Second edition

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Lacunar dementia may also pursue a classic ‘stepwise’
course; however, several features serve to distinguish it
from multi-infarct dementia. First, one typically finds a
history of ‘lacunar syndromes’, such as pure motor stroke,
pure sensory stroke, etc. Second, as noted earlier, in lacunar
dementia, one may also find a progressive downhill
course in between the obvious strokes (Ishii et al. 1986;
Yoshitake et al. 1995). Third, and finally, lacunar dementia
is often marked clinically by a frontal lobe syndrome (Ishii
et al. 1986; Wolfe et al. 1990). Eventually, however, the diagnosis
is often made on MR scanning, which reveals multiple
subcortical lacunes.
Binswanger’s disease classically presents with a dementia
that pursues a gradual downhill course; this disease, however,
often is accompanied by small vessel disease and lacunar
strokes (Caplan and Schoene 1978; Kinkel et al. 1985;
Revesz et al. 1989) and is difficult to distinguish from lacunar
dementia on a clinical basis. MR scanning will reveal,
however, the leukoencephalopathy typical of Binswanger’s
disease, thus making the diagnosis.
Cranial arteritis may rarely cause a dementia, of either
the multi-infarct or lacunar type (Caselli 1990, Nightingale
et al. 1982). Diagnostic clues include unilateral headache
(generally temporal in location), amaurosis fugax, and
polymyalgia rheumatica.
Cerebral amyloid angiopathy classically presents with
a gradually progressive dementia punctuated by lobar
intracerebral hemorrhages (Cosgrove et al. 1985; Gilles et al.
1984), demonstrable on computed tomography (CT) or magnetic
resonance imaging (MRI) and suggested clinically by the
prominent headache associated with the lobar hemorrhage.
CADASIL presents in a fashion similar to that of
Binswanger’s disease. Distinguishing features include
migrainous headaches and a family history consistent with
an autosomal dominant inheritance (Dichgans et al. 1998;
Jung et al. 1995; Malandrini et al. 1996).
MELAS syndrome is a rare maternally inherited disorder
that, although generally presenting in the childhood years,
may present in adulthood with stroke-like episodes, progressive
dementia, migraine-like headaches, and hearing loss
(Clark et al. 1996).
CHARACTERIZED BY A FRONTAL LOBE SYNDROME
The frontal lobe syndrome, as discussed further in Section
7.2, is marked by varying degrees of affective changes
(euphoria or irritability), disinhibition and perseveration,
and its appearance early on in a dementing disorder is
strongly suggestive of frontal pathology, as may be seen
with various tumors and in certain neurodegenerative disorders,
such as Pick’s disease, frontotemporal dementia,
and amyotrophic lateral sclerosis.
Frontotemporal dementia, like Pick’s disease, typically
presents with a frontal lobe syndrome. A distinguishing
feature in some cases is the early appearance of an aphasic
disturbance of the motor or anomic type (Heutink et al.
1997; Mann et al. 1993; Neary et al. 1993).
5.1 Dementia 167
Pick’s disease classically presents with the frontal lobe
syndrome (Bouton 1940; Ferraro and Jervis 1936), and it is
indeed this presentation that most strongly distinguishes it
from Alzheimer’s disease (Litvan et al. 1997a; Mendez et al.
1993).
Amyotrophic lateral sclerosis, once thought to spare the
cortex outside the precentral gyrus, is now known to involve
the frontal lobes. In a minority, the disease may present with
a frontal lobe syndrome followed by a dementia and typical
upper and lower motor neuron signs (Cavalleri and De
Renzi 1994; Neary et al. 1990; Peavy et al. 1992).
Tumors of the frontal lobe may present with a dementia
marked by a frontal lobe syndrome (Avery 1971; Frazier
1936; Williamson 1896), which is true not only of tumors
confined to the frontal lobe, but also of those tumors of the
corpus callosum that extend laterally into the adjacent
frontal lobes (Moersch 1925).
WITH A PROGRESSIVE APHASIA
A number of different neurodegenerative diseases may
present with an isolated aphasia in a syndrome known as
‘primary progressive aphasia’. In such cases, the aphasia
progressively worsens and is eventually joined by a dementia.
Such a scenario has been noted in Alzheimer’s disease
(Green et al. 1990, 1996; Karbe et al. 1993), Pick’s disease
(Kertesz et al. 1994), and frontotemporal dementia (Neary
et al. 1993; Snowden et al. 1992; Turner et al. 1996); other,
much less common, causes include corticobasal ganglionic
degeneration (Ikeda et al. 1996), progressive supranuclear
palsy (Knibb et al. 2000), and Creutzfeldt–Jakob disease
(Mandell et al. 1989). It must be borne in mind that a similar
picture may occur with slowly growing appropriately
situated tumors.
WITH PARKINSONISM
The combination of dementia and parkinsonism may
occur secondary to a large number of disorders, of which
certain neurodegenerative disorders are the most common.
Of these neurodegenerative disorders, the most frequent
causes are Parkinson’s disease, diffuse Lewy body disease,
and multiple system atrophy, each one of which, in addition
to dementia, may cause a fairly ‘classic’ parkinsonism;
other neurodegenerative disorders to consider include
progressive supranuclear palsy, corticobasal ganglionic
degeneration, and frontotemporal dementia; however, as
detailed below, the parkinsonism seen in these disorders
tends to have some distinctive atypical features. Some
other disorders that present in a fashion similar to these
neurodegenerative ones include vascular parkinsonism,
dementia pugilistica, and Fahr’s syndrome.
Less common disorders to consider include those with
more or less obvious precipitating factors, such as intoxications
(carbon monoxide, manganese, methanol) and treatment
with valproic acid. Miscellaneous, and rare, causes
include hypoparathyroidism, pantothenate kinase-associated