The document discusses clinical syndromes and epidemiology of frontotemporal lobar degeneration (FTLD) in Latin America. It outlines that the document will cover clinical syndromes of FTLD, prevalence and incidence of FTLD in LA, estimating number of FTLD cases in LA, mean survival time of FTLD, and economic impact of FTLD in LA. Studies in LA show the prevalence of dementia increases with age and is higher in women than men. Alzheimer's disease is the most common cause of dementia found in LA, followed by vascular dementia.

1. Clinical syndromes and
epidemiology of the FTLD-
spectrum disorders in Latin
America

2. Outline
• Clinical syndromes of FTLD.
• Prevalence and incidence of FTLD.
• Estimating number of cases of the FTLD in LA.
• Mean survival time of FTLD.
• Economic impact of FTLD in LA.

3. Outline
• Clinical syndromes of FTLD.
• Prevalence and incidence of FTLD.
• Estimating number of cases of the FTLD in LA.
• Mean survival time of FTLD.
• Economic impact of FTLD in LA.

4. “On the relationship between senile
cerebral atrophy and aphasia”
.… The patient had marked aphasia: his understanding of
speech was substantially, though not completely, disturbed.
He could understand simple questions about generalities and
about things familiar to him; other things he did not understand
at all. The patient was over-talkative. If his sentences were
about simple things they were occasionally correct, otherwise
they were unintelligible. This was partly because correct words
were used in the wrong order and partly because some of his
words were nonsensical. This occasionally resulted from the
re-arrangement of consonants; so, for example, for the target
word ‘locomotive’, he produced ‘colmolotive’; for the word
‘Kleiderkasten’, he said ‘Reideklasten’; and so on…In reading
aloud, for Ostende he responded ‘Oste, ost, u te te, Ostus,
tentinde…….
PICK A. Über die Beziehungen der senilen Atrophie zur Aphasie.
Prager Medizinische Wochenschrift,17: 165-167, 1892.

5. Arnold Pick and “focal dementia”
“….the clinical findings of senile dementia can be interpreted as a mosaic of
circumscribed deficits of higher mental abilities (‘Herderscheinungen’); this fact
may fail to be revealed when the process of atrophy occurs simultaneously at
many places, thereby masking the appearance of the single symptoms”
PICK A. Senile Hirnatrophie als Grundlage für Herderscheinungen.
Wiener Klinische Wochenschrift, 14:403-404, 1901.

6. Alzheimer and histopathological description
ALZHEIMER A. Über eigenartige Krankheitsfälle
des späteren Alters. Zeitschrift für die gesamte
Neurologie und Psychiatrie, 4: 356-385, 1911.

7. “Pick’s disease” or “Pick complex”?
Pick’s disease
• Europe: Clinical diagnosis, with or without pathologically proven Pick bodies.
• America: Pathological diagnosis, irrespective of the clinical presentation.
Pick complex
CBD PSP PPA bvFTD FTLD-ALS

8. Fronto-temporal lobar degeneration
• Clinical, genetic, and pathological heterogeneous group of disorders.
• Is a macro-anatomical descriptive term reflecting the relatively selective
involvement of frontal and temporal lobes.
• The clinical spectrum:
– Predominant behavioral symptoms: behavioral variant FTLD (bvFTD).
– Deterioration of language function: Primary Progressive Aphasia (PPA)
• Progressive Nonfluent Aphasia (PNFA).
• Semantic Dementia (SD).
• Logopenic Progressive Aphasia (logopenic PPA).

9. International consensus criteria for behavioural
variant FTD
A. Early behavioural disinhibition.
B. Early apathy or inertia.
C. Early loss of sympathy or empathy.
D. Early perseverative, stereotyped or compulsive/ritualistic behaviour.
E. Hyperorality and dietary changes.
F. Neuropsychological profile: executive/generation deficits with relative sparing of memory and
visuospatial functions.
Rascovsky K, et al. Brain 2011;134:2456-2477.

10. Primary Progressive Aphasia
Progressive aphasia nonfluent Semantic dementia Logopenic aphasia
At least one of the following: Both of the following: Both of the following:
 Agrammatism.  Impaired confrontation naming  Impaired single-word retrieval in
 Effortful, halting speech with inconsistent  Impaired single-word comprehension spontaneous speech and naming.
speechsound errors and distortions At least 3 of the following:  Impaired repetition of sentences and
phrases.
At least 2 of 3 of the following:  Impaired object knowledge,
particularly for low frequency or
At least 3 of the following:
 Impaired comprehension of syntactically
complex sentences. low-familiarity items  Speech (phonologic) errors in
spontaneous speech and naming.
 Spared single-word comprehension.  Surface dyslexia or dysgraphia
 Spared single-word comprehension
 Spared object knowledge  Spared repetition. and object Knowledge.
 Spared speech production (grammar  Spared motor speech.
and motor speech)  Absence of frank agrammatism.

11. Outline
• Clinical syndromes of FTLD.
• Prevalence and incidence of FTLD.
• Estimating number of cases of the FTLD in LA.
• Mean survival time of FTLD.
• Economic impact of FTLD in LA.

12. Estimated growth of dementia
The number of people with dementia will roughly double every 20 years,
with the biggest increases in developing countries
Alisson Abbott. Nature 2011;475:S2-S4

13. Prevalence of different types of dementia by
age group
Prevalence of dementia in Canada, by type of Prevalence of different types of dementia
dementia, sex and age group- rates per 1,000 in the 45- to 64-year age group per 100,000
population in Cambridgeshire
Women Men Both Prevalence
rate/1,000 rate/1,000 rate/1,000 Diagnosis
(95% CI)
All dementia 86 69 80
65-74 28 19 24 Alzheimer’s disease 15.1
75-84 116 104 111
Frontotemporal dementia 15.1
85+ 371 287 345
Alzheimer’s disease 58 38 51
Vascular dementia 6
65-74 14 5 10
75-84 78 55 69
Huntington’s disease 14
85+ 288 196 260
Vascular dementia 12 19 15
65-74 4 8 6 Parkinsonian syndromes 5
75-84 19 31 24
85+ 46 52 48
CSHA Working group. Neurology 2000;55:66-73 Ratnavalli E, et al. Neurology 2002;85:1615

14. Studies of prevalence of FTLD
Point estimate per
Location Cases (n) Case definition 95 % CI
100,000 in 45–64 y/o
Zuid-Holland, Netherlands
55 bvFT only 4.0 2.8 – 5.7
(Rosso et al. 2003)
Cambridgeshire, UK
11 bvFTD + PPA 15 8.4 – 27.0
(Ratnavalli et al. 2002)
London, UK
18 bvFTD 15.4 9.1 – 24.3
(Harvey et al. 2003)
Brescia, Italy
213 bvFTD + PPA 22 17 – 27
(Borroni et al. 2010)
Ibaraki, Japon
17 bvFTD only 2.0 1.3 – 3.2
(Ikejima et al. 2009)
Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335

15. Studies of incidence of FTLD
Location Cases (n) Case definition Rate per 100,000 per year 95 % CI
Rochester, Minnesota
4 bvFTD + PPA 4.1 (rango edad: 40-69) 2.8 – 5.7
(Knopman et al. 2004)
Cambridgeshire, UK
16 bvFTD + PPA 3.5 (rango edad: 45-64) 8.4 – 27.0
(Mercy et al. 2008)
Girona, Spain
14 bvFTD + SD 2.7 (rango edad: 45-64) 1.3 – 3.2
(Garre-Olmo et al. 2010)
Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335

16. Frequency of FTLD in Brescia county according
to age at onset of symptoms (n=226)
22/100,000 78/100,000 54/100,000
n=108 n=97 n=21
Borroni B, et al. J Alzheimers Dis 2010;19:111-116

17. The very high estimates of prevalence in persons over
age 65 years don’t reflect neuropathological FTLD
Total Functional disability 1998 criteria Common
sample and neuroimaging sample sample
(n=176) sample (n=154) (n=152) (n=137)
Gender (F/M) 72/104 65/89 64/88 60/77
Age at onset 58.1 (10.9) 58.4 (11.1) 57.8 (10.9) 58.1 (11.1)
Age at initial evaluation 61.5 (10.9) 61.7 (11.0) 61.3 (10.9) 61.5 (11.0)
Age at death 66.1 (11.6) 66.4 (11.7) 65.8 (11.6) 65.8 (11.6)
Education 14.2 (3.5) 14.3 (3.4) 14.2 (3.5) 14.2 (3.5)
MMSE 22.2 (7.0) 22.5 (6.9) 22.2 (7.1) 22.3 (7.1)
Duration: onset-initial evaluation 3.2 (2.7) 3.2 (2.6) 3.2 (2.6) 3.3 (2.6)
Duration: onset-death 7.8 (3.9) 7.6 (3.9) 7.7 (3.9) 7.6 (3.9)
Duration: initial evaluation-death 4.6 (3.9) 4.4 (3.1) 4.5 (3.3) 4.3 (3.1)
Rascovsky K, et al. Brain 2011;134:2456-2477.

18. Outline
• Clinical syndromes of FTLD.
• Prevalence and incidence of FTLD.
• Estimating number of cases of the FTLD in LA.
• Mean survival time of FTLD.
• Economic impact of FTLD in LA.

19. Prevalence of dementia in eight Latin American
studies, according to age groups
Nitrini R, et al. International Psychogeriatrics 2009;21:622-630.

20. Prevalence of dementia according to gender between
pooled data of Latin American and European studies
Latino american studies European studies
Women Men Women Men
Age Dem Partic. Prevalence Dem Partic. Prevalence Preval. Preval. (%)
n n (%) (95% CI) n n (%) (95% CI) (%)
65-69 149 5620 2.65 (2.25-3.10) 79 3 479 2.27 (1.80-2.81) 1.0 1.6
70-74 196 4781 4.10 (3.55-4.69) 65 2 317 2.81 (2.17-3.57) 3.1 2.9
75-79 293 3802 7.71 (6.89-8.59) 112 1 888 5.93 (4.90-7.09) 6.0 5.6
80-84* 291 2326 12.51 (11.17-13.94) 162 1 489 10.88 (9.34-2.55) 12.6 11.0
85-89 281 1244 22.59 (20.30-24.97) 182 960 18.96 (16.49-21.55) 20.2 12.8
90+ 189 500 37.80 (33.56-42.28) 105 390 26.92 (22.54-31.67) 30.8 22.1

21. Causes of dementia in the 103 cases: Lima-Peru
Diagnosis n %
Probable AD 51 49.5
Possible AD 7 6.8
Vascular dementia 9 8.7
AD with CVD 16 15.5
Parkinson’s dementia 3 2.9
Lewy-body dementia 2 1.9
Frontotemporal dementia 2 1.9
Undetermined cause 13 12.7
Custodio N, et al . An Fac Med 2008;69(4):233-238

22. Causes of dementia in individuals over 65 years
of age: Population-based three studies in LA
Lima Catanduva Sao Paulo
Diagnosis (Total sample: 1532) (Total sample: 1656) (Total sample: 1563)
n % n % n %
AD 58 56.3 65 55.1 64 59.8
VD 9 8.7 11 9.3 17 15.9
AD+VD 16 15.5 17 14.4 9 8.4
PD 3 2.9 4 3.4 1 0.9
FTD 2 1.9 3 2.6 - -
LBD 2 1.9 2 1.7 1 0.9
Vitamin B12 deficiency - - 1 0.8 - -
Alcoholic dementia - - - - 5 4.7
Undetermined cause 13 12.7 15 12.7 10 9.3
Total 103 100.0 118 100.0 107 100.0

23. Prevalence of presenile dementia
in a tertiary outpatient clinic: Sao Paulo-Brazil
Etiology n %
Vascular dementia 52 36.9
Probable AD 18 12.8
Possible AD 12 8.5
Traumatic brain injury 13 9.2
Frontotemporal dementia 7 5.0
Alcoholic dementia 7 5.0
Normal pressure hydrocephalus 6 4.2
Depression 6 4.2
Anoxic encephalopaty 4 2.8
Miscellanea 16 11.3
Fujihara S, et al. Arq Neuropsquiatr 2004;62:592-595.

24. Estimating number of cases of the FTLD in Peru
Point Estimating
Censo No of
estimate number of
2007 cases
per 100,000 cases
Over 65 y/o 1’764,687 2 6 105
15 622
45-64 y/o 4’147,131 -
22 912
Number of cases of FTLD in Peru: 727 - 1017

25. Outline
• Clinical syndromes of FTLD.
• Prevalence and incidence of FTLD.
• Estimating number of cases of the FTLD in LA.
• Mean survival time of FTLD.
• Economic impact of FTLD in LA.

26. Studies of survival in FTLD
Basis of No of Mean aged Delay in Survival from
Location
diagnosis subjects at diagnosis diagnosis onset or diagnosis
Survival from diagnosis
Clinical
San Francisco (Robertson et al. 2005) 177 58.5 ± 9.4 4.5 ± 2.9 3.6 ± 0.4
diagnoses
Pathologically
San Diego (Rascovsky et al. 2005) 70 65 ± 9.4 4.0 ± 2.8 4.2
confirmed
Clinical
Sidney (Garcin et al. 2009) 91 57.2 ± 8.2 3.6 ± 2.5 4.2 ± 0.8
diagnoses
Pathologically
Cambridge and Sidney (Hodges et al. 2003) 61 61.5 ± 7.6 3 3.0 ± 0.4
confirmed
Survival from onset
Pathologically
Rochester MN (Josephs et al 2005) 45 57.3 ± 11.1 - 6.6
confirmed
Pathologically
Philadelphia (Xie et al. 2008) 71 61.0 ± 9.5 1 ±1 6.6 ± 0.5
confirmed
Clinical
Netherlands (Chiu et al. 2010) 354 57.5 ± 8.9 - 9.9 ± 0.7
diagnoses
Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335

27. FTD follows a more malignant disease
course than AD once dementia is clinically recognized
Rascovsky K, et al. Neurology 2005;65:397-403

28. Behavioral variant DFT (bvDFT) progresses more
rapidly than other subtypes
Roberson ED, et al. Neurology 2005;65:719-725

29. Survival in semantic dementia overlaps
Alzheimer’s disease
Roberson ED, et al. Neurology 2005;65:719-725

30. Patients with definite bvDFT have a poor prognosis
which is worse if language deficits are also present
Garcin B, et al. Neurology 2009;73:1656-1661

31. Outline
• Clinical syndromes of FTLD.
• Prevalence and incidence of FTLD.
• Estimating number of cases of the FTLD in LA.
• Mean survival time of FTLD.
• Economic impact of FTLD in LA.

32. Evaluation of costs of Alzheimer-type dementia
in Bs As according to patient’s place of residence
Allegri RF, et al. International Psycogeriatrics 2007;19:705-718

33. Evaluation of costs of Alzheimer-type dementia
in Bs As by severity of dementia
Allegri RF, et al. International Psycogeriatrics 2007;19:705-718

34. Direct costs of Alzheimer’s, frontotemporal and
vascular dementia in Argentina: 2002-2008
Rojas G, et al. International Psycogeriatrics 2011;23:554-561

35. Drug-medicines cost analysis of Alzheimer’s, fronto-
temporal and vascular dementia in Argentina
Rojas G, et al. International Psycogeriatrics 2011;23:554-561

36. Conclusions
• Historically, researchers have used a varied nomenclature to describe FTLD.
• Clinical profile and the underlying pathological changes are heterogeneous in FLTD.
• Two broad presentations are recognized: progressive deterioration in social function and
personality and insidious decline in language skills.
• Several research groups have used passive surveillance methods to estimate prevalence or
incidence of the cognitive syndromes of the FTLDs.
• Epidemiological studies suggest that FTLD is the second most common cause of young onset
dementia after AD.
• bvDFT progresses more rapidly than other subtypes, which is worse if language deficits are
also present.
• In Latin America, the costs to treat DFT are higher than for AD, but less than for DV, and has
high costs in the use of psychotropic drugs.

37. Nilton Custodio
niltoncustodio@neuroconsultas.com
www.neuroconsultas.com
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