clinical syndromes and epidemiology of the ftld-spectrum disorders in latin america
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Belohorizonte 06 de Junio 2012TRANSCRIPT
Clinical syndromes and epidemiology of the FTLD-spectrum disorders in Latin
America
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.
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.
“On the relationship between senile cerebral atrophy and aphasia”
PICK A. Über die Beziehungen der senilen Atrophie zur Aphasie. Prager Medizinische Wochenschrift,Prager Medizinische Wochenschrift,17: 165-167, 1892.17: 165-167, 1892.
.… 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…….
Arnold Pick and “focal dementia”
PICK A. Senile Hirnatrophie als Grundlage für Herderscheinungen. Wiener Klinische Wochenschrift, 14:Wiener Klinische Wochenschrift, 14:403-404, 1901.403-404, 1901.
“….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”
Alzheimer and histopathological description
ALZHEIMER A. Über eigenartige Krankheitsfälle des späteren Alters. Zeitschrift für die gesamteZeitschrift für die gesamteNeurologie und Psychiatrie, 4: 356-385, 1911.Neurologie und Psychiatrie, 4: 356-385, 1911.
“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
bvFTDPPAPSPCBD FTLD-ALS
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).
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.Rascovsky K, et al. Brain 2011;134:2456-2477.
Primary Progressive Aphasia
Progressive aphasia nonfluentAt least one of the following: Agrammatism. Effortful, halting speech with inconsistent
speechsound errors and distortions
At least 2 of 3 of the following: Impaired comprehension of syntactically
complex sentences. Spared single-word comprehension. Spared object knowledge
Semantic dementiaBoth of the following: Impaired confrontation naming Impaired single-word comprehension
At least 3 of the following: Impaired object knowledge,
particularly for low frequency or low-familiarity items
Surface dyslexia or dysgraphia Spared repetition. Spared speech production (grammar
and motor speech)
Logopenic aphasiaBoth of the following: Impaired single-word retrieval in
spontaneous speech and naming. Impaired repetition of sentences and
phrases.At least 3 of the following: Speech (phonologic) errors in
spontaneous speech and naming. Spared single-word comprehension
and object Knowledge. Spared motor speech. Absence of frank agrammatism.
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.
Estimated growth of dementia
Alisson Abbott. Nature 2011;475:S2-S4Alisson Abbott. Nature 2011;475:S2-S4
The number of people with dementia will roughly double every 20 years, with the biggest increases in developing countries
Prevalence of different types of dementia by age group
Women rate/1,000
Men rate/1,000
Both rate/1,000
All dementia 86 69 80
65-74 28 19 24
75-84 116 104 111
85+ 371 287 345
Alzheimer’s disease 58 38 51
65-74 14 5 10
75-84 78 55 69
85+ 288 196 260
Vascular dementia 12 19 15
65-74 4 8 6
75-84 19 31 24
85+ 46 52 48
Diagnosis Prevalence (95% CI)
Alzheimer’s disease 15.1
Frontotemporal dementia 15.1
Vascular dementia 6
Huntington’s disease 14
Parkinsonian syndromes 5
Ratnavalli E, et al. Neurology 2002;85:1615Ratnavalli E, et al. Neurology 2002;85:1615
Prevalence of different types of dementia in the 45- to 64-year age group per 100,000 in
Cambridgeshire
Prevalence of dementia in Canada, by type of dementia, sex and age group- rates per 1,000
population
CSHA Working group. Neurology 2000;55:66-73CSHA Working group. Neurology 2000;55:66-73
Studies of prevalence of FTLD
Location Cases (n) Case definition Point estimate per 100,000 in 45–64 y/o 95 % CI
Zuid-Holland, Netherlands
(Rosso et al. 2003)55 bvFT only 4.0 2.8 – 5.7
Cambridgeshire, UK
(Ratnavalli et al. 2002)11 bvFTD + PPA 15 8.4 – 27.0
London, UK
(Harvey et al. 2003)18 bvFTD 15.4 9.1 – 24.3
Brescia, Italy
(Borroni et al. 2010)213 bvFTD + PPA 22 17 – 27
Ibaraki, Japon
(Ikejima et al. 2009)17 bvFTD only 2.0 1.3 – 3.2
Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335
Studies of incidence of FTLD
Location Cases (n) Case definition Rate per 100,000 per year 95 % CI
Rochester, Minnesota
(Knopman et al. 2004)4 bvFTD + PPA 4.1 (rango edad: 40-69) 2.8 – 5.7
Cambridgeshire, UK
(Mercy et al. 2008)16 bvFTD + PPA 3.5 (rango edad: 45-64) 8.4 – 27.0
Girona, Spain
(Garre-Olmo et al. 2010)14 bvFTD + SD 2.7 (rango edad: 45-64) 1.3 – 3.2
Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335
Frequency of FTLD in Brescia county according to age at onset of symptoms (n=226)
Borroni B, et al. J Alzheimers Dis 2010;19:111-116Borroni B, et al. J Alzheimers Dis 2010;19:111-116
n=108 n=97 n=21
22/100,000 78/100,000 54/100,000
The very high estimates of prevalence in persons over age 65 years don’t reflect neuropathological FTLD
Total sample (n=176)
Functional disability and neuroimaging
sample (n=154)
1998 criteria sample (n=152)
Common sample (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.Rascovsky K, et al. Brain 2011;134:2456-2477.
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.
Prevalence of dementia in eight Latin American studies, according to age groups
Nitrini R, et al. International Psychogeriatrics 2009;21:622-630.Nitrini R, et al. International Psychogeriatrics 2009;21:622-630.
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
n
Partic.
n
Prevalence
(%) (95% CI)
Dem
n
Partic.
n
Prevalence
(%) (95% CI)
Preval.
(%)
Preval. (%)
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
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):233-238Custodio N, et al . An Fac Med 2008;69(4):233-238
Causes of dementia in the 103 cases: Lima-Peru
Causes of dementia in individuals over 65 years of age: Population-based three studies in LA
Diagnosis
Lima (Total sample: 1532)
Catanduva (Total sample: 1656)
Sao Paulo (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
Prevalence of presenile dementiain 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.Fujihara S, et al. Arq Neuropsquiatr 2004;62:592-595.
Estimating number of cases of the FTLD in Peru
Censo 2007
No of cases
Point estimate
per 100,000
Estimating number of
cases
Over 65 y/o 1’764,687 2 6 105
45-64 y/o 4’147,131 -15
22
622
912
Number of cases of FTLD in Peru: 727 - 1017
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.
Studies of survival in FTLD
Location Basis of diagnosis
No of subjects
Mean aged at diagnosis
Delay in diagnosis
Survival from onset or diagnosis
Survival from diagnosis
San Francisco (Robertson et al. 2005) Clinical diagnoses 177 58.5 ± 9.4 4.5 ± 2.9 3.6 ± 0.4
San Diego (Rascovsky et al. 2005) Pathologically confirmed 70 65 ± 9.4 4.0 ± 2.8 4.2
Sidney (Garcin et al. 2009) Clinical diagnoses 91 57.2 ± 8.2 3.6 ± 2.5 4.2 ± 0.8
Cambridge and Sidney (Hodges et al. 2003) Pathologically confirmed 61 61.5 ± 7.6 3 3.0 ± 0.4
Survival from onset
Rochester MN (Josephs et al 2005) Pathologically confirmed 45 57.3 ± 11.1 - 6.6
Philadelphia (Xie et al. 2008) Pathologically confirmed 71 61.0 ± 9.5 1 ± 1 6.6 ± 0.5
Netherlands (Chiu et al. 2010) Clinical diagnoses 354 57.5 ± 8.9 - 9.9 ± 0.7
Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335Knopman D, Roberts R. J Mol Neurosc 2011;45:330-335
FTD follows a more malignant diseasecourse than AD once dementia is clinically recognized
Rascovsky K, et al. Neurology 2005;65:397-403Rascovsky K, et al. Neurology 2005;65:397-403
Behavioral variant DFT (bvDFT) progresses more rapidly than other subtypes
Roberson ED, et al. Neurology 2005;65:719-725Roberson ED, et al. Neurology 2005;65:719-725
Survival in semantic dementia overlaps Alzheimer’s disease
Roberson ED, et al. Neurology 2005;65:719-725Roberson ED, et al. Neurology 2005;65:719-725
Patients with definite bvDFT have a poor prognosis which is worse if language deficits are also present
Garcin B, et al. Neurology 2009;73:1656-1661Garcin B, et al. Neurology 2009;73:1656-1661
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.
Allegri RF, et al. International Psycogeriatrics 2007;19:705-718Allegri RF, et al. International Psycogeriatrics 2007;19:705-718
Evaluation of costs of Alzheimer-type dementia in Bs As according to patient’s place of residence
Allegri RF, et al. International Psycogeriatrics 2007;19:705-718Allegri RF, et al. International Psycogeriatrics 2007;19:705-718
Evaluation of costs of Alzheimer-type dementia in Bs As by severity of dementia
Direct costs of Alzheimer’s, frontotemporal and vascular dementia in Argentina: 2002-2008
Rojas G, et al. International Psycogeriatrics 2011;23:554-561Rojas G, et al. International Psycogeriatrics 2011;23:554-561
Rojas G, et al. International Psycogeriatrics 2011;23:554-561Rojas G, et al. International Psycogeriatrics 2011;23:554-561
Drug-medicines cost analysis of Alzheimer’s, fronto-temporal and vascular dementia in Argentina
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.
Nilton [email protected]
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