Dementia associated with infectious diseases

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International Psychogeriatrics (2005), 17:Supp., S65–S77 C _ 2005

International Psychogeriatric Association

doi:10.1017/S104161020500195X Printed in the United Kingdom

The full text is available from the authors or the publisher.

Dementia associated with infectious diseases

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Osvaldo P. Almeida and Nicola T. Lautenschlager

School of Psychiatry and Clinical Neurosciences, University of Western

Australia, Australia

ABSTRACT

At the turn of the last century, infectious diseases represented an important

cause of health morbidity and behavioral changes. Neurosyphilis, for example,

was relatively common at the time and often led to the development of

cognitive

impairment and dementia. With the advent of effective antibiotic treatment,

the

association between infectious diseases and dementia became increasingly less

frequent, although a resurgence of interest in this area has taken place

during

the past 15 years with the emergence of acquired immunodeficiency syndrome

(AIDS) and variant Creutzfeldt–Jakob disease (vCJD). This paper reviews

the most frequent infectious causes of dementia, including prion diseases,

as well as infections caused by herpes virus, human immunodeficiency virus

(HIV), toxoplasmosis, cryptococcus, cytomegalovirus, syphilis, borrelia and

cysticercosis.

Key words: cognitive impairment, prion diseases, herpes, AIDS, toxoplasmosis,

syphilis, Lyme disease,

neurocysticercosis

Introduction

Infectious diseases are relatively common in our society and, in later life,

are

frequently associated with delirium. The central nervous system can be

infected

by prions, viruses, bacteria, fungi and parasites. While confusional states

are

common, clear dementia syndromes due to infections are rare, particularly

since effective antib! iotic treatment has become widely available. However,

with

the advent of human immunodeficiency virus (HIV) infection, some of the

" historical " causes of dementia, such as neurosyphilis, have re-emerged and

now feature alongside modern infectious causes of mental disorders, such as

variant Creutzfeldt–Jakob disease. This paper provides an overview of the

most

frequent infectious agents associated with cognitive impairment.

Neurosyphilis

CNS infections with the spirochete Treponema pallidum have decreased

significantly with the introduction of penicillin, but still represent an

important,

but relatively rare, cause of dementia. The clinical presentation of patients

with

neurosyphilis is varied, and includes asymptomatic neurosyphilis,! acute

syphilitic

meningitis, subacute and chronic meningovascular syphilis, tabes dorsalis,

and

general paralysis. General paralysis is the clinical presentation of

neurosyphilis

most frequently associated with dementia, although untreated patients with

tabes dorsalis and meningovascular syphilis may also develop dementia with

the

progression of the illness. Patients with general paralysis often present

with

symptoms of emotional incontinence, irritability, grandiosity, euphoria, poor

insight, apathy, delusions or cognitive impairment (Cummings and Benson,

1992; Dewhurst, 1969; Fr¨oshaug and Ytrehus, 1956; Hahn and , 1946;

, 1940). Tremor, dysarthria and Argyll–on pupils can also be

observed. As the disease and the dementia progress, ataxia, spastic paralysis

and

seizures may further complicate the management of these patients. The

underlying pathology of neurosyphilis involves diffuse inflammatory

processes of the cerebrovascular system and the meninges, which can also lead

to cranial nerve lesions, hydrocephalus, hypothalamic involvement, epilepsy

and

strokes. Tabes dorsalis is characterized by degeneration of the ascending

fibers

from the dorsal root ganglia, which ultimately affects the posterior columns

of the

cord. By contrast, general paralysis leads to a dementia syndrome with

gradual

onset that is typically associated with frontotemporal signs. In

approximately

20% of patients, however, the clinical symptoms of tabes dorsalis and general

paralysis may coexist.

Neuroimaging studies may reveal frontal and/or temporal lobe atrophy,

subcortical changes and cerebral infarctions (Brightbill et al., 1995; Zi!

fko et al.,

1996). The fluorescent treponemal antibody absorption test (FTA-ABS) shows

good reactivity to tertiary syphilis (Simon, 1985), but can produce false

positive results in the presence of other infectious diseases or systemic

lupus

erythematosus; therefore, a good history of any previous treatment is

required

with a CSF examination (Hook and Marra, 1992). The CSF in neurosyphilis

frequently shows lymphocytic pleocytosis, elevated protein, increased

immunoglobulin G and a positive Venereal Disease Research Laboratory

test. Treatment of choice is with penicillin, preferably intravenous, and for

a

minimum period of 10, and preferably 15, days (Hook andMarra, 1992). Initial

treatment can be associated with worsening of neurological signs and the

Jarish–

Herxheimer reaction. For ! this reason corticosteroids are often

concomitantly

prescribed for the first few days of treatment. Follow-up assessments are

necessary.

Case reports and clinical experience suggest that treatment with penicillin

can arrest and, in some cases, reverse some of the cognitive deficits,

particularly

when treatment is introduced early in the course of the illness.

Of note, patients with neurosyphilis associated with HIV infection may have

faster disease progression and a poorer prognosis than non-HIV-infected

patients

(Fox et al., 2000).

Lyme disease

Lyme disease is caused by the spirochaete Borrelia burgdorferi and is usually

transmitted by tick bites. The inf! ection becomes apparent 3–32 days after

exposure

with a characteristic acute rash (erythema migrans) surrounding the tick

bite area. Approximately 10–15% of patients develop neurological symptoms,

such as chronic meningitis, progressive encephalomyelitis, encephalopathy,

radiculopathy, monomeuritis multiplex, myopathy, cranial neuropathies

(usually

the seventh nerve), seizures and occasionally mild cognitive impairment

(Finkel

and Halperin, 1992).

The cognitive impairment of patients with Lyme disease is characterized by

impaired executive function and reduced attention (Benke et al., 1995; Waniek

et al., 1995). A clear dementia syndrome, however, seems to be an infrequent

consequence of Lyme disease (Halperin et al., 1991). Depression, emotional

lability, irritability and psychosis may also be present (Fallon and Nields,

1994).

As serological tests for B. burgdorferi are not sufficiently reliable, CSF

examination may be required. The CSF often shows pleocytosis, elevated

protein

levels, oligoclonal bands and borrelial DNA (O’Connell, 1995). Neuroimaging

with MRI can show increased signal in the white matter indicating focal

demyelination. Neuropathological findings include demyelinization,

vasculitis,

neuronal loss, gliosis and brain parenchyma infections (Halperin et al.,

1991).

In the presence of neurological symptoms, parenteral antibiotic treatment is

recommended (Muhlemann, 1992).