CLINICAL AND RESEARCH REPORTS

Loss of Insight and

Functional Neuroimaging in
Frontotemporal Dementia
Mario F. Mendez, M.D., Ph.D.
Jill S. Shapira, R.N., Ph.D.
Loss of insight is a diagnostic criterion for frontotemporal dementia. It is associated with hypoperfusion/hypometabolism in the right hemisphere,
particularly the frontal lobe. Loss of insight is often an anosodiaphoria (i.e., lack of concern) rather
than an anosognosia (i.e., decreased awareness).
(The Journal of Neuropsychiatry and Clinical
Neurosciences 2005; 17:413416)

oss of insight is common in Alzheimers disease

(AD) and other dementias.17 Clinically, loss of insight means a denial or unawareness of symptoms or an
unconcern about the consequences of symptoms. Clinicians frequently use loss of insight synonymously with
anosognosia, a term originally used to describe reduced
awareness of hemiplegia in stroke patients and is now
applied to the reduced awareness of any symptom.9 In
dementia, the extent of anosognosia varies according to
the type of dysfunction, often being worse for memory
and other cognitive functions.1,2 Loss of insight in dementia occurs independent of the presence of depression or the psychological mechanisms of the denial of
illness.9
Loss of insight is particularly characteristic of early
frontotemporal dementia (FTD).10 Consensus criteria for
FTD include loss of insight as a core diagnostic feature
of the disorder,10 and patients with FTD display a
greater loss of insight into illness early in their dementia
when compared to patients with AD11 Compared to
other FTD patients, those patients with greater right
frontal disease have more apathy.12 This nding suggests that loss of insight in FTD may result from right
frontal disease and a loss of concern for their illness or
their behavioral changes rather than a true anosognosia.
This article examines the nature and association of loss
of insight with the changes on functional neuroimaging
among patients with FTD.

J Neuropsychiatry Clin Neurosci 17:3, Summer 2005

METHOD
Twenty-nine patients met diagnostic criteria for early
FTD based on consensus criteria (Table 1).10 Patients
were recruited from the University of California Los Angeles (UCLA) Focal-type Dementia Clinic. Each patient
agreed to participate in a program on FTD at the UCLA
Alzheimers Disease Center and signed an approved,
informed consent. The core criteria necessary for a clinical diagnosis of FTD are deceptive at onset. Gradual progression of early decline in social interpersonal conduct,
early impairment in regulation of personal conduct,
early emotional blunting, and early loss of insight takes
place.10 The clinical diagnosis in this study was corroborated by the presence of frontal or anterior temporal
predominant changes on functional neuroimaging.
As part of the evaluation, the FTD patients were
graded on their responses to the insight question (Tell
me why you are here?) taken from the Consortium to
Establish a Registry in AD (CERAD).13 Three additional
questions were used to generate responses to the
CERAD question. The three questions were: 1) Do you
have an illness or a problem that requires medical attention? 2) Is your behavior signicantly different now,

TABLE 1.

Frontotemporal Dementia (FTD): Patient

Characteristics

Numbers
Frontal/Temporal predominance
Sex (Male/Female)
Age in years
Education in years
Duration in years
MMSEa

Left-Sided
FTD

Right-Sided
FTD

13
8/5
7/6
61.4 (9.5)
14.9 (2.6)
2.7 (1.5)
22.9 (4.5)

16
10/6
9/7
59.5 (9.6)
15.2 (3.2)
2.3 (2.4)
23.9 (4.7)

a
Mini-Mental State Examination Scores
There were no differences in age, education, duration, or MMSE
scores when the patients were re-grouped as frontal predominant
versus temporal predominant

Received July 15, 2003; revised January 4, 2004; accepted March 16,
2004. From the Departments of Neurology and Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California. Address correspondence to Dr. Mendez, Neurobehavior Unit (116AF), VA Greater Los Angeles Healthcare System,
11301 Wilshire Blvd., Los Angeles, CA 90073; mmendez@UCLA.edu
(E-mail).
Copyright 2005 American Psychiatric Publishing, Inc.

http://neuro.psychiatryonline.org

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CLINICAL AND RESEARCH REPORTS

compared to a few years ago? 3) Do family/friends think
that you have an illness or that something is wrong with
you? The patients responses were graded on a 4-point
Likert scale of insight into illness and implications. The
grading scale was: normal or awareness of an illness or
a problem requiring medical attention (score3); partial
awareness or unawareness of illness or problem requiring medical attention but aware of a signicant change
in behavior (score2); unawareness or denial of both an
illness and a behavioral change but aware that family
and friends think that something is wrong (score1);
total unawareness or concern about health or behavior
(score0). Finally, patients were analyzed regarding
their knowledge of their behavior, and whenever they
endorsed an awareness of illness or behavioral changes,
they were asked to describe their degree of concern.
The results of the CERAD insight question were analyzed in terms of the predominant localization of
changes on functional neuroimaging. All of these early
FTD patients had asymmetric hypoperfusion or hypometabolism on single photon emission tomography
(SPECT) images or positron emission tomography (PET)
scans. Based on visual inspection of prominence of hypoperfusion or hypometabolism, the images were independently divided into left versus right hemispheric
laterality and frontal versus temporal quadrants by neuroimagers unfamiliar with the patients or their clinical
characteristics. These ndings were compared with the
results of the CERAD insight question using factorial
analysis of variance (ANOVA).

RESULTS
The characteristics of the FTD patients are summarized
in Table 2. Most patients denied having an illness or a
problem that required medical attention. However, all
patients were able to describe their behaviors when an-

TABLE 2.

alyzed. The patients could not convey a commensurate

concern about the consequences of their behavioral
symptoms and usually felt that these symptoms did not
represent disturbances, abnormalities, or signicant
changes from their usual patterns of behavior.
Representative behavioral comments illustrated the
nature of patients loss of insight. One patient stated, I
am shallow now . . . this bothers other people but not
me. Another patient would go into stores and restaurants and leave without paying for goods and services.
She could describe these episodes and the potential consequences, but she was not distressed or concerned
about her behavior. Several other patients conveyed the
same lack of concern for doing the right thing despite
knowing the difference. A patient with compulsive-like
behaviors stated, I do not care if people do not like it.
Another patient, who had become sexually disinhibited
and libertine, described specic encounters. She endorsed them as unacceptable but did not express appropriate concern, even for the potential impact on her children.
On the SPECT and PET scans, 13 patients had predominant left-sided hypoperfusion or hypometabolism,
and 16 had predominant right-sided hypoperfusion or
hypometabolism. Ten of the right-sided patients had
greater frontal hypoperfusion or hypometabolism than
temporal hypoperfusion or hypometabolism, and six
had greater temporal changes. Eight of the left-sided patients had more frontal changes than temporal changes,
and ve had greater temporal changes. The main effect
of the ANOVA was signicant (F(2, 25) 16.36,
p0.001), and there was a laterality effect (F(1, 25)
19.81, p0.01) and a frontal versus temporal predominance effect (F(1, 25) 13.36, p0.01) but no statistically signicant interaction. Despite the lack of a statistically signicant interaction, the greatest loss of insight
occurred among the right frontal predominant FTD patients.

Results of CERAD Insight Questiona by Laterality and Localization

Frontal predominant
Temporal predominant

Left Hemisphere
Predominant

Right Hemisphere
Predominant

1.50 (0.53)
n8
2.00 (0.0)
n5
1.69 (0.48)

0.30 (0.48)
n10
1.33 (0.82)
n6
0.69 (0.79)

0.83 (0.79)
1.64 (0.67)
1.14 (0.83)

a
Consortium to Establish a Registry in Alzheimers disease insight question was graded on a 4-point scale. Laterality and frontotemporal
differences were signicantly different (p.01), but the interaction was not statistically signicantly different.

414

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J Neuropsychiatry Clin Neurosci 17:3, Summer 2005

MENDEZ and SHAPIRA

DISCUSSION
It is not surprising that FTD is characterized by loss of
insight.10 In dementia, patients who lack insight of their
cognitive and functional decits may be indifferent
about their emotional response toward their condition.5
In the present, we found that the loss of insight in FTD
was greatest in those with right hemispheric hypoperfusion/hypometabolism, particularly in the frontal lobe.
In many of these patients, the loss of insight could be
more properly described as indifference or anosodiaphoria rather than anosognosia.
Among the dementias, investigators have primarily
studied loss of insight in AD, where it is related to deficits in frontal functions, especially on the right.4,6 In
AD, the most consistent correlations between impaired
insight and neuropsychological tests were regarding
frontal-executive tasks such as the Wisconsin Card Sorting Test, verbal uency, Lurias graphic series, Mazes,
and the Trailmaking Tests.2,14 Loss of insight was highly
correlated with a frontal score that included frontal behaviors such as prehension, utilization, imitation, inertia, and indifference.14 In addition, most SPECT studies
in AD patients with loss of insight report signicant
blood ow decits in the right hemisphere, especially
the frontal inferior and dorsolateral areas.5,6,15
Loss of insight can result from various mechanisms.
Anosognosia refers to a true recognition defect in which
the patient is unaware of or has impaired knowledge of
acquired symptoms and behaviors.8 Anosognosia generally results from damage to the right inferior parietal
lobule and is often dened as a discrepancy between a

patients report of disability and any objective evidence

regarding impairment. In contrast, anosodiaphoria refers to the condition in which patients are unconcerned
with or signicantly minimize the extent of their decits.8
There are several limitations to this preliminary study.
First, the numbers of FTD patients per quadrant (laterality and frontotemporal) were relatively small and may
have masked a frontal-right hemispheric interaction.
Second, the addition of neuropsychological measures
could lend validity to the regional ndings from functional neuroimaging. Finally, although the method of
image analysis based on laterality and frontotemporal
quadrants allows for a simple categorization of predominant lateralization and localization, it restrains the capacity to consider multiple regions of change.
In conclusion, loss of insight in FTD may be a function
of right hemisphere disease, especially in the frontal
lobe, and is at least partially due to patients lack of concern for their illness or symptoms. Characterization of
the nature of loss of insight in FTD has management
implications, as it affects functional performance and
decline. Further studies into the relation between loss of
insight and focal pathophysiology may clarify the underlying mechanisms responsible for loss of insight
from right frontal dysfunction.

This study was supported by NIA P01 AG1972401A1

(Bruce L. Miller, P.I.) and the UCLA Alzheimers Disease
Center.

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