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May 14, 2019; 92 (20) Article

Incidence of frontotemporal lobar degeneration in Italy

The Salento-Brescia Registry study

Giancarlo Logroscino, Marco Piccininni, Giuliano Binetti, Chiara Zecca, Rosanna Turrone, Rosa Capozzo, Rosanna Tortelli, Petronilla Battista, Eriola Bagoj, Roberta Barone, Silvia Fostinelli, Luisa Benussi, Roberta Ghidoni, Alessandro Padovani, Stefano F. Cappa, Antonella Alberici, Barbara Borroni
First published April 12, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007498
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Abstract

Objective The goal of the present work, based on a collaborative research registry in Italy (the Salento-Brescia Registry), was to assess the incidence of frontotemporal lobar degeneration (FTLD) and to define the frequencies of different FTLD phenotypes in the general population.

Methods The study was conducted from January 1, 2017, to December 31, 2017, in 2 Italian provinces: Lecce (in Puglia) in the south (area 2,799.07 km2, inhabitants 802,082) and Brescia (in Lombardy) in the north (area 4,785.62 km2, inhabitants 1,262,678). During the study period, all new cases of FTLD (incident FTLD) were counted, and all patients' records were reviewed. The incidence was standardized to the Italian general population in 2017.

Results In the 2 provinces, 63 patients with FTLD were diagnosed. The incidence rate for FTLD was 3.05 (95% confidence interval [CI] 2.34–3.90) per 100,000 person-years (py), while the age-sex standardized incidence rate was 3.09 (95% CI 2.95–3.23) per 100,000 py. In the Italian population, the lifetime risk was 1:400. There was a progressive increase in FTLD incidence across age groups, reaching its peak in the 75- to 79-year-old group, with an incidence rate of 15.97 (95% CI 8.94–26.33) per 100,000 py. The behavioral variant of frontotemporal dementia was the most common phenotype (37%). No difference in crude incidence rate between the 2 provinces was observed.

Conclusion FTLD is a more common form of dementia than previously recognized, with a risk spanning in a wide age range and with maximum incidence in the mid-70s. Improved knowledge of FTLD epidemiology will help to provide appropriate public health service policies.

Glossary

AD=
Alzheimer disease;
bvFTD=
behavioral variant of frontotemporal dementia;
CBS=
corticobasal syndrome;
CDCD=
Centres for Cognitive Disorders and Dementias;
CI=
confidence interval;
DSM-III-R=
Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
FTLD=
frontotemporal lobar degeneration;
GP=
general practitioner;
nfvPPA=
nonfluent variant of primary progressive aphasia;
PSP=
progressive supranuclear palsy;
py=
person-years;
SLAP=
Sclerosi Laterale Amiotrofica–Puglia;
SLAPDem=
Sclerosi Laterale Amiotrofica–Puglia including dementia;
svPPA=
semantic variant of primary progressive aphasia

Frontotemporal lobar degeneration (FTLD) is a focal neurodegenerative disease with progressive atrophy of the frontal and temporal lobes.1,–,3 FTLD includes a wide spectrum of heterogeneous clinical conditions, characterized by social dysfunctions, personality changes, and impairment in language, executive functions, and motor functions.

Revision of clinical criteria over time has prompted a wider recognition of the disease in experienced clinical settings.4,5 Epidemiologic studies assessing the overall FTLD incidence and the relative frequency of the different phenotypes in the general population are scarce, with controversial results.6,–,8 FTLD is a relatively rare disease,9 and epidemiologic studies require surveys of large populations with expensive and complex networks with involvement of specific clinical expertise.10

In FTLD epidemiology, we have identified 2 critical issues. First, FTLD has been considered a presenile dementia with a strong genetic background. It is not clear whether FTLD should be confined exclusively within the early-onset dementias or if it also involves advanced age.11 Second, the distribution of clinical phenotypes in the general population is not known, but estimates are based on clinical series from tertiary centers.

These observations prompted the present study, which was based on the collaboration of 2 registries in Italy, one in the north and one in the south (the Salento-Brescia Registry), with 2 specific aims: to measure the incidence of FTLD in the general population with new diagnostic criteria4,5 and to describe the frequencies of different phenotypes.

Methods

Study population

This study was conducted from January 1, 2017, to December 31, 2017, in 2 Italian provinces: the province of Lecce (in the Salento area, Puglia), located in the south of Italy (area 2,799.07 km2, inhabitants 802,082, male/female ratio 0.92, aging index [ratio of individuals >64 years of age to population <15 years of age] 1.83, individuals ≥65 years of age 23.35%) and the province of Brescia (in Lombardy), located in the north of Italy (area 4,785.62 km2, inhabitants 1,262,678, male/female ratio 0.97, aging index 1.43, population ≥65 years of age 21.00%) (ISTAT data, demo.istat.it) (figure 1 shows the locations of the 2 provinces). During the study period, new cases of FTLD (incident FTLD) were considered, and all patient records were reviewed. No prevalent cases were included (diagnosis before January 1, 2017).

Figure 1
Figure 1 Two sites of the Salento-Brescia Registry study: province of Lecce (south Italy) and province of Brescia (north Italy)

The Salento-Brescia Registry consists of a network including dementia care centers and neurologic and geriatric wards involved in the care of cognitive disorders, including rare dementias, in outpatient clinics of the Italian National Health System. In Italy, every citizen has free access to health care through the National Health System. The referral center in the province of Lecce (Pia Fondazione Cardinale G. Panico, in Tricase) and the 2 referral centers in Brescia (Neurology Unit, University of Brescia, and IRCCS Fatebenefratelli) contacted all the facilities of the 2 provinces periodically. Local lay associations and charities involved in dementia care also were contacted. These referral centers are part of the European FTLD network, which involves 11 centers in Italy and 15 centers in Germany that are specialized in FTLD care and share clinical and neuropsychological assessments and diagnostic protocols (ftld.de).

In the region of Puglia, a disease registry for amyotrophic lateral sclerosis (Sclerosi Laterale Amiotrofica–Puglia [SLAP]) has already been active since 1998. Since 2016, the registry has taken on a new role, including cases of FTLD and other neurodegenerative dementias, to establish an integrated registry called SLAPDem. In the provinces of Lecce and Brescia, the neurologic and geriatric services and the Centres for Cognitive Disorders and Dementias (CDCD) (5 in the province of Lecce and 12 in the province of Brescia), active since 2000 to cover all dementia cases, have been involved in reporting suspected cases of FTLD. Moreover, in the province of Lecce, general practitioners (GPs) were informed of the existence of the registry, and the contact was mainly through public educational meetings. In the province of Brescia, GPs were informed through Continue Educational Programme and meetings sponsored by the Italian Frontotemporal Dementia Association.

Assessment procedures

Patients included in this study fulfilled FTLD diagnosis according to current clinical criteria. In particular, we considered the behavioral variant of frontotemporal dementia (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), semantic variant PPA (svPPA),4,5 or unspecified PPA when the PPA subtype was still unclear.5 We also considered patients with frontotemporal dementia–amyotrophic lateral sclerosis, progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS), based on current criteria.12,13 We did not consider the logopenic variant of PPA because the majority of these cases have Alzheimer disease (AD) pathology.

The present study relied on a 2-step process. The suspected cases of FTLD were first referred by GPs or the CDCD to Brescia or Tricase centers on the basis of symptom onset, an initial clinical and neuropsychological evaluation, and eventually a brain imaging study. The CDCD network allowed complete coverage of all suspected cases of FTLD because, according to the Italian National Health System, all cases of suspected dementia have to be referred to the CDCD. The staff of the CDCD is made up of neurologists or geriatricians with expertise in the field of dementia who are involved primarily in the diagnosis and cure of neurodegenerative dementing disorders.

As a second step, each referred patient with suspected FTLD was then evaluated by the research team using a standardized protocol, carefully recording the demographic characteristics, family history, and clinical features. During the first visit, dementia experts (G.B., A.P., A.A., and B.B. in Brescia; G.L., R.T., and R.C. in Tricase) performed a neurologic, cognitive, and behavioral examination and did a preliminary assessment of eligibility. Eligible patients underwent a standardized neuropsychological evaluation, brain MRI, and, in selected cases, CSF analysis.

In particular, a detailed clinical history was carefully recorded through a structured questionnaire. We considered age at disease onset, disease duration, possible changes in clinical phenotype over time, and the “time of shift” from 1 phenotype to another. The age at onset was defined as the age at which the first symptoms consistent with FTLD were observed by the partner or caregiver. Each patient underwent a clinical evaluation and a standardized extensive neuropsychological assessment, as previously published.14,15 Moreover, patients underwent structural MRI or brain CT scan when MRI was not tolerated or was contraindicated. CSF analyses (tau, phospho-tau and β-amyloid42) were performed to rule out AD. Further functional brain imaging and neurophysiologic examinations were performed when needed.

At the end of the diagnostic workup, on the basis of clinical, neuropsychological, and instrumental data, diagnosis of FTLD might be confirmed and the patient could be included in the study or otherwise excluded. In questionable cases, a further step approach was undertaken; a joint evaluation was carried out, and a shared diagnosis in a team discussion was made. After agreement, the patient could be included if the FTLD diagnosis was confirmed.

Statistical analysis

Categorical variables were reported as frequency and percentage, along with 95% confidence intervals (95% CIs), whereas continuous variables were reported as mean, median, range, and SD.

Individual and pooled general, age-specific, sex-specific, and age-sex–specific incidence rates were computed for the 2 provinces. All rates were calculated using the reference population of the corresponding geographic area on January 1, 2017, as population at risk (source demo.istat.it). Therefore, no variation was assumed during the 12 months of the study period.

Incidence rates of the 2 provinces and of the pooled population were standardized with the age-sex person-time distribution of the general Italian population at January 1, 2017.

Lifetime risk of FTLD was estimated with the current probability method,16 the 2016 Italian life table (demo.istat.it), and the pooled Salento-Brescia Registry age-sex–specific incidence rates.

The Poisson exact method was used to calculate the CIs for rates (confidence level = 0.95).

Differences between the 2 provinces were assessed with the Pearson χ2 test for categorical variables, the Mann-Whitney U test for quantitative variables when distribution was not normal, and the Student t test for quantitative variables with normal distribution. The Shapiro-Wilk test was used to check for normality assumption. Incidence rates were compared by testing the hypothesis that their ratio was equal to one. Statistical significance level was set to 0.05 for all the analyses. Statistical analyses were performed with R (version 3.3.1) and R studio (version 1.0.153, R Foundation for Statistical Computing, Vienna, Austria).

Standard protocol approvals, registrations, and patient consents

The study was approved by the Brescia Hospital Ethics Committee and the ASL Lecce Ethics Committee. Written informed consent was obtained from all participants or their caregivers.

The study was compliant with Strengthening the Reporting of Observational Studies in Epidemiology17 and Standards of Reporting of Neurologic Disorders guideline18 requirements (supplementary material available from Dryad, doi.org/10.5061/dryad.587cv26).

Data availability

Anonymized data will be shared by request from any qualified investigator.

Results

During the study period, 74 individuals with suspicions for FTLD were initially assessed (mean age 71.09 years, female 47.30%, mean education 7.46 years). At the end of diagnostic workup, 11 individuals (14.86%) were excluded: 4 individuals did not fulfill FTLD criteria on the basis of the results of the comprehensive diagnostic workup (n = 2 not fulfilling CBS criteria, n = 1 not fulfilling PSP criteria, n = 1 cerebral large vessel ischemic disease); 5 individuals had CSF AD-like pattern; and 2 completed partially the diagnostic workup, so the available data were not considered sufficient for a diagnosis of FTLD and thus they were not eligible for inclusion in the study (supplementary material available from Dryad, doi.org/10.5061/dryad.587cv26).

Thus, in the 2 provinces, 63 patients with FTLD were diagnosed: bvFTD was diagnosed in 23 (36.51%, 95% CI 24.73%–49.60%) cases, nfvPPA in 19 (30.16%, 95% CI 19.23%–43.02%) cases, CBS in 7 (11.11%, 95% CI 4.59%–21.56%) cases, and PSP in 9 (14.29%, 95% CI 6.75%–25.39%) cases. Two patients (3.17%, 95% CI 0.39%–11.00%) were diagnosed as having frontotemporal dementia–amyotrophic lateral sclerosis, and 3 patients (4.76%, 95% CI 0.99%–13.29%) were diagnosed as having as unspecified PPA subtypes (figure 2). No cases of svPPA were identified. Demographic and clinical characteristics of included patients with FTLD are reported in table 1.

Figure 2
Figure 2 Distribution of incident cases by frontotemporal lobar degeneration phenotype in Lecce and Brescia provinces during the study period

bvFTD = behavior variant of frontotemporal dementia; CBS = corticobasal syndrome; FTD-ALS = frontotemporal dementia–amyotrophic lateral sclerosis; nfvPPA = nonfluent variant of primary progressive aphasia; PSP = progressive supranuclear palsy; uPPA = unspecified primary progressive aphasia.

View this table:
Table 1

Clinical and demographic characteristics of incident cases of FTLD at the time of assessment (Salento-Brescia Registry, 2017)

The mean age at diagnosis was 71.29 (SD 7.82) years, and the median interval between symptom onset and diagnosis was 24.73 (range 3.07–120.55) months. Overall, 51 cases with FTLD (80.95%) were >64 years of age. The youngest age at onset was 48 years; the oldest was 84 years. All patients underwent brain structural imaging (n = 60 MRI scans and n = 3 CT scans), which documented typical FTLD traits in 89% of included individuals in the absence of stroke or significant small vessel ischemic disease. AD diagnosis was further ruled out by CSF analysis (namely tau, phospho-tau, and β-amyloid42 doses) in 32 of the cases (50.8%). In particular, CSF analysis in patients with CBS was available in 2 of 7 cases: 1 patient had unremarkable CSF tau and β-amyloid42 doses, and the other one showed high CSF tau and borderline amyloid levels but presented with a clinical picture characterized since the onset of disease by predominant apraxia and extrapyramidal signs (asymmetric muscular rigidity and bradykinesia, right > left) with relative preservation of memory functions. Furthermore, his brain MRI showed a marked diffuse cortical atrophy particularly in the frontal and temporal lobes (left > right).

Incidence rates for FTLD-associated syndromes in the 2 provinces were 3.05 (range 2.34–3.90) per 100,000 person-years (py), while the age-sex–standardized incidence rate was 3.09 (2.95–3.23) per 100,000 py. This incidence would yield 1,873 estimated incident cases of FTLD in the whole Italian population ignoring mortality. We estimated a lifetime risk for Italian population of 0.25% both for men and women (1:400).

Thirty-one incident cases (49.21%) were male and 32 (50.79%) were female, with a similar incidence rate (p = 0.93). In particular, incidence rates for FTLD-associated syndromes were 3.08 (2.09–4.38) per 100,000 py for men and 3.02 (2.06–4.26) per 100,000 py for women.

The population showed a progressive increase in FTLD incidence across age groups, reaching its peak in the 75- to 79-year-old group, with an incidence rate of 15.97 (8.94–26.33) per 100,000 py in this age group (figure 3 and table 2).

Figure 3
Figure 3 Frontotemporal lobar degeneration incidence by age and sex in the 2 Italian provinces
View this table:
Table 2

Incidence rates, number of cases, and number of person-years by age group and sex (Salento-Brescia Registry, 2017)

Considering the 2 provinces separately, 28 and 35 cases of FTLD-associated syndromes were diagnosed in the Lecce and Brescia areas, respectively.

The age-sex–standardized incidence rate recorded in the province of Lecce was 3.37 (3.22–3.52) per 100,000 py, while the crude incidence rate was 3.49 (2.32–5.04) per 100,000 py. The age-sex–standardized incidence rate in the province of Brescia was 2.92 (2.78–3.05) per 100,000 py, while the crude incidence rate was 2.77 (1.93–3.85) per 100,000 py. No significant difference was found in crude incidence between the 2 provinces (p = 0.362), but a slight higher age-sex–standardized incidence rate was found in the province of Lecce (rate ratio 1.15, p < 0.001).

Age at diagnosis was 69.39 (SD 6.47) years in the province of Lecce and 72.8 (SD 8.54) years in the province of Brescia. Twelve (42.86%) women in the province of Lecce and 20 (57.14%) women in the province of Brescia were diagnosed. No significant differences in age at diagnosis (p = 0.077), sex (p = 0.382), and education (p = 0.854) between the 2 provinces were found. However, we found a significant difference in the onset-diagnosis interval (p = 0.007), which was higher in the province of Lecce (median 35.53 months, range 3.76–105.16 months) compared to the province of Brescia (median 20.69 months, range 3.07–120.55).

Sixteen (57.14%) patients in the province of Lecce and only 1 (2.86%) patient in the province of Brescia showed a second phenotype (p < 0.001) during follow-up assessment in the first year.

Phenotype at diagnosis was significantly different between the 2 provinces, with nfvPPA predominantly diagnosed in the province of Brescia (42.86%) and bvFTD in the province of Lecce (50.00%, p = 0.02).

Discussion

The present population-based study claims that FTLD is more common than previously described, with an incidence of ≈3 per 100,000 py, higher than what has been generally reported for amyotrophic lateral sclerosis and other rare neurodegenerative diseases.19

Even though the present work is characterized by a short observation interval, it has covered one of the largest source populations for incidence estimation, has considered the revised criteria for FTLD, has taken into consideration brain imaging and CSF markers in the diagnostic workup, has included the overall spectrum of FTLD phenotypes, and has been carried out in 2 well-defined geographic areas.

Previous studies assessing FTLD incidence have considered early-onset cases9,20 in relatively small populations.20,21 The only available study with a similar design and a comparable sample size was conducted in the county of Cambridgeshire,22 in which the authors found comparable overall incidence estimates but a different phenotype distribution and some differences in age distribution (figure 4). Indeed, incidence rates in the Italian study appear lower in the younger groups, with no cases <48 years of age and with an incidence rate of 0.61 per 100,000 py in the 50- to 54-year-old group, while others22 found an incidence rate of ≈1.00 and 2.90 per 100,000 in the 45- to 49-year-old and 50- to 54-year-old groups, respectively. The most pronounced difference was found in the 65- to 69-year-old age group, for which we estimated an incidence of 12.10 per 100,000, while UK counties showed an incidence of ≈6.50 per 100,000 py. This low incidence determines the presence of 2 peaks in the UK age-incidence curve in the 60- to 64-year-old and 75- to 79-year-old groups, while we found only 1 peak in the 75- to 79-year-old range. In the latter group, we found an incidence of 15.97 per 100,000 py, comparable to the highest peak (16.1 per 100,000 py) in the United Kingdom in the same age group (figure 4). Furthermore, the Cambridgeshire study showed a large proportion of PSP and CBS (>50%) compared to PPA and bvFTD.

Figure 4
Figure 4 Frontotemporal lobar degeneration incidence in the 2 Italian provinces compared to the 2 UK counties (estimated from figure 3A of reference 21)

Phenotype distribution was different across the 2 regions in our study, with more bvFTD cases in the south and more PPA cases in the north. This difference in phenotype distribution within the study and across studies could be determined by different underlying genotypes across different populations. A difference related to ethnicity has been proposed for C9orf72, with clustering in populations of northern European (Viking) descent.23 The observed distribution of phenotypes in our study does not support this hypothesis; conversely, the largest proportion of bvFTD, often associated with C9orf72, is within the province of Lecce, the southern region. An alternative explanation is that the different distribution could be determined by the presence of distinct and specific expertise in recruiting centers and investigators involved in each registry.

Some degree of ascertainment bias is present in any epidemiologic study,24 but it is particularly relevant when the disease is characterized by extensive clinical heterogeneity like FTLD. One possible limitation of our study is the potential underascertainment due to misdiagnosis and lack of referral by other neurologists, geriatricians, and psychiatrists to the multidisciplinary registry.

We did not diagnose any case of svPPA, probably because of the rarity of the syndrome, as confirmed in the Cambridgeshire registry in which only 1 incident case was found over 2 years.

Estimates in incidence rates are slightly higher than what is found in previous studies that are based on selected young age groups (<65 years) or that included only specific syndromes. We estimated the lifetime risk of ≈1:400, very similar to the overall risk of amyotrophic lateral sclerosis.25 This risk is much higher than what has been calculated in the Cambridgeshire study (1:700), probably because of the unexplained incidence drop in the 65- to 69-year-old group and the higher life expectancy of the Italian population.

A relevant new finding of this study is that >80% of the cases were >64 years of age. This age distribution is quite different from previous works, possibly indicating that extending the sampling to the entire population, as in this study, could highlight a different age distribution with an incidence peak in the mid-70s. Moreover, the source population of the present study, compared to autopsy-based studies, may be different in that the latter have a lower percentage of elderly individuals, generally with fewer women and minorities; important selection bias of autopsy and tertiary centers series has been largely confirmed across neurodegenerative disorders.26,–,28

Using a syndrome approach and looking primarily at the presence of frontal syndromes, previous investigators11 found that 20% of individuals >85 years of age presented with a frontal behavioral syndrome and 3% had a diagnosis of bvFTD according to DSM-III-R criteria for dementia, thus confirming the presence of significant frequency of FTLD even in the oldest groups.

The age range of FTLD onset is very wide, as previously reported21: in this study, the youngest age at onset was 48 years and the oldest was 84 years. Overall, our age-specific incidence rates were slightly lower in young groups compared to previous studies,9,21 while we found comparable or higher incidence rates in the older groups.21,22,29 However, it should be considered that comparisons based on very large age intervals could be influenced by differences in the age structure of the populations.

There are several limitations and strengths of the study. Collecting incident cases is challenging but represents the best estimation of the new burden of a disease per year in a specific population and allows characterization of the phenotype spectrum in a complex disease such as FTLD. In general, the incidence of dementia in Italy is 12.47 per 1,000 py. This is in line with other European countries.30 The awareness of dementia in Italy is high, and the presence of the national health system with free access to health care favors the diagnostic process. Data were based on the first year of data collection, which hinders a possible selection bias toward the enrollment of prevalent rather than apparent incident cases. This could be supported by the wide range of disease duration in our series. On the other hand, registries tend to miss more cases in the first years when the logistic infrastructure is still to be properly established.31 With the complete implementation of all the mechanisms of the multisource registry, both populations become more aware of the registry, improving the specificity of the diagnosis of both referral and peripheral centers of the network.32 Nevertheless, our estimates are among the highest reported in available literature. Moreover, in this epidemiologic study, we included patients with a clinical diagnosis of FTLD according to the revised criteria,4,5,12,13 but we cannot ascertain neuropathologic features. It might be possible that especially the oldest cases have underlying non-FTLD pathologies.

There is a clear decrease in the incidence after 80 years of age, which is similar to that observed in other neurodegenerative diseases such as Parkinson disease33 and amyotrophic lateral sclerosis.19 This could be secondary to the decrease in the number of individuals susceptible to the disease. Alternatively, it could be a bias due to the lack of referral and diagnosis of older patients, who are less likely to be evaluated in specialist clinics and have considerable multimorbidity or atypical presentations of disease.34 The role of decline of competing mortality and associated risk factors in older age groups should not be underestimated.

Diagnostic certainty and accuracy are generally an issue in most population-based studies in which the number of complex procedures is probably limited. In this study, however, all of the diagnoses were confirmed by dementia specialists. The inclusion of FTLD-mimic syndromes is still possible but unlikely, considering that the clinical diagnosis was confirmed by dementia clinical expert, an MRI read by a neuroradiologist who was blinded to the study goals, CSF results, and the complete neuropsychological assessment, which make the diagnosis of FTLD the best possible antemortem in this cohort. The likelihood of inclusion of mimic syndromes increases with age, but it is important to underline that the presence of vascular lesions does not exclude FTLD diagnosis in this older age group.35 Follow-up evaluations will consolidate the validity of the initial diagnosis. The quality of the diagnosis was higher compared to previous studies in a population-based setting based fundamentally on clinical interviews or chart reviews. The diagnosis of neurodegenerative diseases has some limitations even in tertiary centers with overall accuracy of ≈80% when neuropathology is used as the gold standard.

All the phenotypes currently considered in the FTLD spectrum were included in the present study. There is still the possibility that very severe cases, milder cases, or atypical phenotypes were not referred to the registry. However, this is less likely than in clinical series in which several determinants, including younger age, family history, and proximity to the referral center, may be influential.

FTLD is more common than previously described, with a maximum incidence in the mid-70s. Because nearly 4 of 5 patients had an age at onset >65 years, older ages should be considered with more focus on the identification of cases of FTLD both in clinics and in population-based studies. The consistency of the results between the 2 areas with 2 different teams strengthens the generalizability of the results to Italy and probably to Europe. The extensive use of registries in different populations to identify and follow up patients with FTLD should be considered in the near future to have accurate information on FTLD epidemiology, including the distribution of different phenotypes.31 Collaborative work of multinational registries, studying different populations and ethnicities, would be helpful. Increasing the understanding of FTLD and its epidemiology will help to promote appropriate public health service policies and treatment approaches.

Author contributions

G. Logroscino: study concept, design, acquisition of data, writing initial draft study supervision, grant founding for the project. M. Piccininni: statistical analysis and interpretation. G. Binetti, C. Zecca, R. Turrone, R. Capozzo, R. Tortelli, P. Battista, E. Bagoj, R. Barone, S. Fostinelli, L. Benussi, R. Ghidoni, A. Padovani, and S. Cappa: acquisition of data, final revision of the manuscript. A. Alberici and B. Borroni: study design, acquisition of data, writing initial draft.

Study funding

This work was supported by grants from Regione Puglia (DGR No. 1284-27.05.2015) for the project “Registro Regionale per la SLA, la FTD-P e le patologie affini in Regione Puglia” (SLAPDem register, slapdem.it) and from the Italian Ministry of Health (Ricerca Corrente).

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Acknowledgment

The authors are grateful to all the SLAPDem Group: Antonella Vasquez (Casarano), Bonaventura Ardito (Andria), Bruno Brancasi (Bari), Bruno Passarella (Brindisi), Carlo Avolio (Foggia), Cecilia Nozzoli (Brindisi), Ciro Mundi (Foggia), Elena Carapelle (Foggia), Filippo Tamma (Acquaviva delle Fonti), Francesco Lincesso (Taranto), Francesco Valluzzi (Monopoli), Gianluca Masi (Bari), Giorgio Trianni (Lecce), Giovanni Zimatore (Barletta), Giuseppe Rinaldi (Bari), Isabella Laura Simone (Bari), Marcella Caggiula (Lecce), Maurizio Angelo Leone (San Giovanni Rotondo), Michele De Mari (Andria), Michele Zarrelli (San Giovanni Rotondo), Renato Sambati (Nardò), Rocco Scarpello (Casarano), Saverio Internò (Taranto), Vincenzo De Marco (Brindisi), and Bruno Tartaglione (Bari). They also are grateful to the Coordinating Group: Giancarlo Logroscino (principal investigator), Chiara Zecca, Cinzia Musarò, Marco Piccininni, Maria Rosaria Barulli, Petronilla Battista, Roberta Barone, Rosa Capozzo, and Rosanna Tortelli.

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received August 2, 2018.
  • Accepted in final form January 19, 2019.

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