Second edition

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168 Syndromes of cognitive impairment
neurodegeneration, juvenile-onset Huntington’s disease, and
systemic lupus erythematosus.
Parkinson’s disease may cause dementia but this is a late
development, generally not appearing until five or more
years after the parkinsonism has been well established. The
prevalence of dementia in patients with Parkinson’s disease
increases with age (Biggins et al. 1992; Marder et al. 1995)
and overall, in population-based studies, the prevalence of
dementia ranges from 18 percent (Tison et al. 1995) to 41
percent (Mayeux et al. 1992).
Diffuse Lewy body disease may present with parkinsonism;
however, within a year of the onset of the parkinsonism,
patients develop a dementia, and it is this ‘one year
rule’ that most reliably distinguishes diffuse Lewy body
disease from Parkinson’s disease. Other, helpful differential
features include the presence of hallucinations and
spontaneous episodes of confusion in the dementia of diffuse
Lewy body disease, features that are generally not as
prominent in Parkinson’s disease (Burkhardt et al. 1988;
Klatka et al. 1996; McKeith et al. 1994).
Multiple system atrophy of the striatonigral degeneration
type presents with a typical parkinsonism but it is generally
accompanied by evidence of either autonomic failure or
cerebellar involvement (Colosimo et al. 1995; Litvan et al.
1997b; Wenning et al. 1994, 1995). The autonomic failure
may include postural hypotension and dizziness, urinary
incontinence or retention, fecal incontinence, and erectile
dysfunction; cerebellar signs include ataxia and intention
tremor. A minority of these patient will eventually develop
a dementia (Robbins et al. 1992).
Progressive supranuclear palsy typically presents with
postural instability and frequent unexplained falls; over time,
parkinsonism develops, marked by rigidity, bradykinesia,
and, notably, a dystonic axial extension, which may also be
evident in the neck (Collins et al. 1995; Daniel et al. 1995;
Litvan et al. 1996a,b,c, 1997c). Most, but not all, patients
eventually demonstrate the hallmark of this disease, namely
supranuclear ophthalmoplegia for vertical gaze. Most
patients also eventually become demented and many will
also develop a pseudobulbar palsy with emotional incontinence
(Menza et al. 1995).
Corticobasal ganglionic degeneration typically presents
with a strikingly asymmetric rigid–akinetic parkinsonism,
generally in an arm, which may be accompanied by a dystonic
rigidity. Apraxia is a common accompaniment, and
some patients may also develop myoclonus (Litvan et al.
1997d; Riley et al. 1990; Rinne et al. 1994). A minority may
eventually become demented. Uncommonly, the disease
may present with dementia (Grimes et al. 1999), and in
such cases, parkinsonism may appear later (Schneider et al.
1997).
Frontotemporal dementia, specifically frontotemporal
dementia with parkinsonism linked to chromosome 17
(FTDP-17) (Pickering-Brown et al. 2002) typically presents
with a dementia marked by a personality change with frontal
lobe features that may, over years, be joined by parkinsonism
in a minority of cases.
Vascular parkinsonism is characterized by a gradually progressive
rigidity, bradykinesia, and gait abnormality, all
notably in the absence of tremor. This parkinsonism is typically
accompanied by signs of damage to the corticospinal and
corticobulbar tracts, such as spasticity, hyper-reflexia, and
pseudobulbar palsy. In some cases, a dementia may appear
(Bruetsch and Williams 1954; Keschner and Sloane 1931).
Dementia pugilistica has a gradual onset anywhere from
5 to 40 years after repeated head trauma (e.g., as in boxing),
with a combination of parkinsonism, dysarthria, ataxia,
and dementia (Harvey and Davis 1974; Martland 1928).
Fahr’s syndrome (Margolin et al 1980; Mathews 1957;
Nyland and Skre 1977) may present with parkinsonism
and dementia. Cerebellar signs such as dysarthria, intention
tremor, and ataxia may also be present, but the distinctive
finding is calcification of the basal ganglia, which is best
demonstrated on CT scanning.
Carbon monoxide intoxication may, after a lucid interval
of from days to weeks, be followed in a minority of cases by
the subacute onset of dementia and parkinsonism (Choi
1983; Min 1986).
Manganese intoxication, as may occur in those working
in manganese mines, steel mills, or battery factories, may
cause a gradually progressive parkinsonism that may be
joined by a dementia (Cook et al. 1974). The parkinsonism
in these cases is often marked by dystonic rigidity of the
neck and face and by ankle dystonia, which results in the
classic ‘cock-walk’ gait.
Methanol intoxication, as may occur in desperate
alcoholics, may, as a sequela, leave patients with dementia,
parkinsonism, and blindness (McLean et al. 1980).
Valproic acid, with chronic use, as for epilepsy or bipolar
disorder, may cause a combination of dementia and
parkinsonism, which is potentially reversible on discontinuation
of the drug (Armon et al. 1996; Shill and Fife 2000);
importantly, this side-effect of valproic acid may take from
6 months to 4 years to appear (Ristic et al. 2006).
Hypoparathyroidism may cause parkinsonism and
dementia but this is usually in the context of Fahr’s syndrome,
which, as noted above, includes calcification of the
basal ganglia. In one rare case, however, dementia and
parkinsonism occurred with hypoparathyroidism in the
absence of calcification and with a normal serum calcium
level. The only clue to the diagnosis was cataracts; the
parathyroid hormone level was low and the patient recovered
with dihydroxycholecalciferol (Stuerenburg et al. 1996).
Pantothenate kinase-associated neurodegeneration of
the late-onset type may present with a slowly progressive
parkinsonism that is eventually joined by dementia and
dystonia (Jankovic et al. 1985, Murphy et al. 1989).
Huntington’s disease of juvenile onset, seen in late
childhood or adolescence, may present with parkinsonism
and dementia (Bird and Paulson 1971; Campbell et al.
1961; Siesling et al. 1997).
Systemic lupus erythematosus very rarely presents with
a combination of dementia and parkinsonism (Dennis
et al. 1992).