Secondary Schizophrenia (82 page)

Delusions and hallucinations

might be due to the fact that psychotic symptoms are
• Higher neuronal counts the parahippocampal gyrus and
harder to detect in patients with severe AD due to their
lower counts in the dorsal raphe nucleus [44].

reduced abilities to communicate. On the other hand,
• Higher neurofibrillary burden [51].

it is also possible that the severely reduced mental abil-

• Genetic variations of 5-hydroxytryptamine (5-HT) receptors
ities of these patients no longer allow them to gener-

[52].

ate these symptoms. Risk factors may differ between
• Genetic variations of dopaminergic receptors [53].

delusions and hallucinations. Bassiony and colleagues,
• Elevation of glycerophosphoethanolamine and reduction of
for example, found in a cross-sectional study of 342

N-acetyl-L-aspartate [54].

community-dwelling patients with AD that delusions
• Metabolic and perfusion abnormalities in frontal, temporal,
were associated with poor general health, older age,
and parietal cortex [34, 55, 56, 57].

aggression, and depression, whereas hallucinations
• Left-and right-brain hemisphere differences in size, blood
were associated with more severe cognitive impair-flow, and glucose metabolism [58].

ment and longer disease course, falls, lower education,
• Cholinergic-serotonergic imbalance [59].

and African-American race
[42, 43].

(Boston naming test) and a memory task (CVLT

Neurobiological factors

delayed recognition). The authors hypothesized that
A variety of hypotheses have been discussed on how
the reduced capability to perform frontal lobe func-neurobiological factors contribute to the develop-tions prevented successful self-monitoring and real-ment of psychotic symptoms in AD. An overview on
ity testing, which impaired the individual’s abilities
reported associations is presented in
Table 15.4.

to interpret and integrate experiences
[63, 64, 65].
It
has been suggested that relatively preserved language
Neuropsychological profile

and memory functions might be necessary “to rehearse
The published literature suggests that AD patients
and store incorrect hypotheses or judgements as ‘long-with psychotic symptoms experience more significant
term memory traces’ to produce delusions”
[64].

impairment in neuropsychological functions compared to AD patients free from psychotic symptoms
Genetic factors

[41,
60, 61, 62],
with some exceptions
[59].
Paulsen and
It has been suggested that genetic factors might
colleagues suggested that AD patients with psychotic
increase the susceptibility for AD with psychotic
symptoms had more neurobehavioral dysfunction

symptoms as a specific phenotype
[14,
54,
66, 67, 68,

such as disinhibition, which is connected to frontal
69]
. Sweet and colleagues reported in a case-control
lobe impairment
[40].
When Hopkins and Libon com-study, with 371 patients with AD and psychotic symp-pared 24 outpatients with AD or vascular dementia
toms and their 461 siblings, that the risk for AD with
with psychosis with 24 outpatients without psychosis,
psychosis for the siblings was significantly increased
they found that patients with psychosis performed less
with OR
=
2.41 (95% CI
=
1.46–4.0, p
=
.0006)
[54].

well in executive control measured with the mental
Bacanu and colleagues estimated, with data from
control subtest of the Wechsler Memory Scale (F [3, 43]

the National Institute of Mental Health AD Genetics
=
4.17, p < .001)
[63].
Interestingly, they performed
Initiative on 826 patients with AD, that heritability for
207

better than nonpsychotic patients on a language task
siblings for AD patients who displayed at least one
Organic Syndromes of Schizophrenia – Section 3

symptom of psychosis during their illness was 30%,
symptoms or subsyndromal psychotic symptoms prior
and for siblings of AD patients with multiple psychotic
to diagnosis of AD. The authors identified “elevated
symptoms was 61%
[68].
Two popular hypotheses to
schizotypal personality scores” in those participants
explain findings of increased heritability of psychosis
who later displayed psychotic symptoms in the course
in AD are: (i) AD with psychotic symptoms repre-of their illness at “trend level” (p
=
.06) and a sig-sents a “purer” or “less heterogeneous form of AD” or
nificant association between “severity of schizotypal
(ii) susceptibility for psychosis is a “quantitative trait
symptoms and multiple psychotic symptoms during
in the population” that can emerge either because of
AD” (p
=
.008). They suggested that schizotypal per-environmental factors or an increased vulnerability of
sonality symptoms during life change into clinical sig-the brain because of neurodegeneration
[69].
Interest-nificant psychotic symptoms in the context of a neu-ingly, Bacanu and colleagues reported, in studies with
rodegenerative process
[73].
The retrospective nature
families of AD patients with psychosis, linkages to loci
of the study, however, raises concerns regarding recall
on chromosome 2p and 6p that have also been iden-bias for the caregiver who frequently gave the infor-tified for schizophrenia
[67].
Rare types of autosomal-mation after having observed psychotic symptoms in
dominant inherited forms of familial AD can present
their demented next of kin.

early in the disease course with psychotic symptoms.

Rippon and colleagues reported an African-American
Environment

family with a presenilin 1 point mutation (M139V) in
In addition to sensory deficits
[74, 75],
the environ-which affected family members developed a rapidly
ment the patient is exposed to might contribute to the
progressive dementia with personality change, delu-development and persistence of psychotic symptoms.

sions, and auditory and visual hallucinations
[70].

Insufficient illumination indoors was identified as
There have been conflicting results for the association
an important risk factor
[76],
and bright light therapy
of the apolipoprotein E genotype and psychotic symp-has been reported as being effective in reducing psy-toms in AD
[58,
71].

chotic symptoms in AD
[77].
The behavior and coping
Personality

skills of the caregiver represent additional environmental factors that have been shown to have an effect
More recently, it has been suggested that symptoms of
on psychotic symptoms
[78].

psychosis may be present before a diagnosis of dementia has been established as part of a prodromal syndrome or on a subsyndromal level as part of a per-

Cognitive and functional decline, institutionalization,

sonality structure. ¨

Ostling and colleagues conducted

and mortality

a prospective population-based study in Göteborg,
Numerous authors have described a more rapid cog-Sweden, and observed 305 nondemented older adults
nitive
[61, 79, 80, 81, 82, 83, 84, 85,
86]
or func-for psychotic symptoms.

tional decline
[61,
86, 87, 88]
in psychotic patients
Participants received neuropsychiatric and medi-with AD compared to those without psychotic symp-cal assessments at ages 85 and 88 years, which included
toms, although this is not a consistent finding for either
an interview with a next of kin
[72].
Sixty-three par-rapid cognitive
[12,
61,
88, 89, 90, 91]
or functional
ticipants developed a dementia syndrome on follow-decline
[90, 92].
The discrepancy may be accounted
up. Delusions (OR
=
2.7; 95% CI
=
1.2–6.2), hallu-for by differences in ascertainment, criteria for diag-cinations (OR
=
3.1; 95% CI
=
1.24–6.8), and para-nosing psychotic symptoms, infrequency of assess-noid ideations (OR
=
2.7; 95% CI
=
1.2–6.2) were
ments, dementia severity, and variations in treatment.

all associated with an increased incidence of dementia
Jeste and colleagues reported that patients with psy-from the first to the second assessment. Eror and col-chotic symptoms in their study
[41]
tended to have
leagues investigated prodromal psychotic symptoms in
a more severe dementia with especially poorer pera retrospective study with 61 patients with probable
formance on fronto temporal cognitive tests, despite
and possible AD
[73].
Fifty-one percent were classi-a similar duration of illness compared to those with-fied as “ever psychotic,” whereas 26% had displayed
out psychotic symptoms. The authors interpreted
“multiple psychotic symptoms” during their illness so
this as indicating that patients with psychotic symp-far. Primary care givers were asked in a standard-toms might experience a more rapid decline. Stern
208

ized way whether the patient had shown psychotic
and colleagues observed in a prospective study with
Chapter 15 – Neurodegenerative disorders

266 participants that patients with AD and psychosis
They give as possible explanations the possibility of a
had a more rapid cognitive decline (declined 1.15

higher neuropathological burden, higher risk-taking
points more on the mMMS per 6-month interval; 95%

behavior, and lower level of attention to medical prob-CI
=
0.52–1.77) compared to patients with AD with-lems in patients who hallucinate.

out psychosis
[60].

Psychotic symptoms are frequently associated with
Implications for clinical practice

agitated and aggressive behavior
[38,
85,
93]
and there-The medical care of patients with AD should include
fore often contribute to increased caregiver burden
a regular screening for psychotic symptoms with the
[94, 95]
and early institutionalization
[87, 96, 97].

help of structured interview questionnaires such as
Stern and colleagues followed 236 patients with AD

the NPI. It has been suggested that roughly a third of
at 3 research centers in the United States for up to
patients with AD are significantly distressed by their
7 years to determine predictive factors for nursing
psychotic symptoms
[99].
In these cases, early identi-home admission and death
[97].
Delusions and hal-fication and management are crucial to improve qual-lucinations were assessed with a semistructured inter-ity of life and nonpharmacologic management is con-view (the Columbia University Scale for Psychopathol-sidered the first line of treatment
[100]
. On the other
ogy in Alzheimer’s Disease, CUSPAD) during the
hand, if patients are not distressed by psychotic symp-month prior to the assessment. The CUSPAD asked
toms and are not acting on them in a way that would
for paranoid delusions, delusions of abandonment,
increase health risks for themselves or others, manage-somatic delusions, and misidentifications. One hun-ment of these symptoms is not necessarily warranted.

dred and three patients had one or more psychotic
If psychotic symptoms are identified, a more thorough
symptoms at baseline. Cox proportional hazard mod-medical check-up may be indicated to avoid overlook-els showed that the presence of psychotic symptoms at
ing a superimposed delirium.

baseline was associated with a significantly increased
risk for requiring nursing home care in the future
(RR
=
1.50; 95% CI
=
1.04–2.15).

Suggestions for future research

Interestingly, patients with psychotic symptoms
An important goal within the vast research field of
did not have a significant higher mortality. One of
AD will be to refine diagnostic criteria for specific
the most recent studies on the association of pres-neuropsychiatric symptoms, such as psychosis in AD

ence of psychotic symptoms and disease course in
[101]
. With growing knowledge, especially from lon-AD is a large multicenter study by Scarmeas and col-gitudinal studies, it is likely that more subtypes will be
leagues
[98].
The authors described psychotic symp-identified with a clearer understanding of the relation-toms in 456 patients with mild AD who were fol-ship of the presentation of psychotic symptoms and
lowed from 0.11 to 14 years. Patients were assessed
disease course. Already there seems to be some evion average seven times, usually at 6-month intervals.