Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis.

OBJECTIVE: The precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be an oversimplification. Direct comparisons between patients who have behavioural variant FTD (bvFTD) with and without ALS are rare. This prospective comparative study aimed to determine whether there are phenotypic differences in cognition and behaviour between patients with FTD-ALS and bvFTD alone. METHODS: Patients with bvFTD or FTD-ALS and healthy controls underwent neuropsychological testing, focusing on language, executive functions and social cognition. Behavioural change was measured through caregiver interview. Blood samples were screened for known FTD genes. RESULTS: 23 bvFTD, 20 FTD-ALS and 30 controls participated. On cognitive tests, highly significant differences were elicited between patients and controls, confirming the tests' sensitivities to FTD. bvFTD and FTD-ALS groups performed similarly, although with slightly greater difficulty in patients with ALS-FTD on category fluency and a sentence-ordering task that assesses grammar production. Patients with bvFTD demonstrated more widespread behavioural change, with more frequent disinhibition, impulsivity, loss of empathy and repetitive behaviours. Behaviour in FTD-ALS was dominated by apathy. The C9ORF72 repeat expansion was associated with poorer performance on language-related tasks. CONCLUSIONS: Differences were elicited in cognition and behaviour between bvFTD and FTD-ALS, and patients carrying the C9ORF72 repeat expansion. The findings, which raise the possibility of phenotypic variation between bvFTD and FTD-ALS, have clinical implications for early detection of FTD-ALS and theoretical implications for the nature of the relationship between FTD and ALS.

Differential diagnosis of Alzheimer's disease using spectrochemical analysis of blood.

The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer's disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOE ε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson's disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.

Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

OBJECTIVE: To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. BACKGROUND: Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. METHODS: Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. RESULTS: Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. CONCLUSIONS: Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd.

Do NIA-AA criteria distinguish Alzheimer's disease from frontotemporal dementia?

BACKGROUND: Clinical criteria are important for improving diagnostic accuracy and ensuring comparability of patient cohorts in research studies. OBJECTIVE: The aim was to assess the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer's disease (AD) dementia in AD and frontotemporal lobar degeneration (FTLD). METHODS: Two hundred twelve consecutive patients with pathologically confirmed AD or FTLD who were clinically assessed in a specialist cognitive unit were identified. Fifty-five patients were excluded predominantly because of insufficient clinical information. Anonymized clinical data were rated against the NIA-AA criteria by raters who were blinded to clinical and pathologic diagnosis. RESULTS: The NIA-AA AD dementia criteria had a sensitivity of 65.6% for probable and 79.5% for possible AD and a specificity of 95.2% and 94.0% for probable and possible, respectively. CONCLUSION: In patients with FTLD and predominantly early-onset AD, the NIA-AA AD dementia criteria have high specificity but lower sensitivity. The high specificity is due to the broad exclusion criteria.

Sporadic Creutzfeldt-Jakob disease presenting as progressive nonfluent aphasia with speech apraxia.

Progressive non-fluent aphasia (PNFA) is typically associated with pathological changes consistent with frontotemporal lobar degeneration. A 65-year-old male presented with effortful speech, markedly impaired naming and features of speech apraxia, consistent with PNFA. Perceptuospatial function, calculation and executive function were intact. Brain SPECT showed left perisylvian hypoperfusion. He deteriorated profoundly over the subsequent eight months, with appearances on diffusion-weighted magnetic resonance imaging typical of sporadic Creutzfeldt-Jakob disease, which was confirmed pathologically at postmortem examination. While the presence of PNFA with speech apraxia is thought to predict underlying tauopathy, sporadic Creutzfeldt-Jakob disease may mimic this presentation and present in a highly circumscribed form not previously described.

Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations.

The identification of a hexanucleotide repeat expansion in the C9ORF72 gene as the cause of chromosome 9-linked frontotemporal dementia and motor neuron disease offers the opportunity for greater understanding of the relationship between these disorders and other clinical forms of frontotemporal lobar degeneration. In this study, we screened a cohort of 398 patients with frontotemporal dementia, progressive non-fluent aphasia, semantic dementia or mixture of these syndromes for mutations in the C9ORF72 gene. Motor neuron disease was present in 55 patients (14%). We identified 32 patients with C9ORF72 mutations, representing 8% of the cohort. The patients' clinical phenotype at presentation varied: nine patients had frontotemporal dementia with motor neuron disease, 19 had frontotemporal dementia alone, one had mixed semantic dementia with frontal features and three had progressive non-fluent aphasia. There was, as expected, a significant association between C9ORF72 mutations and presence of motor neuron disease. Nevertheless, 46 patients, including 22 familial, had motor neuron disease but no mutation in C9ORF72. Thirty-eight per cent of the patients with C9ORF72 mutations presented with psychosis, with a further 28% exhibiting paranoid, deluded or irrational thinking, whereas <4% of non-mutation bearers presented similarly. The presence of psychosis dramatically increased the odds that patients carried the mutation. Mutation bearers showed a low incidence of motor stereotypies, and relatively high incidence of complex repetitive behaviours, largely linked to patients' delusions. They also showed a lower incidence of acquired sweet food preference than patients without C9ORF72 mutations. Post-mortem pathology in five patients revealed transactive response DNA-binding protein 43 pathology, type A in one patient and type B in three. However, one patient had corticobasal degeneration pathology. The findings indicate that C9ORF72 mutations cause some but not all cases of frontotemporal dementia with motor neuron disease. Other mutations remain to be discovered. C9ORF72 mutations are associated with variable clinical presentations and pathology. Nevertheless, the findings highlight a powerful association between C9ORF72 mutations and psychosis and suggest that the behavioural characteristics of patients with C9ORF72 mutations are qualitatively distinct. Mutations in the C9ORF72 gene may be a major cause not only of frontotemporal dementia with motor neuron disease but also of late onset psychosis.

The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships.

Accuracy of clinical diagnosis of dementia is increasingly important for therapeutic and scientific investigations. In this study, we examine diagnostic accuracy in a consecutive series of 228 patients referred to a specialist early-onset dementia clinic, whose brains were subsequently examined at post-mortem. Diagnosis was based on structured history, neurological examination and neuropsychological assessment, with emphasis on qualitative as well as quantitative aspects of performance. Neuroimaging provided support for but did not alter the clinical diagnosis. We set out the principles that guided diagnosis: (i) time course of illness; (ii) weighting of physical, behavioural and cognitive symptoms and signs; (iii) 'anterior' versus 'posterior' hemisphere character of cognitive change; and (iv) specificity of deficit, paying attention to the differentiation between syndromes of frontotemporal lobar degeneration and focal forms of Alzheimer's disease. Forty-two per cent of the patients had clinical diagnoses of one of the syndromes of frontotemporal lobar degeneration, the high proportion reflecting the research interests of the group. Forty-six per cent were diagnosed with Alzheimer's disease and the remaining patients, dementia with Lewy bodies, Creutzfeldt-Jakob disease, vascular or unclassified dementia. Frontotemporal lobar degeneration was identified with 100% sensitivity and 97% specificity and Alzheimer's disease with 97% sensitivity and 100% specificity. Patients with other pathologies were accurately identified on clinical grounds. Examination of subsyndromes of frontotemporal lobar degeneration showed a relatively predictable relationship between clinical diagnosis and pathological subtype. Whereas the behavioural disorder of frontotemporal dementia was associated with tau, transactive response DNA binding protein 43 and fused-in-sarcoma pathology, cases of frontotemporal dementia with motoneuron disease, semantic dementia and, with one exception, progressive non-fluent aphasia were associated with transactive response DNA binding protein 43 pathology, distinguished by ubiquitin subtyping (types B, C and A, respectively). Clinical diagnoses of progressive apraxia, corticobasal degeneration and progressive supranuclear palsy were, with one exception, associated with Pick, corticobasal and progressive supranuclear palsy subtypes of tau pathology, respectively. Unanticipated findings included Alzheimer pathology in two patients presenting with the behavioural syndrome of frontotemporal dementia and corticobasal pathology in four others with clinical frontotemporal dementia. Notwithstanding such anomalies, which serve as a reminder that there is not an absolute concordance between clinical phenotype and underlying pathology, the findings show that dementias can be distinguished in life with a high level of accuracy. Moreover, careful clinical phenotyping allows prediction of histopathological subtype of frontotemporal lobar degeneration. The principles guiding diagnosis provide the foundation for future prospective studies.

The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) in frontotemporal dementia.

OBJECTIVES: To examine the usefulness of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS) as a cognitive screening tool for the detection of behavioral variant frontotemporal dementia (bvFTD). A secondary aim was to determine whether people with FTD combined with ALS (ALS-FTD) exhibit a similar ECAS profile to that of people with bvFTD alone. Methods: Patients with ALS-FTD and bvFTD and healthy controls were recruited. Participants were administered the ECAS, which comprises tests of language, verbal fluency, executive functions, memory, and visual-spatial functions. They also carried out analogous, full-length cognitive tests that examine naming, spelling, sentence completion, and social cognition skills. Results: The study cohort comprised 20 ALS-FTD patients, 23 with bvFTD, and 30 controls. Highly significant group differences were elicited for all cognitive domains, reflecting poorer performance in patients compared to controls. No significant differences in overall test scores were found between ALS-FTD and bvFTD patients, although ALS-FTD patients showed a higher frequency of impairment on verbal fluency. Correlative analyses revealed inter-relationships in patients (but not controls) between scores in different domains, most marked in bvFTD. There were strong correlations between performance on ECAS subtests and analogous cognitive tasks. Conclusion: The ECAS is a sensitive and valuable tool for the assessment of FTD. Executive, language and behavioral breakdown may, however, compromise performance in other cognitive domains, reducing the specificity of the 'frontotemporal' cognitive profile. Subtle differences observed between ALS-FTD and bvFTD raise questions regarding the precise relationship between bvFTD with and without ALS.

Recent origin and spread of a common Welsh MAPT splice mutation causing frontotemporal lobar degeneration.

IVS10+16C>T is the most prevalent mutation in the microtubule-associated protein tau gene (MAPT) causing frontotemporal lobar degeneration (FTLD) in populations of British descent. A highly conserved 17q21 haplotype was identified in IVS10+16C>T chromosomes from North Wales, Greater Manchester and the London areas of the UK, Australia, and the USA, suggesting the occurrence of a common founder effect. To test this hypothesis, the age of the mutation was estimated by parametric and Bayesian analysis of linkage disequilibrium's decay over generations, and the results were compared with historical and geographical data on FTLD families. The inferred age (23 generations; 95% confidence interval, 9-74 generations) dates the most recent common ancestor of IVS10+16C>T chromosomes before Welsh people started emigrating to the USA and Australia, where they introduced the mutation. The identification of a cohort of FTLD families with a homogeneous genetic background within and around the MAPT locus will further the investigation of the different clinical and pathological presentations of patients with identical MAPT mutations.

Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations.

Two hundred and twenty-three consecutive patients fulfilling clinical diagnostic criteria for frontotemporal lobar degeneration (FTLD), and 259 patients with motor neuron disease (MND), for whom genomic DNA was available, were investigated for the presence of mutations in tau (MAPT) and progranulin (PGRN) genes. All FTLD patients had undergone longitudinal neuropsychological and clinical assessment, and in 44 cases, the diagnosis had been pathologically confirmed at post-mortem. Six different PGRN mutations were found in 13 (6%) patients with FTLD. Four apparently unrelated patients shared exon Q415X 10 stop codon mutation. However, genotyping data revealed all four patients shared common alleles of 15 SNPs from rs708386 to rs5848, defining a 45.8-kb haplotype containing the whole PGRN gene, suggesting they are related. Three patients shared exon 11 R493X stop codon mutation. Four patients shared exon 10 V452WfsX38 frameshift mutation. Two of these patients were siblings, though not apparently related to the other patients who in turn appeared unrelated. One patient had exon 1 C31LfsX34 frameshift mutation, one had exon 4 Q130SfsX130 frameshift mutation and one had exon 10 Q468X stop codon mutation. In addition, two non-synonymous changes were detected: G168S change in exon 5 was found in a single patient, with no family history, who showed a mixed FTLD/MND picture and A324T change in exon 9 was found in two cases; one case of frontotemporal dementia (FTD) with a sister with FTD+MND and the other in a case of progressive non-fluent aphasia (PNFA) without any apparent family history. MAPT mutations were found in 17 (8%) patients. One patient bore exon 10 + 13 splice mutation, and 16 patients bore exon 10 + 16 splice mutation. When PGRN and MAPT mutation carriers were excluded, there were no significant differences in either the allele or genotype frequencies, or haplotype frequencies, between the FTLD cohort as a whole, or for any clinical diagnostic FTLD subgroup, and 286 controls or between MND cases and controls. However, possession of the A allele of SNP rs9897526, in intron 4 of PGRN, delayed mean age at onset by approximately 4 years. Patients with PGRN and MAPT mutations did not differ significantly from other FTLD cases in terms of gender distribution or total duration of illness. However, a family history of dementia in a first-degree relative was invariably present in MAPT cases, but not always so in PGRN cases. Onset of illness was earlier in MAPT cases compared to PGRN and other FTLD cases. PNFA, combined with limb apraxia was significantly more common in PGRN mutation cases than other FTLD cases. By contrast, the behavioural disorder of FTD combined with semantic impairment was a strong predictor of MAPT mutations. These findings complement recent clinico-pathological findings in suggesting identifiable associations between clinical phenotype and genotype in FTLD.

Naming and conceptual understanding in frontotemporal dementia.

Behavioural variant frontotemporal dementia (bvFTD) is characterised by behaviour change and impaired executive skills. There is growing evidence that naming difficulties may also be present but the basis for these is unclear. A primary semantic deficit has been proposed, although executive contributions to naming breakdown are also possible. The study aimed to improve understanding of the naming disorder in bvFTD through direct comparison with semantic dementia (SD), and examination of neural correlates. It aimed also to address current controversies about the role of the anterior temporal lobes in semantic memory. We studied 71 bvFTD and 32 SD patients. Naming data were elicited by two picture naming tests (one challenging and one less demanding) and word comprehension by word-picture matching. Structural magnetic resonance images were rated blind using a standardised visual rating scale. Around half of bvFTD patients showed impaired naming and 17% impaired word-picture matching. Deficits in bvFTD were less severe than in SD, but showed a similar pattern. There were strong inverse correlations between naming scores and atrophy in temporal structures, particularly temporal pole and fusiform gyrus. Word comprehension scores correlated more strongly with posterior than anterior temporal lobe atrophy in SD. Error analysis highlighted a significant relationship in both groups between associative-type responses and temporal pole atrophy. By contrast, 'don't know' responses, suggesting a loss of conceptual knowledge, correlated with more posterior temporal regions. There was some correlation in bvFTD between naming and executive test performance but not with frontal lobe atrophy. The findings support the view that naming problems can arise in bvFTD independently of patients' 'frontal' executive impairment and highlight clinical overlap between bvFTD and SD. We discuss the findings in relation to the hub and spoke model of semantic memory and argue against the notion of an anterior temporal lobe semantic hub.

Semantic dementia and the left and right temporal lobes.

Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study addressed areas of contention: the relative roles of the left and right temporal lobe, the contribution of anterior versus posterior temporal cortex and the status of the anterior temporal lobes as amodal hub. Naming and word comprehension was examined in 41 semantic dementia patients, 31 with left-predominant and 10 right-predominant atrophy. In keeping with expectation, naming and comprehension were significantly poorer in left-predominant patients. Structural magnetic resonance image analysis, using a visual rating scale, showed strong inverse correlations between naming scores and severity of both left anterior and posterior temporal lobe atrophy. By contrast, comprehension performance was more strongly correlated with left posterior temporal atrophy. Analysis of naming errors revealed a correlation between anterior temporal atrophy and associative/functional descriptive responses, implying availability of semantic information. By contrast, 'don't know' responses, indicative of loss of semantic knowledge, were linked to left posterior temporal lobe atrophy. Semantic errors, the hallmark of semantic dementia, were linked to right hemisphere atrophy, especially the right posterior temporal lobe. Matched visual-verbal tasks (famous face and name identification, Pyramids and Palm trees pictures and words, animal knowledge from 3-D models and animal names) administered to nine patients elicited variable correspondence between performance on nonverbal and verbal versions of the task. Marked performance dissociations were demonstrated in some patients: poorer understanding of names/words in left-predominant patients and of faces/pictures/models in right-predominant cases. The findings are compatible with the notion of the anterior temporal lobes as areas of convergence, but are less easily accommodated within the framework of amodal conceptual representation. The data, which reconcile some apparent contradictions in the literature, are discussed in the light of the nature and distribution of degenerative change in semantic dementia.

Cognitive phenotypes in Alzheimer's disease and genetic risk.

Variation in the clinical characteristics of patients with Alzheimer's disease (AD) is increasingly recognised, although the factors underlying variation are not fully understood. The study examined the cognitive characteristics of 523 AD patients at the time of their presentation to a neurological dementia clinic and explored the relationship to family history and apolipoprotein E (APOE) genotype. Distinct profiles were identified, which were mirrored by topographical differences on neuroimaging. Clinical distinctions were maintained over time. Two-thirds of patients showed a constellation of deficits at presentation which included memory, language, visuospatial and constructional difficulties. However, a quarter had circumscribed presentations of amnesia, aphasia, perceptuospatial disorder or apraxia. The rare presence of frontal lobe characteristics was associated with a younger age of onset, an increased incidence of myoclonus at presentation, a positive family history but not with possession of APOE epsilon4 allele. An amnestic presentation (severe, yet circumscribed amnesia) was strongly associated with an older age of onset, a positive family history and the presence of APOE epsilon4 allele. Posterior cortical presentations showed a female bias, were typically sporadic, and showed no association with APOE epsilon4. The findings support the notion of phenotypic variation in AD, and show that genetic risk factors can influence clinical presentation. The findings draw attention to the specific association between APOE epsilon4 allele and memory but challenge the commonly held notion that the presence of the epsilon4 allele inevitably reduces onset age. The findings indicate that risk factors other than APOE epsilon4 allele underlie the non-familial, early onset posterior hemisphere presentations of AD.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

BACKGROUND/OBJECTIVES: We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. METHODS: Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA) criteria and 1998 FTLD criteria. RESULTS: Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited 'early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, 'executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. CONCLUSION: Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

Cognitive-behavioural features of progressive supranuclear palsy syndrome overlap with frontotemporal dementia.

Cognitive impairment is common in patients with the neurodegenerative tauopathy progressive supranuclear palsy (PSP). Although a pattern of 'subcortical' cognitive impairment is considered prototypical in PSP, pathological and clinical observations suggest an overlap with frontotemporal dementia (FTD). Our objective was to evaluate behavioural and cognitive symptoms in a retrospective study of patients with PSP syndrome (PSPS) and their relationship to features seen in behavioural variant FTD. We reviewed the records of 62 patients (29 male, 33 female, median age 65.5 years) evaluated at a tertiary cognitive clinic who met NINDS-SPSP criteria for probable or possible PSP, and collected clinical details of their presenting history, cognitive and behavioural features. We also evaluated the proportion of patients fulfilling FTD Consensus criteria. Cognitive and behavioural symptoms were a predominant presenting feature in 58% of patients evaluated. Cognitive slowing, executive impairments, and inefficient memory recall, consistent with 'subcortical' impairment, were identified in the majority of patients. Twenty patients (32%) fulfilled cognitive and behavioural criteria for possible FTD at initial assessment, whereas behavioural changes not meeting formal diagnostic criteria were present in a greater proportion of the patients. Our findings support the existence of a spectrum of cognitive-behavioural features in PSPS, with significant clinical overlap with behavioural variant FTD. Cognitive and behavioural profiling should be an integral part of the assessment of patients with PSPS.

18F-florbetapir PET in patients with frontotemporal dementia and Alzheimer disease.

UNLABELLED: Pathologic deposition of amyloid ß (Aß) protein is a key component in the pathogenesis of Alzheimer disease (AD) but not a feature of frontotemporal dementia (FTD). PET ligands for Aß protein are increasingly used in diagnosis and research of dementia syndromes. Here, we report a PET study using (18)F-florbetapir in healthy controls and patients with AD and FTD. METHODS: Ten healthy controls (mean age ± SD, 62.5 ± 5.2 y), 10 AD patients (mean age ± SD, 62.6 ± 4.5), and 8 FTD patients (mean age ± SD, 62.5 ± 9.6) were recruited to the study. All patients underwent detailed clinical and neuropsychologic assessment and T1-weighted MR imaging and were genotyped for apolipoprotein E status. All participants underwent dynamic (18)F-florbetapir PET on a high-resolution research tomograph, and FTD patients also underwent (18)F-FDG PET scans. Standardized uptake value ratios (SUVRs) were extracted for predefined gray and white matter regions of interest using cerebellar gray matter as a reference region. Static PET images were evaluated by trained raters masked to clinical status and regional analysis. RESULTS: Total cortical gray matter (18)F-florbetapir uptake values were significantly higher in AD patients (median SUVR, 1.73) than FTD patients (SUVR, 1.13, P = 0.002) and controls (SUVR, 1.26, P = 0.04). (18)F-Florbetapir uptake was also higher in AD patients than FTD patients and controls in the frontal, parietal, occipital, and cingulate cortices and in the central subcortical regions. Only 1 FTD patient (homozygous for apolipoprotein E ε4) displayed high cortical (18)F-florbetapir retention, whereas (18)F-FDG PET demonstrated mesiofrontal hypometabolism consistent with the clinical diagnosis of FTD. Most visual raters classified 1 control (10%) and 8 AD (80%) and 2 FTD (25%) patients as amyloid-positive, whereas ratings were tied in another 2 FTD patients and 1 healthy control. CONCLUSION: Cortical (18)F-florbetapir uptake is low in most FTD patients, providing good discrimination from AD. However, visual rating of FTD scans was challenging, with a higher rate of discordance between interpreters than in AD and control subjects.