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J Neurol Neurosurg Psychiatry 79:176-179 doi:10.1136/jnnp.2007.122853
  • Short report

A comparison of unawareness in frontotemporal dementia and Alzheimer’s disease

  1. E Salmon1,
  2. D Perani2,
  3. F Collette1,
  4. D Feyers1,
  5. E Kalbe3,
  6. V Holthoff4,
  7. S Sorbi5,
  8. K Herholz3,6
  1. 1
    Cyclotron Research Center, University of Liege, Liège, Belgium
  2. 2
    Vita Salute San Raffaele University, IRCCS H San Raffaele, IBFM-CNR, Milan, Italy
  3. 3
    Department of Neurology, University of Cologne, Germany
  4. 4
    Department of Psychiatry and Psychotherapy, Dresden University of Technology, Dresden, Germany
  5. 5
    Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
  6. 6
    Wolfson Molecular Imaging Centre, University of Manchester, UK
  1. Eric Salmon, Cyclotron Research Center, University of Liège, B30 Sart Tilman, 4000 Liège, Belgium; eric.salmon{at}ulg.ac.be
  • Received 18 April 2007
  • Revised 3 September 2007
  • Accepted 13 September 2007
  • Published Online First 26 September 2007

Abstract

Background: Loss of insight is a core diagnostic feature of frontotemporal dementia (FTD) and anosognosia is frequently reported in Alzheimer’s disease (AD).

Aim: To compare unawareness (anosognosia) for different symptoms, measured with a discrepancy score between patient’s and caregiver’s assessment, in AD and FTD.

Method: In a prospective, multi-centre study, 123 patients with probable AD, selected according to the NINCDS-ADRDA procedure, were matched for age, sex, education, disease duration and dementia severity to patients with FTD (n = 41), selected according to international consensus criteria. A research complaint questionnaire was used to obtained patient’s and caregiver’s assessment concerning neuropsychological and behavioural symptoms. Data were compared in each group and between groups. Unawareness (measured by discrepancy scores) was compared between patients with AD and FTD.

Results: The caregivers generally assessed symptoms more severely than did patients, but both patient groups reported changes in affect (depressive mood or irritability) as their caregivers did. Unawareness was greater in patients with FTD than in patients with AD for language and executive difficulties, and for changes in behaviour and daily activities.

Conclusion: The main finding is that unawareness was observed in both patients with FTD and patients with AD for most clinical domains. However, qualitative and quantitative differences showed that lack of awareness was greater in patients with FTD.

Lack of awareness, anosognosia or loss of insight are used to describe the impaired judgment of patients with dementia concerning their own cognition, mood, behaviour or daily activities. Questionnaires are frequently used in the literature to assess lack of awareness of dementia symptoms. A discrepancy score, calculated between answers obtained from the patient and from a caregiver, constitutes a measure of anosognosia.1

In frontotemporal dementia (FTD), loss of insight into the clinical status is a core diagnostic feature.2 Patients with FTD are shown to lack behavioural self-awareness,3 and they have some difficulties in adequately judging their cognitive performances.4

Anosognosia occurs early in some patients with Alzheimer’s disease (AD).5 The degree of awareness is variable for different domains of the dementia syndrome.5 Lack of awareness of patients with AD was correlated to dementia severity in most, but not all, studies.68

Loss of insight was reported to be more important in patients with FTD than in patients with AD9 10 and it contributes to the discrimination between both dementia groups.11 Comparison of discrepancy scores concerning neuropsychological symptoms in patients with AD and FTD is not yet available.

We aimed to study unawareness in a large number of carefully matched patients with probable FTD and AD included in a European research programme (Network for Efficiency and Standardization of Dementia Diagnosis or NEST-DD). A research questionnaire on cognitive abilities and behavioural symptoms was used,5 and a comparison was made between the subjective judgment of a caregiver and the self-assessment of the patient about his abilities. We were interested in assessing the difference in judgment for each clinical domain in both dementia groups, and to compare discrepancy scores reflecting unawareness of dementia symptoms in patients with AD and FTD.

METHODS

Patients prospectively included in the NEST-DD protocol were consecutive cases with suspected dementia who were referred for diagnostic evaluation.5 The study was approved by a local Ethics Committee in each participating centre. Clinicians made a diagnosis of probable AD12 or FTD2 based on demographic information, clinical history, neurological and neuropsychological examination, recent anatomical neuroimaging (CT or MRI) and laboratory data. Patients with FTD showed the behavioural presentation of the disease (the frontal variant).

Population

We included 41 patients with FTD and 123 patients with AD. Functional imaging confirmed predominant anterior brain metabolic impairment in the FTD group.13 Demographic and principal neuropsychological and behavioural data are presented in table 1. The groups were matched for age, education, disease duration and dementia stage.

Table 1 Demographic and general clinical data in patients with Alzheimer’s disease and frontotemporal dementia

EXPERIMENTAL QUESTIONNAIRE FOR PATIENT AND CAREGIVER

An experimental questionnaire was designed for NEST-DD, to obtain patient and caregiver assessments of impairments in multiple cognitive and behavioural domains for each patient.5 7 The selected domains comprised memory, temporal and spatial orientation, attention, verbal fluency, word finding, executive function, abstract thinking, calculation, affect, behaviour and daily activities. For each domain, rating corresponded to 5 levels: no complaints (1), mild (2), moderate difficulties (3), or severe problems (4), and very severe impairment (5). The principle of the rating was explained to the patient, who was explicitly required to refer to the last months when making evaluation. Patients had to be well awake, cooperative and they had to understand the meaning of the rating to start the questionnaire. Then, stereotyped questions were proposed to describe the domain being assessed (for example, to assess attention or distraction: “do you (does he/she) have problems in following a conversation or in concentrating on reading or watching TV? Do you (does he/she) easily get distracted?”). Patients were subsequently asked to rate recent difficulties in the given domain (see supplementary material). Three variables were analysed: the score corresponding to caregiver evaluation of the patient’s cognitive or behavioural impairment, the score reflecting self evaluation of the patient, and a discrepancy score calculated by subtraction of patient from caregiver score (measuring unawareness). Moreover, we capitalised on a previous study in AD7 to perform a multiple regression analysis in the FTD population, with the discrepancy score concerning cognitive domains as the dependent variable and twelve demographic, neuropsychological and behavioural independent variables (taken from table 1).

Statistics

Mann–Whitney U or chi-square tests and multiple regression analysis were performed in Statistica (StatSoft, France; http://www.statsoft.com). The significant level was set at p<0.05, and we also report values corrected for multiple comparisons between the two groups. Non-parametrical tests were chosen because several variables were not normally distributed. For the variables normally distributed, a repeated-measures ANOVA (groups = AD and FTD; measure = caregiver’s and patient’s evaluation) essentially gave the same results.

RESULTS

Mean rating

In AD, the mean value of patients’ assessment concerning their neuropsychological and behavioural impairment (1.8±0.6) was significantly lower than their caregiver’s rating (2.2±0.6). Similarly, the mean rating of patients with FTD concerning their impairment (1.7±0.6) appeared to underestimate the impairment reported by their caregivers (2.4±0.7). There was no difference between the mean rating of patients from the two dementia groups, or between the mean rating of their caregivers. The mean total discrepancy score (measuring anosognosia) was higher in patients with FTD (0.7±0.8) than in patients with AD (0.4±0.6).

Domain-specific assessment

Assessments of patients and caregivers were directly compared in each population for all domains: there was a difference (reflecting patients’ loss of awareness) for most domains, except for word finding (mean rating 2.0 versus 2.1), calculation (1.7 versus 1.9) and affect (1.6 versus 1.7) in the AD population, and for affect (1.7 versus 2.0) in the FTD group.

FTD caregivers reported greater problems in language fluency, word finding, behaviour and daily activities than AD caregivers, whereas AD caregivers reported more memory impairment (effectively observed on neuropsychological tests in table 1). When patients’ assessments were directly compared, patients with AD reported more difficulties in temporal orientation, memory and calculation than patients with FTD.

Discrepancy scores were calculated for each domain by subtracting the self-assessment of the patient from the evaluation of the caregiver. All discrepancy scores showed mean positive values (from 0.03±1.09 to 1.34±1.42) in both patient groups, as caregivers frequently judged the impairments to be higher than did patients (fig 1). There were mild differences between groups, showing that discrepancy scores (anosognosia) were relatively higher in patients with FTD than in patients with AD for speech fluency, word finding and executive abilities, and for changes in behaviour and daily activities.

Figure 1 Mean discrepancy scores for Alzheimer’s disease (AD) and frontotemporal dementia (FTD) in different domains. Between-group differences, *p<0.05.

Multiple regression analysis

The result of the regression analysis was significant {F(12,28) = 3.27, R2 = 0.58, p<0.005}. The discrepancy score (a measure of anosognosia) for cognitive impairment in patients with FTD was positively related to the total Instrumental Activities of Daily Living (IADL) score and to the Neuropsychiatric Inventory (NPI) apathy score (more than to neuropsychological performances).

DISCUSSION

From a methodological viewpoint, the samples of patients with AD and FTD were matched for age, education, disease duration and disease severity. There was a significant difference in Mini Mental State Exam scores, known to more specifically target cognitive impairment of patients with AD. Expectedly, both patients and caregivers reported more memory difficulties in the AD than in the FTD group,19 and caregivers reported significantly more behavioural changes in patients with FTD than in patients with AD on our questionnaire.20 21

The method used to measure unawareness with a research questionnaire was previously described.5 7 The caregiver’s mean evaluation in AD was previously shown to be predicted by variables such as the IADL score and the NPI apathy score.7 The mean evaluation of patients with AD was previously demonstrated to be predicted by scores on the Hamilton depression scale, semantic fluency and delayed recall at California Verbal Learning Test.7 The discrepancy score was partly explained by IADL and apathy, suggesting that lack of motivation and unconcern do participate in unawareness of cognitive impairment in AD.7

According to our results, demented patients showed unawareness for most clinical domains, even at an early stage of the disease.5 This means that patients reported significantly less difficulties than did caregivers. Loss of personal awareness and progressive reduction of speech participate in the prediction of FTD (versus AD) diagnosis.11 Accordingly, caregivers reported more language impairments in patients with FTD than those with AD, and awareness of language problems was significantly lower in patients with FTD than in those with AD. On the contrary, unawareness was not different between groups for domains such as memory, spatial and temporal orientation, attention or abstraction.

Awareness of changes in affect (depressive mood, irritability) was preserved in patients with AD and FTD. The results in AD are in keeping with the report that feelings of depression predict a greater awareness of cognitive dysfunction in patients with AD.7 Of note is that a change in affect was considered as mild by both patients with FTD and their caregiver. On the contrary, both patients with AD and those with FTD lacked awareness of their behavioural changes, and unawareness was significantly more important in patients with FTD. Anosognosia for abnormal behaviour has previously been reported in FTD patients,4 and unawareness of personality changes was already shown to be greater in individuals with FTD than in those with AD.22 Finally, unawareness of decreased daily activities was observed in both patients with AD and those with FTD, but it was significantly greater in patients with FTD. Caregivers of patients with FTD gave higher rating scores for reduced activities, as previously reported,23 but patients with FTD were particularly unaware of this change.

Finally, a multiple regression analysis performed in FTD patients showed that the discrepancy score for cognitive impairment was positively related to the IADL and NPI apathy scores, as previously observed in AD.7 This means that in both diseases, anosognosia for cognitive difficulties was essentially linked to impaired daily functioning and to lack of interest and initiative (more than to cognitive performances). We also searched for correlations between brain glucose metabolism and the discrepancy score, but we failed to identify any cerebral substrate for anosognosia in our FTD population.

In conclusion, assessment obtained in a huge sample of caregivers of patients with FTD and AD using questionnaires provided information about differential diagnosis that was consistent with the literature: predominant impairment of behaviour and reduction of speech characterised patients with FTD, whereas memory impairment was prominent in patients with AD. We observed qualitative and quantitative differences in unawareness between patients with FTD and those with AD, and existing differences showed a greater loss of awareness in the patients with FTD. More research is needed to understand the mechanism of anosognosia in dementia.24

Acknowledgments

This study was conducted on behalf of the Network for Efficiency and Standardization of Dementia Diagnosis (NEST-DD), supported by the European Commission (5th framework), and it was finalised under the auspices of the EC-FP6-project DiMI, LSHB-CT-2005-512146. The work in Liège was supported by grants from the FNRS, IUAP P5/04, the CHU Liège and the University of Liège. FC is a researcher at FNRS.

Footnotes

REFERENCES

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