proach. Adv. Neural. 45: 447-50
5. Cummings, J. L., Benson, D. F. 1986.
Dementia of the Alzheimer type: an
inventory of diagnostic clinical features.
J. Am. Geriatr. Soc. 35: 394-97
6. Stuss, D., Benson, D. F. 1986. The Fron­
tal Lobes. New York: Raven
7. Flowers, K. A., Robertson, C. 1985. The
effect of Parkinson's disease on the
ability to maintain a mental set. J.
Neurol. Neurosurg. Psychiatry 48: 517-
29
A. E. 1986. Frontal lobe dysfunction in
Parkinson's disease. Brain 109: 845 83
9. Lees, A. J., Smith, E. 1983. Cognitive
deficits in the early stages of Parkinson's
disease. Brain 106: 257-60
10. Goldenberg, G., Wimmer, A., Auff, A.,
Schnaberth, G. 1986. Impainnent of
motor planning in patients with Par­
kinson's disease: evidence from ideo­
motor apraxia testing. J. Neural. Neuro­
surg. Psychiatry 49: 1266--72
II. Pirozzolo, F. J., Hansch, E. C., Morti­
mer, J. A, Webster, D. D., Kuskow­
ski, M. A. 1982. Dementia in Parkinson's
disease: a neuropsychological analy­
sis. Brain Cognit. I: 71-83
12. Sharpe, M. R., Cennak, S. A., Sax, D.
S. 1983. Motor planning in Parkinson
patients. Neuropsychologia 21: 455-62
13. Maher, E. R., Smith, E., Lees, A. J. 1985.
Cognitive deficits in Steel-Richardson­
Olszewski syndrome (progressive supra­
nuclear palsy). J. Neural. Neurosurg.
Psychiatry 48: 1234-39
 60 CUMMINGS & BENSON
14. Lasker, A. G., Zee, D. S., Hain, T. c.,
Folstein, S. E., Singer, H. S. 1987. Sac­
cades in Huntington's disease: initiation
defects and distractability. Neurology
37: 364--70
15. Pillon, B., Dubois, B., Lhermitte, F.,
Agid, Y. 1986. Heterogeneity of cog­
nitive impairment in progressive supran­
uclear palsy, Parkinson's disease, and
Alzheimer's disease. Neurology 36:
1179-85
16. Butters, N., Albert, M. S., Sax, D. S.,
Miliotis, P., Nagode, J., et al. 1983 . The
effect of verbal mediation on the pic­
torial memory of brain-damaged pati­
ents. Neuropsychologia 21: 307-23
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.
17. Martone, M., Butters, N., Trauner, D.
1986. Some analyses of forgetting of pic­
torial material in amnesic and demented
patients. J. Clin. Exp. Neuropsychol. 8:
161-78
18. Wilson, R. S., Como, P. G., Garron, D.
c., Klawans, H. L., Barr, A., et al. 1987.
Memory failure in Huntington's disease.
J. Clin. Exp. Neuropsychol. 9: 147-54
19 . Flowers, K. A., Pearce, I., Pearce, J. M.
S. 1984. Recognition memory in Par­
kinson's disease. J. Neurol. Neurosurg.
Psychialry47: 1174-81
20. Huber, S. J., Shuttleworth, E. C., Paul­
son, G. W, 1986. Dementia in Par­
kinson's disease. Arch. Neurol. 43: 987-
90
21. Weingartner, H., Burns, S., Diebel, R.,
LeWitt, P. A. 1984. Cognitive impair­
ments in Parkinson's disease: dis­
tinguishing between effort-demanding
and automatic cognitive processes. Psy­
chiatr. Res. II: 223-35
22. Davis, P. E., Mumford, S. J. 1984. Cued
recalJ and the nature of the memory dis­
order in dementia. Br. J. Psychiatry 144:
383-86
23. Kopelman, M. D. 1985. Rates of for­
getting in Alzheimer-type dementia and
Korsakoff's syndrome. Neuropsychol­
ogia 23: 623-28
24. Villardita, C., Smirni, P., Le Pira, F.,
Zappala, G., Nicoletti, F. 1982. Mental
deterioration, visuoperceptive disabil­
ities and constructional apraxia in Par­
kinson's disease. Acta Neurol. Scand. 66:
112-20
25. Boller, F., Passafiume, D., Keefe, N. c.,
Rogers, K., Morrow, L., et al. 1984.
Visuospatial impairment in Parkinson's
disease. Arch. Neurol. 41: 485-90
26. Hovestadt, A., de Jong, G. J., Meer­
waldt, J. D. 1987. Spatial disorientation
as an early symptom of Parkinson's dis­
ease. Neurology 37: 485-87
27. Brouwers, P., Cox, C., Martin, A.,
Chase, T., Fedio, P. 1984. Differential
perceptual-spatial impairment in Hun­
tington's and Alzheimer's dementias.
Arch. Neurol. 41: 1073-76
28. Bayles, K. A., Tomoeda, C. K. 1983.
Confrontation naming impairment in
dementia. Brain Lang. 19 : 98-114
29. Freedman, M., Rivoira, P., Buttcrs, N.,
Sax, D., Feldman. R. G. 1984. Retro­
grade amnesia in Parkinson's disease.
Can. J. Neurol. Sci. 1 1: 297-301
30. Huber, S. J., Shuttleworth, E. C., Paul­
son, G. W., Bellchambers, M. J. G.,
Clapp, L. E. 19 86. Cortical vs sub­
cortical dementia. Arch. Neurol. 43: 392-
94
3 1. Caine, E. D., Bamford, K. A., Schiffer,
R. B., Shoulson, I., Levy, S. 1986. A
controlJed neuropsychological com­
parison of Huntington's disease and
mUltiple sclerosis. Arch. neurol. 43: 249-
54
32. Cummings, J. L., Benson, D. F., HilJ,
M. A., Read, S. 1985. Aphasia in
dementia of the Alzheimer type. Neur ­
ology 35: 394-9 7
33. Cummings, J. L., Houlihan, J. P., Hill,
M. A. 1986. The pattern of reading
deterioration in dementia of the Alzh­
eimer type: observations and impli­
cations. Brain Lang. 29: 3 15-23
34. Mendez, M., Cummings, J. L., Darkins,
A. W., Hill, M. A., Benson, D. F. 1987.
Alzheimer's disease: comparison of
speech and language alterations. Neur­
ology 37(Suppl. 1): 227 (Abstr.)
35. Caine, E. D., Shoulson, I. 1983. Psy­
chiatric syndromes in Huntington's dis­
ease. Am. J. Psychiatry 140: 728-33
36. Janatz, A., Appel, A. R. 1984. Psy­
chiatric aspects of progressive supran­
uclear palsy. J. Nero. Ment. Dis. 172:
85-89
37. Santamaria, J., Valles, A. 1986. Par­
kinson's disease with depression: a poss­
ible subgroup of idiopathic parkin­
sonism. Neurology 36: 1130-33
38. Cummings, J. L., Miller, B. L., Hill, M.
A., Neshkes, R. 1987. Neuropsychiatric
aspects of multi-infarct dementia and
dementia of the Alzheimer type. Arch.
Neural. 44: 389 -93
39. Kncsevich, J. W., Martin, R. L., Berg,
L., Danziger, W. 1983. Preliminary
report on affective symptoms in the early
stages of senile dementia of the Alzh­
eimer type. Am. J. Psychiatry 140: 233-
35
40. Cummings, J. L. 1987. The dementias
of Parkinson's disease. Eur. Neurol. In
press
41. Kish, S. J., Chang, L. J., Mirchandani,
L., Shannak, K., Homykiewicz, O. 1985.
Progressive supranuclear palsy: relation-

ship between extrapyramidal dis­
turbances, dementia, and brain neur­
otransmitter markers. Ann. Neural. 18:
530-36
42. Stern, Y., Langston, W. J. 198 5. Intel­
lectual changes in patients with MPTP­
induced parkinsonism. Neurology 35:
1506-9
43. Greenamyre, J. T., Penny, J. B., Young,
A. B., D'Amato, C. D., Hicks, S. P.,
et al. 1983. Alterations in L-glutama te
binding in Alzheimer's and Hun­
tington's disease. Science 227: 1496-99
44. Goodin, D. S., Aminoff, M. J. 1986.
Electrophysiologic differences between
subtypes of dementia. Brain 109: 1103-
Annu. Rev. Med. 1988.39:53-61. Downloaded from www.annualreviews.org
by University of Alabama - Birmingham on 01/18/13. For personal use only.
13
45. Hayden, M. R., Martin, W. R. W.,
Stoessl, A. J., Clark, C., Hollenberg, S.,
et al. 1986. Positron emission tom­
ography in the early diagnosis of Hun­
tington's disease. Neurology 36: 888-94
46. Young, A. B., Penny, J. B., Starosta-
SUBCORTICAL DEMENTIA 61
Rubinstein, S., Markel, D. S., Berent, S.,
et al. 1986. PET scan investigations of
Huntington's disease: cerebral meta­
bolic correlates of neurological features
and functional decline. Ann. Neurol. 20:
296-303
47. Cutler, N. R., Harby, J. V., Duara, R.,
Grady, C. L., Kay, A, D., et al. 1985.
Clinical history, brain metabolism,
and neuropsychological function in Alz­
heimer's disease. Ann. Neurol. 18: 298-
309
48 . D'Antona, R., Baron, 1. C., Sam son,
Y., Serdari, M., Viader, F., et al. 1985.
Frontal cortex hypometabolism detec­
ted by positron emission tomography
in patients with progressive supranuc­
lear palsy. Brain 108: 785-89
49. Kuhl, D. E., Metter, E. J., Riege, W.
H. 1984. Patterns of local cerebral glu­
cose utilization determined in Parkin­
son's disease by 18F-fluorodeoxyglucose
method. Ann. Neurol. 15: 419-24