Sandro Sorbi DIPARTIMENTO DI SCIENZE NEUROLOGICHE E PSICHIATRICHE

Sandro Sorbi DIPARTIMENTO DI SCIENZE NEUROLOGICHE E PSICHIATRICHE

L Ignoto, il Mistero, stimolano il pensiero, sono indispensabili al poeta ed all artista, aprono alla creatività. L Ignoto, il Mistero, sono un dono per gli umili, i semplici, i più, che li sentono come un emanazione divina e perciò non si fanno tante domande, come me in questa notte stellata, ma pregano e si mettono nelle mani di Dio. R. La Capria, Esercizi Superficiali. Nuotando in superficie. Mondadori, 2012. 2

L itinerario diagnostico L imaging, la biochimica liquorale, la genetica, l assessment, la storia. La diagnosi per prevenire? Per curare? Per dissipare dubbi e paure? Per emarginare? 4

DEMENZE PRESENILI Dementia prevalence rates for men and women in 9 different age groups Range di età 30-59 : 250 / 100.000 Range di età 60-64 : 1600 / 100.000

All Causes of Degenerative Dementia Alzheimer s Disease 50-75% Vascular Dementia 25-50% Other Dementias 25% Of all causes Prevalence Rate 31,25 x 10.000 Alzheimer Europe, Rare Forms of Dementia EC Project, 2005

«Other» Degenerative Dementias FAMILIAL ALZHEIMER DISEASE (FAD) FRONTO-TEMPORAL DEGENERATION (FTD) Fronto-temporal dementia (FTD) Primary Progressive Aphasia (PPA) Semantic Dementia (SD) FTD with parkinsonism linked to chromosome 17 (FTDP-17) Pick s disease (PiD) Dementia lacking distinctive histology (DLDH) LEWY BODY DISEASES DEMENTIA WITH LEWY BODIES (DLB) DEMENTIA IN PARKINSON S DISEASE (PDD) Both of these categories though cannot be considered as one single disease, but rather as a spectrum of different diseases, which would individually fall under the definition of rare diseases. CORTICOBASAL DEGENERATION (CBD) PROGRESSIVE SUPRANUCLEAR PALSY (PSP) ARGYROPHILIC GRAIN DISEASE (AGD) FAMILIAL BRITISH DEMENTIA FAMILIAL DANISH DEMENTIA POSTERIOR CORTICAL ATROPHY (BALINT) PRION DISEASES

Sorbi et al. EFNS guidelines for Dementia, 2012, in press

Need to test early intervention: The rapid growth of knowledge about the potential pathogenic mechanisms of AD. There is accruing evidence that, years before the onset of clinical symptoms, there is an AD process evolving along a predictable pattern of progression in the brain.. The neurobiological advantage of earlier intervention within this cascade is clear. Earlier intervention with disease-modifying therapies is likely to be more effective

Marker = Test diagnostico???

MEMORIA EPISODICA IPPOCAMPALE

PIB AMYLOID MCI OKELLO ET AL. NEUROLOGY, 2009 Seventeen of 31 (55%) subjects with MCI had increased 11C-PIB retention at baseline and 14 of these 17 (82%) clinically converted to AD during follow-up.

2332 non-selected brains from 1- to 100-year-old individuals. Of the total cases, 1,031 (44.2%) had β-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy. Tauopathy associated with sporadic Alzheimer disease anticipates amyloid deposition and may begin earlier than previously thought.

TAU PRECOCE E SPECIFICO BETA ASPECIFICO

NEUROIMAGE, 2012

Neurol Sci, 2011 The presence of episodic memory impairment is required for the diagnosis of Alzheimer s dementia by all current criteria. There must be objective evidence of significantly impaired episodic memory on testing, generally consisting of a recall deficit that does not improve significantly with cueing or recognition testing nor after effective encoding of information has been controlled. This neuropsychological feature has been recently proposed as the core criterion for the diagnosis of prodromal AD [4].

Neurological Sciences 2011

Test diagnostici?? Affidabilità? Validità?? Falsi positivi? Falsi negativi?

Neurological Sciances, 2012 After having critically revised the scientific evidence related to the new lexicon and to the new proposed diagnostic criteria, the panel concluded that the proposed new diagnostic criteria and the new proposed lexicon for AD are conceptually attractive. However, the evidence about the instrumental and laboratory markers for the diagnosis of the preclinical and asymptomatic states of the disease are, until to now, insufficient to support the routine clinical use of these investigations.

The Lancet Neurology, 2010 Giorgio Giaccone et al. on behalf of the BrainNet Europe consortium The proposed approach is fraught with three major problems: First, the concept of disease is inextricably associated with signs of malfunction and suffering (as per WHO s definition of disease). Second, there are uncertainties in clinical diagnosis.. Third, this lexicon does not take heed of the mixed pathological changes that underlie dementia and that seem to be more the rule than the exception In conclusion, we do not think that the knowledge available today is sufficient to define AD as proposed by Dubois and colleagues,