Compound heterozygosity of 2 novel MAPT mutations in frontotemporal dementia.

Intronic MAPT mutations altering exon 10 splicing lead mainly to an increase of 4Rtau. The objective of this study is to report clinical, genetic, and neuropathological data of an apparently sporadic early onset frontotemporal dementia (FTD) case associated with 2 novel intronic MAPT gene mutations IVS10+4A > C and IVS9-15T > C that increase 3Rtau. Methods and subjects used are clinical, neuroradiological, and neuropathological examination; molecular genetics of MAPT, PGRN, and other relevant genes. Exon 10 splicing tested with minigene constructs. Tau deposits detected by immunohistochemistry. Sarkosyl-insoluble and soluble tau investigated by immunoblotting. Two novel MAPT mutations IVS10+4A > C and the IVS9-15T > C transmitted by the unaffected parents were identified. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analyses on minigenes and in brain tissue showed that both mutations cause an increase of tau mRNA (messenger ribonucleic acid) transcripts lacking exon 10 only in the patient. Immunohistochemistry and immunoblotting of the patient's brain revealed tau deposits composed mostly of 3Rtau isoforms with a predominance of the shorter 3Rtau isoforms. The compound heterozygosity of the patient increasing 3Rtau seems to be responsible for the disease and furthermore suggests that sporadic cases can be caused by genetic mutations.

Fronto-temporal dementia presenting as Geschwind's syndrome.

Geschwind described a syndrome (Geschwind syndrome, GS) in patients with temporal lobe epilepsy, characterized by sexual behavioural disorders, hyper-religiosity, hypergraphia and viscosity. In this report we describe a patient affected by fronto-temporal dementia (FTD), who showed all the personality changes of GS without having epilepsy, and suggest that clinicians should be aware of several other features in FTD, such as hyposexuality and hypergraphia, which are usually not noted during the diagnostic evaluation.

Role of functional performance in diagnosis of dementia in elderly people with low educational level living in Southern Italy.

BACKGROUND AND AIMS: Diagnosis of dementia is often difficult in subjects with low educational level. Our aim was to evaluate the role of functional performance and the possibility of preferring scores of activities of daily living (ADL) and instrumental activities of daily living (IADL) in screening elderly people for diagnosis of dementia in a rural population of Southern Italy with a very high percentage of non-educated subjects. METHODS: a random sample of 300 residents, out of 1089 subjects over 60 years of age living in San Marcellino (Caserta, Campania), received door-to-door visit for information about their medical history, with clinical evaluation of general geriatric conditions, including the cumulative illness rating scale (CIRS). Dementia was diagnosed if subjects had a Clinical Dementia Rating score (CDR) > or = 1 and according to the criteria of DSMIV, but not according to scores on the Mini Mental State Examination (MMSE), ADL and IADL. Two hundred and nineteen normal subjects (NS) and 75 patients with dementia (DP) were evaluated. RESULTS: in NS, their mean age- and education-corrected MMSE score was 22.15 (lower than the normal cut-off value of 23.8) and 12.60 in DP (p<0.0001). In NS, the mean ADL score was higher than in DP (5.53 vs 2.64, p<0.0001); only age was correlated with ADL scores (coeff=-0.44, t=-4.557, p<0.0001). Assuming age as covariate, ADL scores highly differentiated DP from NS (F(1, 289)=26.083, p<0.0001). In both sexes, mean IADL scores were higher in NS than in DP (4.46 vs 1.80 in men, p<0.0001; 6.85 vs 2.31 in women, p<0.0001). Age and education did not influence IADL scores in men, but age greatly affected performance in women. IADL scores clearly differentiated NS from DP. In NS, a positive correlation was evident between ADL and IADL scores (r=0.234, p<0.0005), but neither scores correlated with the MMSE scores, even when correlation was performed separately for men and women. In DP, a strong correlation was observed between ADL and IADL scores (r=0.709, p<0.0001) and significant correlations were also evident between the scores of MMSE and both ADL (r=0.492,p<0.0001) and IADL (r=0.398, p<0.0004). CONCLUSIONS: in a rural community with a high prevalence of non-educated subjects, cognitive impairment is related to education, whereas independent functioning is limited mainly to age and not to cognition, if the latter remains (relatively) unimpaired. These results point to the importance of an "ecological" approach to the evaluation of elderly people, particularly those living in small rural communities, where education and the social environment may give rise to difficulties in diagnosis of dementia. The assessment of functional autonomy by ADL and IADL scales may be a better screening tool in diagnosing dementia than the MMSE scores.