Insight Fronto Temporal Insight

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J Neuropsychiatry Clin Neurosci 17:3, Summer 2005 http://neuro.psychiatryonline.org 413

CLINICAL AND RESEARCH REPORTS

TABLE 1. Frontotemporal Dementia (FTD): PatientCharacteristics

Left-SidedFTD

Right-SidedFTD

Numbers 13 16Frontal/Temporal predominance 8/5 10/6Sex (Male/Female) 7/6 9/7Age in years 61.4 (9.5) 59.5 (9.6)Education in years 14.9 (2.6) 15.2 (3.2)Duration in years 2.7 (1.5) 2.3 (2.4)MMSEa 22.9 (4.5) 23.9 (4.7)

a Mini-Mental State Examination ScoresThere were no differences in age, education, duration, or MMSE

scores when the patients were re-grouped as frontal predominantversus temporal predominant

Received July 15, 2003; revised January 4, 2004; accepted March 16,2004. From the Departments of Neurology and Psychiatry & Biobe-havioral Sciences, David Geffen School of Medicine at UCLA, Los An-geles, California. Address correspondence to Dr. Mendez, Neurobe-havior Unit (116AF), VA Greater Los Angeles Healthcare System,11301 Wilshire Blvd., Los Angeles, CA 90073; [email protected](E-mail).

Copyright 2005 American Psychiatric Publishing, Inc.

Loss of Insight and

Functional Neuroimaging inFrontotemporal Dementia

Mario F. Mendez, M.D., Ph.D. Jill S. Shapira, R.N., Ph.D.

Loss of insight is a diagnostic criterion for fronto-temporal dementia. It is associated with hypoper-

fusion/hypometabolism in the right hemisphere,particularly the frontal lobe. Loss of insight is of-ten an anosodiaphoria (i.e., lack of concern) ratherthan an anosognosia (i.e., decreased awareness).

(The Journal of Neuropsychiatry and ClinicalNeurosciences 2005; 17:413–416)

Loss of insight is common in Alzheimer’s disease

(AD) and other dementias.1–7 Clinically, loss of in-

sight means a denial or unawareness of symptoms or an

unconcern about the consequences of symptoms. Clini-

cians 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 tothe type of dysfunction, often being worse for memory

and other cognitive functions.1,2 Loss of insight in de-

mentia occurs independent of the presence of depres-

sion 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 finding sug-

gests 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.

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 An-

geles (UCLA) Focal-type Dementia Clinic. Each patient

agreed to participate in a program on FTD at the UCLA

Alzheimer’s Disease Center and signed an approved,

informed consent. The core criteria necessary for a clini-

cal diagnosis of FTD are deceptive at onset. Gradual pro-

gression 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 corrob-orated 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 atten-

tion? 2) Is your behavior significantly different now,



414 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 17:3, Summer 2005


TABLE 2. Results of CERAD Insight Questiona by Laterality and Localization

Left HemispherePredominant

Right HemispherePredominant

Frontal predominant 1.50 (0.53)n8

0.30 (0.48)n10

0.83 (0.79)

Temporal predominant 2.00 (0.0)n5

1.33 (0.82)n6

1.64 (0.67)

1.69 (0.48) 0.69 (0.79) 1.14 (0.83)

a Consortium to Establish a Registry in Alzheimer’s disease insight question was graded on a 4-point scale. Laterality and frontotemporaldifferences were significantly different (p.01), but the interaction was not statistically significantly different.

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); partialawareness or unawareness of illness or problem requir-

ing medical attention but aware of a significant 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 an-

alyzed in terms of the predominant localization of changes on functional neuroimaging. All of these early

FTD patients had asymmetric hypoperfusion or hypo-

metabolism on single photon emission tomography

(SPECT) images or positron emission tomography (PET)

scans. Based on visual inspection of prominence of hy-

poperfusion or hypometabolism, the images were in-

dependently divided into left versus right hemispheric

laterality and frontal versus temporal quadrants by neu-

roimagers unfamiliar with the patients or their clinical

characteristics. These findings 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-

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 significant

changes from their usual patterns of behavior.

Representative behavioral comments illustrated thenature 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 restau-

rants and leave without paying for goods and services.

She could describe these episodes and the potential con-

sequences, 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 specific encounters. She en-dorsed them as unacceptable but did not express appro-

priate concern, even for the potential impact on her chil-

dren.

On the SPECT and PET scans, 13 patients had pre-

dominant 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 pa-

tients had more frontal changes than temporal changes,

and five had greater temporal changes. The main effectof the ANOVA was significant (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 predomi-

nance effect (F(1, 25) 13.36, p0.01) but no statisti-

cally significant interaction. Despite the lack of a statis-

tically significant interaction, the greatest loss of insight

occurred among the right frontal predominant FTD pa-

tients.



J Neuropsychiatry Clin Neurosci 17:3, Summer 2005 http://neuro.psychiatryonline.org 415

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 deficits 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 hypoper-

fusion/hypometabolism, particularly in the frontal lobe.

In many of these patients, the loss of insight could be

more properly described as indifference or anosodia-

phoria rather than anosognosia.

Among the dementias, investigators have primarily

studied loss of insight in AD, where it is related to def-

icits 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 Sort-ing Test, verbal fluency, Luria’s graphic series, Mazes,

and the Trailmaking Tests.2,14 Loss of insight was highly

correlated with a frontal score that included frontal be-

haviors such as prehension, utilization, imitation, iner-

tia, and indifference.14 In addition, most SPECT studies

in AD patients with loss of insight report significant

blood flow deficits 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 gen-erally results from damage to the right inferior parietal

lobule and is often defined as a discrepancy between a

patient’s report of disability and any objective evidence

regarding impairment. In contrast, anosodiaphoria re-

fers to the condition in which patients are unconcerned

with or significantly minimize the extent of their defi-

cits.8

There are several limitations to this preliminary study.First, the numbers of FTD patients per quadrant (later-

ality 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 findings from func-

tional neuroimaging. Finally, although the method of

image analysis based on laterality and frontotemporal

quadrants allows for a simple categorization of predom-

inant lateralization and localization, it restrains the ca-

pacity to consider multiple regions of change.

In conclusion, loss of insight in FTD may be a functionof right hemisphere disease, especially in the frontal

lobe, and is at least partially due to patients’ lack of con-

cern 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 un-

derlying mechanisms responsible for loss of insight

from right frontal dysfunction.

This study was supported by NIA P01 AG19724–01A1(Bruce L. Miller, P.I.) and the UCLA Alzheimer’s DiseaseCenter.

References

1. Green J, Goldstein FC, Sirockman BE, et al: Variable awarenessof deficits in Alzheimer’s disease. Neuropsychiatry Neuropsy-chol Behav Neurol 1993; 6:159–165

2. Ott BR, Lafleche G, Whelihan WM, et al: Impaired awareness of deficits in Alzheimer disease. Alzheimer Dis Assoc Disord 1996;10:68–76

3. Kotler-Cope S, Camp CJ: Anosognosia in Alzheimer disease.Alzheimer Dis Assoc Disord 1995; 9:52–56

4. Lopez OL, Becker JT, Somsak D, et al: Awareness of cognitivedeficits and anosognosia in probable Alzheimer’s disease. EurNeurol 1994; 34:277–282

5. Ott BR, Noto RB, Fogel BS: Apathy and loss of insight in Alz-heimer’s disease: a SPECT imaging study. J NeuropsychiatryClin Neurosci 1996; 8:41–46

6. Reed BR, Jagust WJ, Coulter L: Anosognosia in Alzheimer’s dis-ease: relationship to depression, cognitive function, and cerebralperfusion. J Clin Exp Neuropsychol 1993; 15:231–244

7. Vasterling JJ, Seltzer B, Foss JW, et al: Unawareness of deficit inAlzheimer’s disease-domain specific differences and disease

correlates. Neuropsychiatry Neuropsychol Behav Neurol 1995;8:26–32

8. Tranel D: Functional neuroanatomy. Neuropsychological corre-lates of cortical and subcortical damage, in The American Psy-chiatric Publishing Textbook of Neuropsychiatry and ClinicalNeurosciences, 4th ed, by Yudofsky SC, Hales RE. Ed. Washing-ton, DC, American Psychiatric Publishing, Inc, 2002, pp 93

9. Smith CA, Henderson VW, McCleary CA, et al: Anosognosia

and Alzheimer’s disease: the role of depressive symptoms inmediating impaired insight. J Clin Exp Neuropsychol 2000;22:437–444

10. Neary D, Snowden JS, Gustafson L, et al: Frontotemporal lobardegeneration: a consensus on clinical diagnostic criteria. Neu-rology 1998; 51:1546–1554

11. Gustafson L: Clinical picture of frontal lobe degeneration of non-Alzheimer type. Dementia 1993; 4:143–148

12. Boone KB, Miller BL, Swartz R, Lu P, Lee A: Relationship be-tween positive and negative symptoms an neuropsychological



416 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 17:3, Summer 2005


scores in frontotemporal dementia and Alzheimer’s disease. JInt Neuropsychol Soc 2003; 9:698–709

13. Welsh KA, Butters N, Mohs RC, et al: The consortium to estab-lish a registry in Alzheimer’s disease (CERAD), part V, A nor-mative study of the neuropsychologicalbattery. Neurology 1994;44:609–614

14. Michon A, Deweer B, Pillon B, et al: Relation of anosognosia tofrontal lobe dysfunction in Alzheimer’s disease. J Neurol Neu-rosurg Psychiatry 1994; 57:805–809

15. Starkstein SE, Vazquez S, Migliorelli R, et al: A single-photonemission computed tomographic study of anosognosia in alz-heimer’s disease. Arch Neurol 1995; 52:415–420

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Insight Fronto Temporal Insight