10.1192/bjp.180.2.

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2002, 180:148-151. BJP
MARK A. TURNER, NICHOLAS F. MORAN and MICHAEL D. KOPELMAN
Subcortical dementia
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Background Background Drawinga distinction Drawinga distinction
betweencortical and subcortical betweencortical and subcortical
dementias seems bothuseful andjustified. dementias seems bothuseful andjustified.
Recent researchhas, however, cast doubt Recent researchhas, however, castdoubt
onthe clinical, neuropsychological, onthe clinical, neuropsychological,
neuroimagingandneuroanatomical basis neuroimagingandneuroanatomical basis
of the distinction. of the distinction.
Aims Aims To arrive at a reasonedconclusion To arrive at a reasonedconclusion
abouttherelationship betweenthetwo abouttherelationship betweenthetwo
types of dementia andthe validityof types of dementia andthe validityof
distinguishing betweenthem. distinguishing betweenthem.
Method Method The historical andrecent The historical andrecent
clinical and scientificliterature on clinical and scientificliterature on
subcortical dementia was reviewed. subcortical dementia was reviewed.
Results Results Thetraditional claimthat Thetraditional claimthat
subcortical dementia has distinctclinical subcortical dementia has distinct clinical
manifestations, neuroimaging findings and manifestations, neuroimaging findings and
a neuropathological profileis not a neuropathological profileis not
altogether borne out by theliterature. altogether borne out by theliterature.
Some studies show that frontal executive Some studies show that frontal executive
dysfunction andthe profile of memory dysfunction andthe profile of memory
deficits are not significantlydifferent from deficits are not significantlydifferent from
those seenin Alzheimer's disease. those seenin Alzheimer's disease.
Neuropathological findings also overlap. Neuropathological findings also overlap.
Conclusions Conclusions The categoryof The categoryof
subcortical dementia maybe clinically subcortical dementia maybe clinically
useful inhighlighting thelikelihoodthat an useful inhighlighting thelikelihoodthat an
individual with dementia is morelikely to individual with dementia is morelikely to
suffer frombradyphrenia andmotor suffer frombradyphrenia andmotor
difficulties. As neuroscience advances a difficulties. As neuroscience advances a
preoccupationwiththe distinctionmay preoccupationwiththe distinctionmay
hinder the assessment andtreatment of hinder the assessment andtreatment of
individual cases. individual cases.
Declaration of interest Declaration of interest None. None.
The concept of subcortical dementia devel- The concept of subcortical dementia devel-
oped out of clinical observations of de- oped out of clinical observations of de-
mentia in the context of disease processes mentia in the context of disease processes
preferentially affecting the subcortical preferentially affecting the subcortical
structures. The syndrome was claimed to structures. The syndrome was claimed to
be distinct in its clinical manifestations be distinct in its clinical manifestations
and its anatomicopathological correlates. and its anatomicopathological correlates.
The dichotomy between cortical and sub- The dichotomy between cortical and sub-
cortical dementias has now come under cortical dementias has now come under
attack from both the neuropsychological attack from both the neuropsychological
and neuroanatomical perspectives. and neuroanatomical perspectives.
BACKGROUND BACKGROUND
Dementia is a degenerative disorder invol- Dementia is a degenerative disorder invol-
ving the compromise of multiple domains ving the compromise of multiple domains
of cognition. This definition excludes acute of cognition. This definition excludes acute
confusion of any cause and also chronic confusion of any cause and also chronic
focal brain syndromes, in particular the focal brain syndromes, in particular the
amnesic syndrome. The further classifica- amnesic syndrome. The further classifica-
tion of dementia, whether based on clinical tion of dementia, whether based on clinical
presentation or on aetiology, is, however, presentation or on aetiology, is, however,
fraught with difficulties. Despite this, the fraught with difficulties. Despite this, the
emerging view since the mid-1970s has emerging view since the mid-1970s has
been that dementia can be separated into been that dementia can be separated into
cortical and subcortical types, a distinction cortical and subcortical types, a distinction
that has found support from both the clini- that has found support from both the clini-
cal (Pillon cal (Pillon et al et al, 1993, for example) and , 1993, for example) and
aetiological perspectives (see Darvesh & aetiological perspectives (see Darvesh &
Freedman, 1996, for a review). The differ- Freedman, 1996, for a review). The differ-
entiating features of subcortical dementia entiating features of subcortical dementia
were said to be a profound slowing of cog- were said to be a profound slowing of cog-
nition, memory disturbances, frontal execu- nition, memory disturbances, frontal execu-
tive dysfunction, and changes in personality tive dysfunction, and changes in personality
and affect in the absence of aphasias, and affect in the absence of aphasias,
apraxias and agnosias (Cummings, 1986). apraxias and agnosias (Cummings, 1986).
Other authors have highlighted the dif- Other authors have highlighted the dif-
ficulties with the distinction by arguing that ficulties with the distinction by arguing that
the neuropsychological profiles of cortical the neuropsychological profiles of cortical
and subcortical cases are not sufficiently and subcortical cases are not sufficiently
dissimilar (Brown & Marsden, 1988) or dissimilar (Brown & Marsden, 1988) or
that cortical abnormalities often occur in that cortical abnormalities often occur in
so-called subcortical disease (Hughes so-called subcortical disease (Hughes et al et al, ,
1993). With improvements in investigative 1993). With improvements in investigative
techniques, notably neuroimaging, the techniques, notably neuroimaging, the
debate about this matter is likely to continue. debate about this matter is likely to continue.
The evolution of the concept The evolution of the concept
In 1872, at a time when dementia was a In 1872, at a time when dementia was a
unitary concept, Huntington published unitary concept, Huntington published
`On Chorea', describing the cognitive `On Chorea', describing the cognitive
impairments in the disease that bears his impairments in the disease that bears his
name. In 1874 Meynert, whose interests name. In 1874 Meynert, whose interests
were both clinical and neuroanatomical, were both clinical and neuroanatomical,
published published Psychiatry: A Clinical Treatise Psychiatry: A Clinical Treatise
on Diseases of the Forebrain Based upon on Diseases of the Forebrain Based upon
its Structure, Function and its Nutrition its Structure, Function and its Nutrition. .
In this book he sought to relate brain struc- In this book he sought to relate brain struc-
ture to function, and postulated that certain ture to function, and postulated that certain
psychiatric symptoms resulted from an psychiatric symptoms resulted from an
imbalance of blood flow between the sub- imbalance of blood flow between the sub-
cortical and cortical structures. Meynert cortical and cortical structures. Meynert
may have been mistaken in making his may have been mistaken in making his
emphasis on blood flow, but if he had emphasis on blood flow, but if he had
talked in neural terms instead, he would talked in neural terms instead, he would
surely have pre-empted current thinking surely have pre-empted current thinking
about the aetiology of subcortical demen- about the aetiology of subcortical demen-
tia. In 1894 Binswanger introduced a tia. In 1894 Binswanger introduced a
vascular perspective and characterised vascular perspective and characterised
encephalitis subcorticalis chronica pro- encephalitis subcorticalis chronica pro-
gressiva gressiva, subsequently renamed subcortical , subsequently renamed subcortical
arteriosclerotic encephalopathy by Olszewski arteriosclerotic encephalopathy by Olszewski
in 1962. in 1962.
In 1912 Wilson related subcortical In 1912 Wilson related subcortical
disease to a clinical picture distinct from disease to a clinical picture distinct from
that seen in cortical dementia when he that seen in cortical dementia when he
described cognitive impairments in the described cognitive impairments in the
absence of apraxia and agnosia in cases of absence of apraxia and agnosia in cases of
`progressive lenticular degeneration: a `progressive lenticular degeneration: a
familial nervous disease associated with familial nervous disease associated with
cirrhosis of the liver', commonly known cirrhosis of the liver', commonly known
nowadays as Wilson's disease. Sub- nowadays as Wilson's disease. Sub-
sequently a number of other predominantly sequently a number of other predominantly
subcortical disease processes have been subcortical disease processes have been
characterised and found to be associated characterised and found to be associated
with a pattern of cognitive impairment that with a pattern of cognitive impairment that
supports the idea of distinction between supports the idea of distinction between
cortical and subcortical dementias. Parkin- cortical and subcortical dementias. Parkin-
son's disease was not formally incorporated son's disease was not formally incorporated
into the notion of subcortical dementia into the notion of subcortical dementia
until 1978, following work by Albert, until 1978, following work by Albert,
although debate about its aetiology and its although debate about its aetiology and its
relationship with cognitive impairment relationship with cognitive impairment
started as far back as 1932 when Von started as far back as 1932 when Von
Stockert introduced the term Stockert introduced the term subcorticale subcorticale
demenz demenz to characterise the cognitive to characterise the cognitive
impairment evident in a case of encephalitis impairment evident in a case of encephalitis
lethargica. Concerning more obscure lethargica. Concerning more obscure
causes, in 1938 Smyth and Stern had causes, in 1938 Smyth and Stern had
described cognitive impairment in the pre- described cognitive impairment in the pre-
sence of thalamic disease. More recently, sence of thalamic disease. More recently,
in 1974 Segarra and co-workers supported in 1974 Segarra and co-workers supported
the contention that subcortical dementia the contention that subcortical dementia
can occur in the presence of isolated thala- can occur in the presence of isolated thala-
mic disease, and in 1984 Katz also specu- mic disease, and in 1984 Katz also specu-
lated that the dementia associated with lated that the dementia associated with
14 8 14 8
BRI TI S H J OURNAL OF P SYCHI ATRY BRI TI S H J OURNAL OF P SYCHI ATRY ( 2 0 0 2 ) , 1 8 0 , 14 8 ^ 1 51 ( 2 0 0 2 ) , 1 8 0 , 1 4 8 ^ 1 51
Subcortical dementia Subcortical dementia
{ {
MARK A. TURNER, NICHOLAS F. MORAN and MICHAEL D. KOPELMAN MARK A. TURNER, NICHOLAS F. MORAN and MICHAEL D. KOPELMAN
y
See editorial, pp. 97^98, this issue. See editorial, pp. 97^98, this issue.
SUBCORTI CAL DEMENTI A SUBCORTI CAL DEMENTI A
multi-system atrophy may be of thalamic multi-system atrophy may be of thalamic
origin. origin.
Although McHugh apparently used the Although McHugh apparently used the
term `subcortical dementia' to characterise term `subcortical dementia' to characterise
the deficits seen in Huntington's disease in the deficits seen in Huntington's disease in
an unpublished communication in 1973, it an unpublished communication in 1973, it
was Albert and colleagues in 1974 who was Albert and colleagues in 1974 who
formally articulated the concept: in a dis- formally articulated the concept: in a dis-
cussion of the cognitive impairments associ- cussion of the cognitive impairments associ-
ated with progressive supranuclear palsy, ated with progressive supranuclear palsy,
Albert Albert et al et al (1974) specified the clinical (1974) specified the clinical
features of the syndrome for the first time. features of the syndrome for the first time.
Subsequently, a similar clinical picture Subsequently, a similar clinical picture
was described in association with basal was described in association with basal
ganglionic calcification in hyperpara- ganglionic calcification in hyperpara-
thyroidism by Bachman & Albert (1984) thyroidism by Bachman & Albert (1984)
and in human immunodeficiency virus and in human immunodeficiency virus
dementia by Navia dementia by Navia et al et al (1986). There are (1986). There are
a number of other neurological disorders, a number of other neurological disorders,
including normal pressure hydrocephalus, including normal pressure hydrocephalus,
the `pugilistic encephalopathy' of repeated the `pugilistic encephalopathy' of repeated
head injury, multiple sclerosis and the head injury, multiple sclerosis and the
spinocerebellar degenerations, that can be spinocerebellar degenerations, that can be
postulated as subcortical dementias but postulated as subcortical dementias but
are not mentioned again here. From the are not mentioned again here. From the
psychiatric perspective, there are similari- psychiatric perspective, there are similari-
ties between the clinical features of sub- ties between the clinical features of sub-
cortical dementia and those of depressive cortical dementia and those of depressive
pseudodementia (Caine, 1981) and type II pseudodementia (Caine, 1981) and type II
schizophrenia (Pantelis schizophrenia (Pantelis et al et al, 1992). , 1992).
CLINICAL AND CLINICAL AND
NEUROPSYCHOLOGICAL NEUROPSYCHOLOGICAL
MANIFESTATIONS MANIFESTATIONS
In Alzheimer's disease senile plaques and In Alzheimer's disease senile plaques and
neurofibrillary tangles populate the cortex neurofibrillary tangles populate the cortex
and there is generalised cortical atrophy, and there is generalised cortical atrophy,
especially of the frontal and temporal lobes, especially of the frontal and temporal lobes,
with neuronal degeneration affecting par- with neuronal degeneration affecting par-
ticularly the outer three layers. The typical ticularly the outer three layers. The typical
clinical findings include dyscalculia, dys- clinical findings include dyscalculia, dys-
phasias, dyspraxias and agnosias, and are phasias, dyspraxias and agnosias, and are
said to be indicative of cortical dysfunction. said to be indicative of cortical dysfunction.
However, features reflecting subcortical However, features reflecting subcortical
pathology, such as mild extrapyramidal pathology, such as mild extrapyramidal
signs, are common. signs, are common.
In the subcortical dementias, on the In the subcortical dementias, on the
other hand, the lesions occur pre- other hand, the lesions occur pre-
dominantly in the basal ganglia, the brain- dominantly in the basal ganglia, the brain-
stem nuclei and the cerebellum (see stem nuclei and the cerebellum (see
Darvesh & Freedman, 1996, for a compre- Darvesh & Freedman, 1996, for a compre-
hensive review of the neuroanatomy and hensive review of the neuroanatomy and
neuropathology), and the clinical picture neuropathology), and the clinical picture
is correspondingly different. In addition to is correspondingly different. In addition to
the clinical features of the underlying the clinical features of the underlying
disease process (whether it be Parkinson's, disease process (whether it be Parkinson's,
Huntington's or other disease) psychiatric Huntington's or other disease) psychiatric
disturbance, bradyphrenia, frontal executive disturbance, bradyphrenia, frontal executive
dysfunction and impairment in memory dysfunction and impairment in memory
characteristic of subcortical dementia may characteristic of subcortical dementia may
be present. be present.
The psychiatric manifestations of sub- The psychiatric manifestations of sub-
cortical disease come primarily in the form cortical disease come primarily in the form
of personality changes and affective dis- of personality changes and affective dis-
order. Apathy and irritability are particu- order. Apathy and irritability are particu-
larly common (Aarsland larly common (Aarsland et al et al, 1999), and , 1999), and
depression is said to be significantly more depression is said to be significantly more
common in subcortical disorders such as common in subcortical disorders such as
Parkinson's disease than it is in Alzheimer's Parkinson's disease than it is in Alzheimer's
disease. Aarsland disease. Aarsland et al et al (1999) found that (1999) found that
38% of a series of patients with Parkinson's 38% of a series of patients with Parkinson's
disease had depression, and Cummings disease had depression, and Cummings
(1995) gave a figure of 30% for Hunting- (1995) gave a figure of 30% for Hunting-
ton's disease that is broadly in keeping with ton's disease that is broadly in keeping with
the figure of 41% reported by Dewhurst the figure of 41% reported by Dewhurst
et al et al (1969) for their series of Huntington's (1969) for their series of Huntington's
cases. Psychotic illness and mania are also cases. Psychotic illness and mania are also
overrepresented, particularly in Hunting- overrepresented, particularly in Hunting-
ton's disease: psychotic illness was present ton's disease: psychotic illness was present
in over 50% and mania in 21% of the in over 50% and mania in 21% of the
Dewhurst series, and in the Parkinson's Dewhurst series, and in the Parkinson's
disease series 27% had hallucinations disease series 27% had hallucinations
(Aarsland (Aarsland et al et al, 1999). , 1999).
In terms of cognition, some evidence In terms of cognition, some evidence
suggests that cortical dementia evolves suggests that cortical dementia evolves
differently from subcortical dementia. Stern differently from subcortical dementia. Stern
et al et al (1998) evaluated cognitive changes (1998) evaluated cognitive changes
over 13 years prior to the time dementia over 13 years prior to the time dementia
was diagnosed in 40 matched pairs of was diagnosed in 40 matched pairs of
patients with Alzheimer's disease and patients with Alzheimer's disease and
Parkinson's disease. The study showed that Parkinson's disease. The study showed that
the decline in naming on the Boston the decline in naming on the Boston
Naming Test (Kaplan Naming Test (Kaplan et al et al, 1983) and in , 1983) and in
performance on the Selective Reminding performance on the Selective Reminding
Test (Buschke & Fuld, 1974) was more Test (Buschke & Fuld, 1974) was more
rapid in Parkinson's disease than in rapid in Parkinson's disease than in
Alzheimer's disease, which Stern and Alzheimer's disease, which Stern and
colleagues felt was in keeping with different colleagues felt was in keeping with different
underlying pathological processes. underlying pathological processes.
In terms of the actual pattern of deficits, In terms of the actual pattern of deficits,
slow thinking (bradyphrenia) has been slow thinking (bradyphrenia) has been
demonstrated in both Parkinson's disease demonstrated in both Parkinson's disease
and Huntington's disease and is indepen- and Huntington's disease and is indepen-
dent of attendant motor slowness. Frontal/ dent of attendant motor slowness. Frontal/
executive function, as evidenced by difficul- executive function, as evidenced by difficul-
ties with verbal fluency, set shifting, cate- ties with verbal fluency, set shifting, cate-
gorisation and planning, is also disturbed gorisation and planning, is also disturbed
in all the major subcortical diseases (Elias in all the major subcortical diseases (Elias
& Treland, 1999). It is also impaired in & Treland, 1999). It is also impaired in
early Alzheimer's dementia (Kopelman, early Alzheimer's dementia (Kopelman,
1991). There is evidence to suggest that 1991). There is evidence to suggest that
patients with early Alzheimer's disease are patients with early Alzheimer's disease are
disproportionately impaired in category disproportionately impaired in category
fluency as compared with letter fluency, a fluency as compared with letter fluency, a
fact that comfortably fits with more severe fact that comfortably fits with more severe
semantic memory problems in the former. semantic memory problems in the former.
In subcortical dementia (e.g. in Parkin- In subcortical dementia (e.g. in Parkin-
son's disease and Huntington's dementia), son's disease and Huntington's dementia),
there is a learning impairment which can there is a learning impairment which can
be partially corrected by providing richer be partially corrected by providing richer
(more salient) cues to encourage learning (more salient) cues to encourage learning
and promote recognition (Pillon and promote recognition (Pillon et al et al, ,
1993). In contrast, it was claimed that 1993). In contrast, it was claimed that
cortical dementias (such as Alzheimer's cortical dementias (such as Alzheimer's
dementia) are characterised by accelerated dementia) are characterised by accelerated
forgetting (e.g. Cummings, 1986). forgetting (e.g. Cummings, 1986).
However, this distinction does not hold However, this distinction does not hold
good on detailed neuropsychological good on detailed neuropsychological
analysis of the patterns of learning and analysis of the patterns of learning and
forgetting in, for example, Huntington's forgetting in, for example, Huntington's
disease and Alzheimer's dementia disease and Alzheimer's dementia
(Kopelman, 1985), and Kuzis (Kopelman, 1985), and Kuzis et al et al (1999) (1999)
could not demonstrate a different profile could not demonstrate a different profile
of memory deficits between patients with of memory deficits between patients with
Alzheimer's dementia and those with Alzheimer's dementia and those with
dementia consequent upon Parkinson's dementia consequent upon Parkinson's
disease. In remote memory, there are disease. In remote memory, there are
variable patterns of impairment. In Alz- variable patterns of impairment. In Alz-
heimer's dementia a gentle `temporal heimer's dementia a gentle `temporal
gradient' (an extensive remote memory loss gradient' (an extensive remote memory loss
with some degree or relative sparing of with some degree or relative sparing of
early memories) is found in many studies early memories) is found in many studies
(Kopelman, 1989), although there have (Kopelman, 1989), although there have
been claims that this is specific for auto- been claims that this is specific for auto-
biographical memories as opposed to biographical memories as opposed to
memories of famous events (Dorrego memories of famous events (Dorrego et al et al, ,
1999), whereas in Huntington's disease 1999), whereas in Huntington's disease
there is a `flat', uniform loss of remote there is a `flat', uniform loss of remote
memories across all earlier periods. In memories across all earlier periods. In
Parkinson's disease, the severity of remote Parkinson's disease, the severity of remote
memory impairment is related to the memory impairment is related to the
clinical severity of dementia; however, clinical severity of dementia; however,
these patients additionally seem to have these patients additionally seem to have
difficulty in dating past events, even when difficulty in dating past events, even when
they do not suffer from formal dementia. they do not suffer from formal dementia.
There have been many studies of There have been many studies of
procedural (perceptuomotor) learning in procedural (perceptuomotor) learning in
Parkinson's disease and Huntington's Parkinson's disease and Huntington's
dementia. Saint-Cyr dementia. Saint-Cyr et al et al (1988) found that (1988) found that
in both conditions patients were impaired in both conditions patients were impaired
at the Tower of Hanoi task, whereas at the Tower of Hanoi task, whereas
amnesic patients performed normally (on amnesic patients performed normally (on
the basis of the latter's intact procedural the basis of the latter's intact procedural
memory); on verbal memory tasks, in memory); on verbal memory tasks, in
contrast, the amnesic patients were severely contrast, the amnesic patients were severely
impaired, whereas those with Parkinson's impaired, whereas those with Parkinson's
disease performed normally and those with disease performed normally and those with
Huntington's disease showed a variable Huntington's disease showed a variable
pattern. More recently, Reber & Squire pattern. More recently, Reber & Squire
(1999) have demonstrated that skill (1999) have demonstrated that skill
learning is not a single entity: patients with learning is not a single entity: patients with
Parkinson's are impaired at `habit' learning, Parkinson's are impaired at `habit' learning,
implicating the neostriatum, but show implicating the neostriatum, but show
intact learning of artificial grammars and intact learning of artificial grammars and
dot pattern prototypes, which were dot pattern prototypes, which were
postulated to reflect brain regions outside postulated to reflect brain regions outside
both the neostriatum and the medial both the neostriatum and the medial
temporal lobes. temporal lobes.
14 9 14 9
TURNER ET AL TURNER E T AL
SUBCORTICAL SUBCORTICAL
CONTRIBUTIONTO CONTRIBUTIONTO
PSYCHIATRIC DISORDER? PSYCHIATRIC DISORDER?
For the purposes of investigating cognitive For the purposes of investigating cognitive
impairments in depression, Caine (1981) impairments in depression, Caine (1981)
defined `pseudodementia' as follows: defined `pseudodementia' as follows:
(a) (a) it is an intellectual impairment in a it is an intellectual impairment in a
patient with a primary psychiatric patient with a primary psychiatric
disorder; disorder;
(b) (b) the features of the neuropsychological the features of the neuropsychological
disorder resemble, at least in part, the disorder resemble, at least in part, the
presentation of a neuropathologically presentation of a neuropathologically
induced cognitive deficit; induced cognitive deficit;
(c) (c) the intellectual disorder is reversible; the intellectual disorder is reversible;
(d) (d) the patient has no apparent primary the patient has no apparent primary
neuropathological process leading to neuropathological process leading to
the genesis of the disturbance. the genesis of the disturbance.
The disorder in question is usually The disorder in question is usually
hysteria or depression but, because of the hysteria or depression but, because of the
additional complexities of understanding additional complexities of understanding
the mechanism of the former and how it the mechanism of the former and how it
relates to the purposeful behaviour of relates to the purposeful behaviour of
malingering, attention is here confined to malingering, attention is here confined to
depressive pseudodementia. depressive pseudodementia.
Depression is common in subcortical Depression is common in subcortical
disorders and it is perhaps not surprising disorders and it is perhaps not surprising
therefore that the pattern of cognitive therefore that the pattern of cognitive
impairment that one sees in the context of impairment that one sees in the context of
depression can be `subcortical'. As Lishman depression can be `subcortical'. As Lishman
(1987: p. 410) eloquently puts it: (1987: p. 410) eloquently puts it:
The patient becomes slow to grasp essentials, The patient becomes slow to grasp essentials,
thinking is laboured, and behaviour becomes thinking is laboured, and behaviour becomes
generally slipshod and inefficient. Events fail to generally slipshod and inefficient. Events fail to
register either through lack of ability to attend register either through lack of ability to attend
and concentrate or on account of the patient's and concentrate or on account of the patient's
inner preoccupations. In consequence he may inner preoccupations. In consequence he may
show faulty orientation, impairment of recent show faulty orientation, impairment of recent
memory, and a markedly defective knowledge memory, and a markedly defective knowledge
of current events. The impression of dementia is of current events. The impression of dementia is
sometimes strengthened by the patient's sometimes strengthened by the patient's
decrepit appearance due to self-neglect or loss decrepit appearance due to self-neglect or loss
of weight. of weight.
To clarify the nature of the transient To clarify the nature of the transient
cognitive impairments associated with cognitive impairments associated with
psychiatric disorder, Caine performed psychiatric disorder, Caine performed
neuropsychological testing on a series of neuropsychological testing on a series of
patients with pseudodementia and depres- patients with pseudodementia and depres-
sion. The results indicated a sparing of sion. The results indicated a sparing of
`cortically mediated intellectual functions' `cortically mediated intellectual functions'
(Caine, 1981: p. 1363), including language (Caine, 1981: p. 1363), including language
functions and motor praxis, but difficulties functions and motor praxis, but difficulties
with inattention, slow mental processing with inattention, slow mental processing
and a verbal elaboration `demonstrating a and a verbal elaboration `demonstrating a
subcortical pattern of intellectual deficit' subcortical pattern of intellectual deficit'
(Caine, 1981: p. 1364). In keeping with this (Caine, 1981: p. 1364). In keeping with this
line of argument, Rogers line of argument, Rogers et al et al (1987) sub- (1987) sub-
sequently drew attention to the similarities sequently drew attention to the similarities
between the cognitive slowness of Parkin- between the cognitive slowness of Parkin-
son's disease and that seen in depression, son's disease and that seen in depression,
thereby raising the interesting question of thereby raising the interesting question of
whether or not depression and the sub- whether or not depression and the sub-
cortical dementias share a common or cortical dementias share a common or
closely related aetiology. There is support closely related aetiology. There is support
for this hypothesis from both the neuro- for this hypothesis from both the neuro-
pathological and the functional imaging pathological and the functional imaging
perspectives. In patients with Parkinson's perspectives. In patients with Parkinson's
disease who had both depression and disease who had both depression and
dementia, Ring dementia, Ring et al et al (1994), for example, (1994), for example,
found hypometabolism in the medial pre- found hypometabolism in the medial pre-
frontal cortex using positron emission frontal cortex using positron emission
tomography (PET), suggesting that tomography (PET), suggesting that
frontal/subcortical changes may contribute frontal/subcortical changes may contribute
to (or reflect) depressed mood in this to (or reflect) depressed mood in this
disorder. disorder.
In type II schizophrenia, Pantelis In type II schizophrenia, Pantelis et al et al
(1992) addressed the question of whether (1992) addressed the question of whether
the features that are similar to those seen the features that are similar to those seen
in subcortical dementia (such as apathy in subcortical dementia (such as apathy
and lack of motivation) should be taken and lack of motivation) should be taken
as evidence of a subcortical aetiology. In as evidence of a subcortical aetiology. In
support of this, there is some neuropsycho- support of this, there is some neuropsycho-
logical and neuropathological evidence. In logical and neuropathological evidence. In
terms of neuropsychology, Nelson terms of neuropsychology, Nelson et al et al
(1990), for example, showed a significant (1990), for example, showed a significant
negative correlation between cognitive negative correlation between cognitive
speed and negative symptoms in patients speed and negative symptoms in patients
with schizophrenia. The neuropathological with schizophrenia. The neuropathological
evidence is less convincing, in spite of the evidence is less convincing, in spite of the
fact that a number of studies have revealed fact that a number of studies have revealed
subcortical structural abnormalities in subcortical structural abnormalities in
schizophrenia. Recent work suggests that schizophrenia. Recent work suggests that
the loss of tissue is more general and that the loss of tissue is more general and that
it may preferentially affect the cortex. The it may preferentially affect the cortex. The
tentative conclusion is therefore that, while tentative conclusion is therefore that, while
subcortical structures are likely to be subcortical structures are likely to be
affected in schizophrenia and may be affected in schizophrenia and may be
responsible for some of the clinical features responsible for some of the clinical features
of the disorder, other regions of the brain of the disorder, other regions of the brain
are also affected. are also affected.
THE LEGITIMACY THE LEGITIMACY
OF THE DISTINCTION OF THE DISTINCTION
It is well-recognised that cortical abnormal- It is well-recognised that cortical abnormal-
ities are frequently found in `subcortical' ities are frequently found in `subcortical'
diseases and vice versa. Hughes diseases and vice versa. Hughes et al et al
(1993) looked at 100 cases of histologically (1993) looked at 100 cases of histologically
confirmed Parkinson's disease and found confirmed Parkinson's disease and found
that in 17 there was coexistent neuropatho- that in 17 there was coexistent neuropatho-
logical evidence of Alzheimer-type change. logical evidence of Alzheimer-type change.
In fact, dementia had occurred in 44% of In fact, dementia had occurred in 44% of
these patients and of these 29% had these patients and of these 29% had
confirmed Alzheimer pathological change. confirmed Alzheimer pathological change.
Cortical change has also been documented Cortical change has also been documented
in Huntington's disease and progressive in Huntington's disease and progressive
supranuclear palsy. In Alzheimer's disease, supranuclear palsy. In Alzheimer's disease,
Whitehouse Whitehouse et al et al (1981) demonstrated loss (1981) demonstrated loss
of cholinergic neurons in the `subcortical' of cholinergic neurons in the `subcortical'
nucleus basalis of Meynert, a finding nucleus basalis of Meynert, a finding
corroborated by many others. corroborated by many others.
Neuroimaging findings in some studies Neuroimaging findings in some studies
add further weight to the idea that the add further weight to the idea that the
dichotomy is not strict. Starkstein dichotomy is not strict. Starkstein et al et al
(1997), for example, compared patients (1997), for example, compared patients
with Alzheimer's and Parkinson's disease with Alzheimer's and Parkinson's disease
with dementia with patients with Parkin- with dementia with patients with Parkin-
son's disease without dementia, using son's disease without dementia, using
single-photon emission computed tomo- single-photon emission computed tomo-
graphy (SPECT). They found that the two graphy (SPECT). They found that the two
groups with dementia did not differ signifi- groups with dementia did not differ signifi-
cantly from each other, but showed signifi- cantly from each other, but showed signifi-
cantly more severe hypoperfusion in the cantly more severe hypoperfusion in the
superior frontal, superior temporal and superior frontal, superior temporal and
parietal areas than did those without parietal areas than did those without
dementia. As a consequence, any classifica- dementia. As a consequence, any classifica-
tion of the dementias must be sensitive to tion of the dementias must be sensitive to
the fact that they seem to lie along a con- the fact that they seem to lie along a con-
tinuum involving a greater or lesser degree tinuum involving a greater or lesser degree
of cortical and subcortical pathology. of cortical and subcortical pathology.
Even if one accepts the notion of a Even if one accepts the notion of a
continuum, this still leaves a number of continuum, this still leaves a number of
unresolved issues. It is difficult to sustain unresolved issues. It is difficult to sustain
the idea that cortical dementia alone is the idea that cortical dementia alone is
characterised by some combination of characterised by some combination of
aphasia, apraxia and agnosia, since apraxia aphasia, apraxia and agnosia, since apraxia
is known to occur in disorders affecting the is known to occur in disorders affecting the
basal ganglia. In addition, a number of basal ganglia. In addition, a number of
published care reports indicate that published care reports indicate that
thalamic lesions sometimes produce demen- thalamic lesions sometimes produce demen-
tia indistinguishable from Alzheimer's tia indistinguishable from Alzheimer's
disease, and that frontal dysfunction said disease, and that frontal dysfunction said
to be one of the characteristic features of to be one of the characteristic features of
subcortical dementia is common in early subcortical dementia is common in early
Alzheimer's disease (Kopelman, 1991). Alzheimer's disease (Kopelman, 1991).
In conclusion, there is no specific In conclusion, there is no specific
neuropsychological pattern in subcortical neuropsychological pattern in subcortical
dementia. However, the subcortical dis- dementia. However, the subcortical dis-
orders may still be more similar to one orders may still be more similar to one
another than they are to Alzheimer's another than they are to Alzheimer's
dementia. In so far as this is the case, they dementia. In so far as this is the case, they
are characterised by cognitive slowness, are characterised by cognitive slowness,
concomitant motor abnormalities, and a concomitant motor abnormalities, and a
relatively low frequency of aphasias and relatively low frequency of aphasias and
apraxias. When the latter occur, they reflect apraxias. When the latter occur, they reflect
damage to subcorticalcortical projections. damage to subcorticalcortical projections.
However, modern neuropsychology focuses However, modern neuropsychology focuses
its attention on specific patterns of cog- its attention on specific patterns of cog-
nitive impairment in relation to underlying nitive impairment in relation to underlying
neurochemistry or neuropathology: to this neurochemistry or neuropathology: to this
extent, concepts such as `subcortical extent, concepts such as `subcortical
dementia' are likely to blur, rather than to dementia' are likely to blur, rather than to
illuminate, our understanding. illuminate, our understanding.
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151 151
CLINICAL IMPLICATIONS CLINICAL IMPLICATIONS
& &
Psychiatric illness, including psychosis, is relatively common in patients with Psychiatric illness, including psychosis, is relatively common in patients with
subcortical disease and is a major cause of morbidity. subcortical disease and is a major cause of morbidity.
& & Clinical, neuropsychological and neuropathological findings do not allow the strict Clinical, neuropsychological and neuropathological findings do not allow the strict
separation of the dementias into subcortical and cortical subgroups. separation of the dementias into subcortical and cortical subgroups.
& &
Less emphasis should be placed on the issue of whether or not clinical and Less emphasis should be placed on the issue of whether or not clinical and
neuropsychological findings fit typical cortical or subcortical pictures and neuropsychological findings fit typical cortical or subcortical pictures and
assessments should be directed towards identifying the precise cause of a dementia assessments should be directed towards identifying the precise cause of a dementia
and appraising functional deficits that have implications for management. and appraising functional deficits that have implications for management.
LIMITATIONS LIMITATIONS
& &
This paper is a brief review with a limitednumber of references and soby necessity This paper is a brief review with a limitednumber of references and soby necessity
a considerable amount of interesting neuropsychological material has had to be a considerable amount of interesting neuropsychological material has had to be
excluded. excluded.
& & The clinical differentiation between subcortical and cortical dementias using The clinical differentiation between subcortical and cortical dementias using
standardised instruments is not discussed. standardised instruments is not discussed.
& & Neuroimaging and neurochemical work are increasingly important in Neuroimaging and neurochemical work are increasingly important in
understanding the pathological basis of neuropsychological deficits and a more understanding the pathological basis of neuropsychological deficits and a more
comprehensive discussion of these matters would have been useful. comprehensive discussion of these matters would have been useful.
MARK A. TURNER, MRCPsych, Duchess of Kent Psychiatric Hospital, Catterick Garrison, NorthYorkshire; MARK A. TURNER, MRCPsych, Duchess of Kent Psychiatric Hospital, Catterick Garrison, NorthYorkshire;
NICHOLAS F. MORAN, MRCP, MICHAEL D. KOPELMAN, FRCPsych, St Thomas' Hospital, London, UK NICHOLAS F. MORAN, MRCP, MICHAEL D. KOPELMAN, FRCPsych, St Thomas' Hospital, London, UK
Correspondence: Dr MarkTurner, Duchess of Kent Psychiatric Hospital, Horne Road, Catterick Correspondence: Dr MarkTurner, Duchess of Kent Psychiatric Hospital, Horne Road, Catterick
Garrison, NorthYorkshire DL9 4DF,UK Garrison, NorthYorkshire DL9 4DF,UK
(First received 20 April 2000, final revision 8 May 2001, accepted 23 May 2001) (First received 20 April 2000, final revision 8 May 2001, accepted 23 May 2001)