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J Neurol (2005) 252 : 1238–1244 DOI 10.1007/s00415-005-0849-1
Roberta Perri Giacomo Koch Giovanni A. Carlesimo Laura Serra Lucia Fadda Patrizio Pasqualetti Carla Pettenati Carlo Caltagirone
■ Abstract The aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to
Received: 18 October 2004 Received in revised form: 22 December 2004 Accepted: 31 December 2004 Published online: 23 May 2005 R. Perri () · G. Koch · G. A. Carlesimo · L. Serra · L. Fadda · C. Caltagirone Fondazione IRCCS Santa Lucia Via Ardeatina, 306 00179 Roma, Italy Tel.: +39-06/51501-574 Fax: +39-06/51501-388 E-Mail:
[email protected] G. A. Carlesimo · L. Fadda · C. Caltagirone University Tor Vergata Rome, Italy P. Pasqualetti AFaR, Ospedale Fatebenefratelli Isola Tiberina Rome, Italy C. Pettenati Centro Regionale Alzheimer, UOC Neurologia Ospedale Rho-Passirana Rho, Italy
ORIGINAL COMMUNICATION
Alzheimer’s disease and frontal variant of frontotemporal dementia A very brief battery for cognitive and behavioural distinction
discriminate between frontotemporal dementia (fv-FTD) and Alzheimer’s disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv-FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Rey’s Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv-FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Rey’s Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants be-
JON 1849
Introduction The frontal variant of frontotemporal dementia (fvFTD) is the most common clinical manifestation of frontotemporal lobe degeneration (FTD), the second
tween fv-FTD and AD patients. The final equation assigned 73.7 % of the fv-FTD patients and 94.7 % of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv-FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8 %) of the diagnostic equation in assigning fv-FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy. ■ Key words Alzheimer’s disease · frontotemporal dementia · differential diagnosis
cause of cortical dementia in the elderly after Alzheimer’s disease (AD) [5, 43]. The initial symptoms in fv-FTD patients usually include progressive personality and social conduct changes coupled with executive functions deficits. The syndrome is associated with predominantly orbitobasal and dorsolateral frontal atrophy
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[45]. Differently, progressive non-fluent aphasia and semantic dementia syndromes, clinical variants of FTD, are associated respectively with the involvement of left perisylvian and left (or bilateral) anterior temporal cortex [19, 38, 45]. The Lund and Manchester Groups’ clinical criteria [51] permit diagnosing fv-FTD with high accuracy [29, 36]. However, many fv-FTD patients also meet the clinical criteria for AD [31, 32, 52] and are often diagnosed as having this pathology [27, 29, 34]. Although the early and profound memory deficit coupled with visuospatial, language and praxis skill impairments in AD contrast with the early dysexecutive syndrome without amnesia typical of fv-FTD, the role of neuropsychological evaluation in distinguishing between these two pathologies is unclear. Some studies demonstrate differences while others show large overlaps in the neuropsychological performance of FTD and AD patients [1, 16, 18, 22, 24, 32, 39, 41]. It has been argued that the discrepant data in literature may be related to several factors. These include imprecise diagnosis, particularly to the mixing of temporal and frontal cases in FTD samples [18, 40, 42], to inadequate neuropsychological test selection and to heterogeneity of the degree of patients’ dementia severity across studies [48]. However, recent studies demonstrate that brief neuropsychological batteries based on the most discriminating cognitive tests (such as memory, verbal fluency, visuo-perceptual and praxis ability tasks), may be useful for making differential diagnoses between fv-FTD and AD [10, 30, 48, 49]. The wide range of non-cognitive behavioural symptoms is the core of clinical feature of fv-FTD [5, 38] and represents the critical clinical marker for its differential diagnosis from AD.Recently,a few studies systematically investigated the prevalence and the specificity of behavioural abnormalities in differentiating FTD from AD [3, 23, 25, 26, 33, 47].Although many behavioural symptoms are present in both disorders, striking differences are documented between FTD and AD. Apathy, disinhibition, euphoria, aberrant motor behaviour [26, 27], stereotypic and eating disorders or loss of social awareness [3, 21] prevail in FTD, while depression is prevalently associated with AD [26]. Discriminant analyses performed in some of these studies demonstrate that detecting this class of behavioural symptoms could greatly facilitate the distinction between fv-FTD and AD [3,26,47].Recently,a retrospective study in which the diagnoses were confirmed at autopsy, showed that social conduct and eating disorders, akinesia, absence of amnesia and perceptual disorders distinguished fv-FTD from AD patients with very high sensitivity and specificity. These findings demonstrate that the combined investigation of behavioural and neuropsychological symptoms could be a very accurate approach for discriminating between the two pathologies [46]. The aim of this study was to investigate whether a
brief neuropsychological battery, consisting of a very limited number of cognitive tests and an evaluation of the behavioural domains known to discriminate most between fv-FTD and AD, might constitute a reliable and practical instrument for making a differential clinical diagnosis between these two pathologies.
Exploratory study ■ Methods Subjects Fifty-eight patients participated in this study. All subjects were recruited through the Foundation IRCCS Santa Lucia of Rome where they were frequenting an Alzheimer’s disease unit as outpatients. The investigative staff consisted of two expert neurologists who were particularly interested in this field, and of neuropsychologists and psychologists. Thirty-nine patients (16 males and 23 females) met the clinical criteria established by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association [31] for probable Alzheimer’s disease. All patients showed the typical Alzheimer symptoms (insidious onset, predominant and progressive memory deficit coupled with disorientation, language and visuospatial disorders) and CT or MRI examination showed diffused cortical atrophy with prevalent involvement of the medial temporal lobes [37]. Because the presently reported neuropsychological investigation was made at the time of first diagnostic evaluation, only two AD patients were under treatment with anticholinesterase drugs. Nineteen patients were diagnosed as fv-FTD on the basis of Neary et al.’s criteria [38] and the revised version of the Lund and Manchester groups’ criteria [51] which permit differentiating fv-FTD from the temporal variants of FTD. All patients with fv-FTD presented with an informant-based history of progressive behaviour and personality changes with a loss of social skills. The patients’ families considered memory loss less disturbing than behavioural disorders. All fv-FTD patients showed the characteristic, predominantly frontal atrophy on MRI and anterior cerebral hypoperfusion on SPECT [35]. Exclusion criteria in the recruitment process included the following: focal or extrapyramidal signs on neurological examination; positive history for neurological or psychiatric diseases; focal lesion on CT or MRI scan (minimal diffuse changes or minimal lacunar lesions of white matter were accepted); major medical illness (e. g. cancer, anaemia, thyroid dysfunction, etc). As reported in Table 1, the two groups were comparable for years of education; however, patients with AD were significantly older than patients with fv-FTD. Moreover, although the two groups of patients had a comparable dementia severity, since they were matched on the basis of Clinical Dementia Rating Scale [20] (sample range 0.5–2), the AD group patients had on average a lower Mini Mental State Examination score (MMSE) [11] than the fv-FTD patients. A significantly
Table 1 Exploratory study: mean (and standard deviation) age, education, CDR and MMSE scores of fv-FTD and AD groups
Age (years) Education (years) CDR MMSE
Fv-FTD (12 M; 7 F)
AD (16 M; 23 F)
F
p
60.68 (11.28) 10.15 (2.85) 0.97 (0.50) 23.72 (3.99)
72.23 (7.49) 9.30 (4.66) 1.0 (0.50) 20.30 (3.51)
21.52 0.53 0.074 10.72
< 0.001 0.46 0.75 0.001
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different average MMSE score in groups of AD and fv-FTD patients with otherwise similar severe dementia symptoms has been frequently reported [3, 15] and generally attributed to low sensitivity of MMSE to early frontal dysfunction.
■ Group Comparison Neuropsychological examination
Neuropsychological examination All patients were submitted to a brief neuropsychological battery assessing verbal and visual-spatial memory, executive functions, language and constructional-praxis abilities.For verbal memory we used the Immediate and Delayed Prose Recall test [6] which requires subjects to recall a short story immediately after presentation and after a 20-min interval (two scores were given for immediate and delayed recall according to the number of informative units reported, range 0–8). To assess constructional-praxis abilities and visuo-spatial memory, the freehand copy followed by immediate and delayed (15-min later) memory reproduction of the Rey’s Complex Figure [6, 44] was used (separate scores were given for copying and for immediate and delayed tests according to accuracy in figure reproduction, range 0–36). Executive functions were tested by using the FAS phonological word fluency test [2, 7]. In this test the score is the number of words beginning with F, A and S generated by the subject in 1 minute for each letter. Finally, language was evaluated by the Boston naming test [13, 14]. Behavioural assessment Qualitative characteristics and severity of behavioural symptoms were evaluated by using the Neuropsychiatry Inventory, a widely used instrument specifically devised to assess behavioural disturbances occurring in dementia [9]. The NPI evaluates ten behavioural domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability and aberrant motor behaviour. The score range for each domain is 0–12 (resulting from a rating of both severity and frequency of the behavioural disorder, with 0 corresponding to absence of the behaviour disorder and 12 to maximum severity and frequency of the disorder).
Table 2 Mean scores (and standard deviation) obtained by fv-FTD and AD groups on the neuropsychological battery tests
Results
The mean scores (adjusted for education and age according to published normative data) obtained by the fv-FTD and AD groups on the cognitive tests are reported in Table 2. One-way analysis of variance (ANOVA) was used to compare the mean scores obtained by the two groups. For the Boston naming test (for which Italian normative data are not available) the mean group comparison was covariated for age (ANCOVA). fv-FTD patients performed significantly better than AD patients on both verbal memory tests (Immediate and Delayed Prose Recall), on both visuo-spatial memory tasks (Immediate and Delayed Rey’s Figure Recall) and on the constructional praxis test (Rey’s Figure Copy). Instead, fv-FTD performed significantly worse than AD patients on the FAS phonological word fluency test. No difference emerged between groups on the Boston naming test.
Behavioural assessment The mean scores obtained by the two groups on each NPI sub-scale are reported in Table 3.A two-way ANOVA with Group as between factor and NPI sub-scales as within factor showed that mean total NPI score was significantly higher in the fv-FTD group (1.69) than in the AD group (0.88) (Group effect: F = 9.00, p = 0.004). The significant Group NPI sub-scales interaction (F = 5.27, p < 0.001) suggested a different performance profile of the two groups across the 10 NPI sub-scales. Indeed, as reported in Table 3, post-hoc comparisons showed that fv-FTD patients were significantly more apathetic, disinhibited and euphoric than AD patients.A trend toward
Fv-FTD
AD
F
p
Verbal Memory Immediate Prose Recall Delayed Prose Recall
3.72 (2.08) 3.06 (2.21)
1.8 (2.2) 0.89 (1.62)
10.02 17.85
0.003 < 0.000
Visuo-spatial Memory Rey’s Figure Immediate Recall Rey’s Figure Delayed Recall
8.55 (6.96) 7.08 (6.29)
2.14 (3.92) 1.43 (3.27)
19.30 19.61
< 0.000 < 0.000
Praxis Rey’s Figure Copy
23.85 (7.69)
12.02 (9.49)
20.46
< 0.000
Executive Functions FAS Phonological Fluency
13.87 (7.98)
20.68 (9.7)
7.01
0.01
Language Boston Naming Test
25.62 (3.11)
24.31 (5.31)
0.92
0.34
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Table 3 Mean scores (and standard deviations) obtained by fv-FTD and AD groups on NPI subscales NPI subscales
Fv-FTD
AD
p
Delusions Hallucination Agitation/Aggression Depression/Dysphoria Anxiety Euphoria Apathy Disinhibition Irritability/Lability Aberrant Motor Behaviour
0.36 (0.76) 0.10 (0.45) 0.78 (1.35) 1.78 (2.04) 0.68 (1.24) 2.47 (4.00) 4.36 (3.89) 3.00 (3.04) 1.63 (2.26) 1.73 (3.54)
0.87 (2.11) 0.10 (0.38) 0.74 (1.55) 1.35 (1.67) 1.17 (1.69) 0.23 (0.84) 1.56 (1.84) 0.82 (2.22) 1.07 (1.52) 0.87 (1.83)
0.32 0.99 0.92 0.40 0.33 < 0.000 < 0.000 < 0.000 0.27 0.091
Wilks λ 0.90; canonical coefficient –0.55) and by Apathy as the third step (F to enter 12.66; Wilks λ 0.84; canonical coefficient 0.49). No other variable entered in the analysis. The final equation using these 3 variables accurately assigned 73.7 % of the patients with fv-FTD and 94.7 % of the patients with AD to the correct diagnostic group (87.7 % of the patients correctly classified).
Validation study
significantly higher aberrant motor behaviour score in fv-FTD than in AD patients was also detected. No significant difference between the two groups emerged on the other NPI sub-scales.
Because validation of discriminant analysis by applying the function for classification of the same group used to develop the function or by cross-validating by excluding just one case at a time implies, especially in the first case, an upward bias in the predictive accuracy, statistical handbooks suggest using a holdout sample. If the categorical group sample sizes are unequal, the sizes of the groups selected for the holdout sample should be proportionate to the total sample distribution [17].
■ Discriminant analysis
■ Subjects
A stepwise discriminant analysis was performed to identify the linear combination of neuropsychological and behavioural measures able to best discriminate between AD and fv-FTD patients. For this aim, one test for each of the investigated cognitive domains was selected as follows: memory – Delayed Prose Recall; language – Boston naming test; executive functions – FAS Verbal Fluency; praxis and visuo-spatial abilities – Rey’s Figure A Copy. As for the behavioural symptoms, the results of the present study are in substantial agreement with the three previous studies which also utilised NPI for comparing fv-FTD and AD patients [26, 28, 47]. In particular, all of these studies reported higher scores in the fvFTD than in AD patients in the disinhibition, euphoria and aberrant motor behaviour scales [26, 28, 47]. Two studies also found higher apathy in fv-FTD than in AD patients [26, 28]. Accordingly, the scores obtained on the apathy, euphoria, disinhibition and aberrant motor behaviour scales of the NPI were also selected for the discriminant analysis. Since the statistical units in discriminant analysis were represented by the eight scores (four cognitive tasks and four behavioural scales), a ratio of 7.25 cases (58 patients – 39 AD and 19 fv-FTD) resulted for each variable. This is above the minimum ratio of at least 5 cases per variable usually requested by multiple regression analyses [17]. The stepwise method selected Rey’s Figure A Copy (F to enter 18.98; Wilks λ 0.721; canonical coefficient 0.82) at first step, followed by Verbal Fluency (F to enter 5.02;
We strictly followed these recommendations and gathered a second independent sample of 11 fv-FTD (5 males and 6 females) and 23 AD patients (5 males and 18 females). Recruitment process and clinical criteria followed for these two further experimental samples were the same as those utilised in the Exploratory study. As reported in Table 4, the two groups were comparable for education but, again, AD patients were older than fvFTD patients. As in the exploratory study, AD patients’ MMSE mean score was lower than that of fv-FTD patients, but the two groups had comparable CDR scores (sample range 0.5–2). Furthermore, the validation study AD and fv-FTD groups were comparable with their respective exploratory study groups for age, education, MMSE and CDR mean scores (F consistently < 3.00). Table 4 Validation study: mean (and standard deviation) age, education, CDR and MMSE scores of fv-FTD and AD groups
Age (years) Education (years) CDR MMSE
Fv-FTD (5 M; 6 F)
AD (5 M; 18 F)
F
p
64.27 (9.34) 8.66 (3.84) 1.05 (0.52) 23.79 (5.19)
75.65 (8.01) 7.39 (3.25) 1.13 (0.43) 20.25 (2.54)
13.50 0.89 0.25 7.03
< 0.001 0.35 0.61 0.012
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■ Results The three scores relative to each validation sample patient’s performance on Rey’s Figure A Copy, Verbal Fluency and Apathy were introduced in the diagnostic equation to obtain the probability of each patient belonging to the fv-FTD or AD group.The diagnostic equation accurately assigned 81.8 % of the patients with fvFTD and 82.6 % of the patients with AD to the correct diagnostic group (82.3 % of the patients correctly classified).
Discussion In this study, distinct patterns of cognitive deficits emerged in fv-FTD and AD groups. In particular, consistent with a relatively large body of experimental literature, AD patients performed worse on episodic memory [18, 30, 42] and visuo-spatial tasks [18, 32], while fv-FTD patients had reduced executive functions than AD patients [30]. Instead, no difference was observed between the two groups of patients on a picture naming test [32, 39, 48]. Results of the present study also confirm previous data from the literature regarding the higher prevalence of behavioural symptoms in fv-FTD than in AD patients [3, 26, 47]. In particular, our data agree with findings of previous researches in which NPI was also used to investigate behavioural differences between these two pathologies and confirm the higher prevalence and severity in fv-FTD patients of disinhibition, euphoria, aberrant motor behaviour [26, 28, 47] and apathy [26, 28]. The main focus of the present study was to investigate whether a brief battery combining both neuropsychological and behavioural data might be useful for the differential diagnosis of fv-FTD and AD. For this purpose, a discriminant analysis was performed to identify the subset of cognitive and behavioural indexes that best discriminated patients in the two dementia groups. In this analysis, we used one test score for each cognitive area investigated (memory, constructional-praxis, executive functions and language) and the four subscales of NPI which in the present and previous studies best discriminated fv-FTD and AD samples (apathy, disinhibition, aberrant motor behaviour and euphoria). The analysis selected scores on FAS verbal fluency, Rey’s Figure copy and NPI apathy sub-scale as best discriminating between fv-FTD and AD patients groups. Entering these scores in the discriminant equation permitted assigning 73.7 % of the fv-FTD patients and 94.7 % of the AD patients to the correct group.A successive validation study confirmed the high reliability of the discriminant equation in correctly assigning AD and fv-FTD patients. Indeed, in a new independent sample of 11 fv-FTD and
22 AD patients the diagnostic sensitivity and specificity of the equation was 82.6 % and 81.8 % respectively. The observation that verbal fluency and constructional praxis scores were the cognitive indexes that most reliably discriminated between AD and fv-FTD patients probably reflects the different distribution of pathological changes in these two disorders. FTD is characterised by a pathological involvement of the pre-frontal and anterior temporal lobe and, unlike AD, FTD tends to spare occipito-parietal cortical regions [46]. In contrast, the cortical atrophy in AD mainly affects the medial temporal lobe and involves prefrontal regions relatively late in the course of illness [4]. Accordingly, studies with single photon emission computed tomography revealed that patients with FTD present a hypometabolism in the frontal region while AD patients present with a typical pattern of fixation defect in the temporo-parietal-occipital cortex [8]. The progressive personality changes characteristic of fv-FTD have been related to the involvement of a neural network formed by the ventral frontal lobe, temporal pole and amygdala [3]. However, two contrasting behavioural subsyndromes have been described in fv-FTD: the first, characterised by disinhibition, distractibility and purposeless overactivity has been associated with atrophy changes at the level of the orbital frontal and temporal pole cortex; instead, apathy, inertia and loss of volition prevail when atrophy mainly extends to the dorsolateral prefrontal cortex [50]. Our data are consistent with this view insofar as the two most distinctive behavioural traits of the fv-FTD patients were apathy and disinhibition,that is the core of the two syndromes.The fact that the stepwise analysis selected only one of the two main behavioural subsets may be due to a slight prevalence of apathetic fv-FTD patients in our cohort. Although both cognitive and behavioural differences exist between FTD and AD, previous studies aimed at differentiating the two pathologies, considered the two aspects separately and, surprisingly, discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. Recently, however, a retrospective study conducted on FTD and AD patients diagnosed at autopsy showed the importance of both symptom classes for discriminating between the two syndromes [45]. Our results confirm this finding in a clinical setting showing the high discrimination sensitivity and specificity of a battery, which although very brief, combines the most salient cognitive and behavioural differences between the two pathologies. However, both the exploratory and the validation study were conducted on samples of AD patients affected by the typical presentation of the disease, introducing a circularity in the diagnostic process and raising the possibility that if atypical AD patients (in particular cases with prominent executive dysfunctions, see at this regard [12]) were considered, they could be not accurately di-
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agnosed. Furthermore, the importance should be emphasised, in the differential diagnostic process, of taking into account the progression of the earliest patients’ symptoms which are likely to represent the most useful to distinguish between FTD and AD. The results of the present study were derived from a relatively small cohort of patients and need to be repli-
cated in a larger sample population. However, in a clinical context, where the risk of confusing the diagnosis of fv-FTD and AD is well known [43], these results emphasise the importance of rating all core clinical features of the two syndromes as objectively as possible to improve diagnostic accuracy.
References 1. Binetti G, Locascio JJ, Corkin S, Vonsattel JP, Growdon JH (2000) Differences between Pick Disease and Alzheimer disease in clinical appearance and rate of cognitive decline. Arch Neurol 57:225–232 2. Borkowsky JG, Benton AL, Spreen O (1967) Word fluency and brain damage. Neuropsychologia 5:135–140 3. Bozeat S, Gregory CA, Lambon Ralph A, Hodges JR (2000) Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease. J Neurol Neurosurg Psychiatry 69:178–186 4. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Berl) 82:239–259 5. Brun A (1993) Frontal lobe degeneration of non-Alzheimer type revisited. Dement Geriatr Cogn Disord 4: 126–131 6. Carlesimo GA, Buccione I, Fadda L, Graceffa A, Mauri M, Lorusso S, Bevilacqua G, Caltagirone C (2002) Standardizzazione di due test di memoria per uso clinico: Breve Racconto e Figura di Rey. Nuova Rivista di Neurologia 12:1–13 7. Carlesimo GA, Caltagirone C, Gainotti G (1996) The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery. Eur Neurol 36(6):378–384 8. Charpentier P, Lavenu I, Defebvre L, Duhamel A, Lecouffe P, Pasquier F, Steinling M (2000) Alzheimer’s disease and frontotemporal dementia are differentiated by discriminant analysis applied to Tc HmPAO SPECT data. J Neurol Neurosurg Psychiatry 69: 661–663 9. Cummings JL, Mega M, Gray K, Rosemberg-Thompson S, Carusi DA, Gornbein J (1994) The Neuropsychiatry Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44:2308–2314
10. Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a Frontal Assessment Battery at bedside. Neurology 12:1621–1626 11. Folstein MF, Folstein SE, McHigh PR (1975) “Mini Mental State”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198 12. Galton CJ, Patterson K, Xuereb JH, Hodges JR (2000) Atypical and typical presentation of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 123:484–498 13. Goodglass H, Kaplan E (1972) The Boston Diagnostic Aphasia Examination. The assessment of aphasia and related disorders. Lea and Febiger, Philadelphia 14. Goodglass H, Kaplan E (1973) The Boston Diagnostic Aphasia Examination. The assessment of aphasia and related disorders (second ed.). Lea and Febiger, Philadelphia 15. Gregory CA, Hodges JR (1996) Frontotemporal dementia: use of consensus criteria and prevalence of psychiatric features. Neuropsychiat Neuropsychol Behav Neurol 9:937–942 16. Gregory CA, Orrel M, Sahakian B, Hodges JR (1997) Can frontotemporal dementia and Alzheimer’s disease be differentiated using a brief battery of tests? Int J Geriatr Psychiatry 12: 375–383 17. Hair JF, Anderson RE, Tatham RL, Black WC (1998) Multiple discriminant analysis and logistic regression, Chapter in: Multivariate data analysis, Prentice Hall, p 258 18. Hodges JR, Garrard P, Perry R, Patterson K, Ward R, Bak Thomas, Gregory C (1999) The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer’s disease: A comparative neuropsychological study. Neuropsychology 13(1):31–40 19. Hodges JR, Miller B (2001) The classification, genetics and neuropathology of frontotemporal dementia. Introduction to the special topic papers: Part I Neurocase 7:31–35
20. Hughes CP, Berg L, Danziger WL, Coben LA, Martin R (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140:566–572 21. Ikeda M, Brown A, Holland AJ, Fukuhara R, Hodges JR (2002) Changes in appetite, food preference and eating habits in frontotemporal dementia and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 73: 371–376 22. Jagust WJ, Reed BR, Seab JP, Kramer JH, Budinger TF (1989) Clinical-physiologic correlates of Alzheimer’s disease and frontal lobe dementia. Am J Physiol Imaging 4:89–96 23. Kertesz A, Nadkarni N, Davidson W, Thomas AW (2000) The frontal behavioral inventory in the differential diagnosis of frontotemporal dementia. J Int Neuropsychol Soc 6:460–468 24. Kumar A, Shapiro MB, Haxby JV, Grady CL, Friedland RP (1990) Cerebral metabolic and cognitive studies in dementia with frontal lobe behavioural features. J Psychiatr Res 24: 97–109 25. Lebert F, Pasquier F, Souliez L, Petit H (1998) Frontotemporal behavioural scale. Alzheimer Dis Assoc Disord 12(4):335–339 26. Levy ML, Miller BL, Cummings JL, Fairbanks LA, Craig A (1996) Alzheimer’s disease and frontotemporal dementias. Behavioral distinction. Arch Neurol 53:687–690 27. Litvan I, Agid Y, Sastrj N, Jankovic J, Wenning GK, Goetz CG, Verny M, Brandel JP, Jellinger K, Chaudhuri KR, McKee A, Lai EC, Pearce RK, Bartko JJ, Sastrj N (1997) What are the obstacles for an accurate clinical diagnosis of Pick’s disease? A clinicopathologic study. Neurology 49:62–69 28. Liu W, Mille BL, Kramer JH, Rankin K, Wyss-Coray C, Gearhart R, Phengrasamy L, Weiner M, and Rosen HJ (2004) Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 67:742–748
1238_1244_Perri_JON_1849 30.09.2005 07:56 Uhr Seite 1244
1244
29. Lopez OL, Litvan I, Catt KE, Sowe R, Klunk W, Kaufer DI, Becker JT, DeKosky ST (1999) Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementia. Neurology 53:1292–1299 30. Mathuranath PS, Nestor PJ, Berrios GE, Rakovicz W, Hodges JR (2000) A brief cognitive test battery to differentiate Alzheimer’s disease and frontotemporal dementia. Neurology 55:1613–1620 31. McKhann G, Drachman D, Folstein M,, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health Services Task Force on Alzheimer’s disease. Neurology 34:939–944 32. Mendez MF, Cherrier M, Perryman KM, Pachana N, Miller BL, Cummings JL (1996) Frontotemporal dementia versus Alzheimer’s disease: differential cognitive features. Neurology 47: 1189–1194 33. Mendez MF, Perryman KM, Miller BL, Cummings JL (1998) Behavioral differences between frontotemporal dementia and Alzheimer’s disease: a comparison on the BEHAVE-AD rating scale. Int Psychogeriatr 10(2):155–162 34. Mendez MF, Selwood A, Mastri AR, Frey WH (1993) Pick’s disease versus Alzheimer’s disease: a comparison of clinical characteristics. Neurology 43: 289–292 35. Miller BL, Gearhart R (1999) Neuroimaging in the diagnosis of frontotemporal dementia. Dement Geriatr Cogn Disord 10(S):71–74 36. Miller BL, Ikonte C, Ponton M, Levy M, Boone K, Darby A, Berman N, Mena I, Cummings JL (1997) A study of the Lund and Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations. Neurology 48:937–942
37. Nagy Z, Hindley NJ, Braak E, YilmazerHanke DM, Shults C, Barnetson L, King EM, Jobst KA, Smith AD (1999) The progression of Alzheimer’s disease from limbic regions to the neocortex: clinical, radiological and pathological relationships. Dement Geriatr Cogn Disord 10:115–120 38. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman N, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF (1998) Frontotemporal lobe degeneration. A consensus on clinical diagnostic criteria. Neurology 51: 1546–1554 39. Pachana NA, Boone BK, Miller BL, Cummings JL, Berman N (1996) Comparison of neuropsychological functioning in Alzheimer’s disease and frontotemporal dementia. J Int Neuropsychol Soc 2:505–510 40. Pasquier F, Grymonprez L, Lebert F, Van der Linden M (2001) Memory impairment differs in frontotemporal dementia and Alzheimer’s disease. Neurocase 7:161–171 41. Pasquier F, Lebert F, Grymonprez L, Pettit H (1995) Verbal fluency in dementia of frontal lobe type and dementia of Alzheimer type. J Neurol Neurosurg Psychiatry 58:81–84 42. Perry RJ and Hodges JR (2000) Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer’s disease. Neurology 54: 2277–2284 43. Ratnavalli E, Brayne C, Dawson K, Hodges JR (2002) The prevalence of frontotemporal dementia. Neurology 58:1615–1621 44. Rey A (1941) L’examen psychologique dans les cas d’encephalopathie traumatique. Archives de Psychologique 28:286–340
45. Rosen HJ, Gorno-Tempini ML, Goldman WP, Perry RJ, Shuff N, Weiner M, Feiwell R, Kramer JH, Miller BL (2002) Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 58:198–208 46. Rosen HJ, Hartikainen KM, Jagust W, Kramer JH, Reed BR, Cummings JL, Boone K, Ellis W, Miller C, Miller BL (2002) Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD. Neurology 58:1608–1615 47. Rozzini L, Lussignoli G, Padovani A, Bianchetti A, Trabucchi M (1997) Alzheimer’s disease and frontotemporal dementia. Arch Neurol 54:350 48. Siri S, Benaglio I, Frigerio A, Binetti G, Cappa SF (2001) A brief neuropsychological assessment for the differential diagnosis between frontotemporal dementia and Alzheimer’s disease. Eur J Neurol 8:125–132 49. Slachevsky A, Villalpando JM, Sarazin M, Hahn-Barma V, Pillon B, Dubois B (2004) Frontal assessment battery and differential diagnosis of frontotemporal dementia and Alzheimer’s disease. Arch Neurol 61(7):1104–1107 50. Snowden JS, Bathgate D, Varma A, Blackshaw A, Gibbons ZC, Neary D (2001) Distinct behavioural profiles in frontotemporal dementia and semantic dementia. J Neurol Neurosurg Psychiatry 70:323–332 51. The Lund and Manchester Groups. Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57:416–418 52. Varma AR, Snowden JS, Lloyd JJ, Talbot PR, Mann DMA, Neary D (1999) Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry 66:184–188
