Clinical Syndromes and Epidemiology of the FTLD-Spectrum Disorders in Latin America

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.

“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.

http://hinari-gw.who.int/whalecomwww.tandfonline.com/whalecom0/action/showPopup?citid=citart1&id=F0002&doi=10.1080/13554790802632967

“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






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


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






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






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


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






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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Clinical Syndromes and Epidemiology of the FTLD-Spectrum Disorders in Latin America

Health & Medicine

Transcript of Clinical Syndromes and Epidemiology of the FTLD-Spectrum Disorders in Latin America