Clinical Features And Early Diagnosis Of Behavioral Variant Of Frontotemporal Dementia

Objective To explore the clinical, neuroimaging and genetic features of behavioral variant of frontotemporal dementia( bv FTD) and to investigate the value of Brief Cognitive Impairment Rating Scale(Cog-12) in patients with bv FTD.Methods Seventy-five patients with bv FTD and 22 patients with Alzheimer’ s disease(AD) were retrospectively evaluated by clinical and neuroimaging features from January 2007 to November 2014. The patients with bv FTD were divided into possible bv FTD group( bv FTD-MCI, CDR= 0.5, n= 37) and probable bv FTD group( bv FTD-DEM, CDR=1 to 3, n=38) according to diagnosis criteria of International Behavioural Variant FTD Criteria Consortium and the scores of clinical dementia rating(CDR). Fifty community elderly people were recruited as normal control group. The Addenbrooke’s Cognitive Examination-revised(ACE-R), and Frontal Assessment Battery(FAB)were applied for evaluating cognitive performances in each group. And Cog-12 scale and Frontal Behavioural Inventory(FBI) was applied for caregivers of each group. Genomic DNA was extracted from peripheral blood samples from patients in bv FTD-DEM group, and both of the microtubule associated protein tau( MAPT) and progranulin( PGRN) genes chromosome 9 open reading frame 72(C9orf72) were amplified with PCR and performed to DNA sequencing.Results(1) The prominent symptom of bv FTD-MCI was apathy, while the prominent symptoms of bv FTD-DEM were memory decline, loss of sympathy, speech disorders and nonspecific psychiatric symptoms. The misdiagnosis rate is high(31/38).(2) There were significant differences in the scores of ACE-R, FBI, MMSE, Cog12-1, Cog12-2 between bv FTD-DEM group and AD group( P<0.05). There was significant difference in the score of memory between the two groups( P<0.001). Compared with FAB, ACE-R, the scales of Cog12-1, Cog12-2 and FBI were more able to differentiate bv FTD-DEM from AD.(AUCFBI =0.946,AUCFAB =0.550,AUCACE-R=0.885, AUCCog12-1 =0.920,AUCCog12-2=0.867,all P <0.05);(3) Compared with FAB, ACE-R, the scales of Cog-12, Cog12-1, Cog12-2 and FBI were more able to differentiate bv FTD-MCI from normal controls.( AUCCog12 =0.875,AUCCog12-1 =0.800, AUCCog12-2=0.846, AUCFBI =0.889, AUCFAB =0.808, AUCACE-R=0.708, all P<0.01);(4) MRI studies of bv FTD patients revealed atrophy of the frontal and/or temporal lobes. The pattern of atrophy varies significantly. The atrophy of hippocampus was showed in 8 cases of bv FTD patients;(5) Two novel mutations of MAPT were identified, including 1 missense mutation(p.P313A) in a familial case and 1 missense mutation(p.D177V) in a sporadic case. Compared with non-carriers, the 2 cases were characterized by earlier onset age, more complex symptoms and faster cognitive function decline.Conclusion The early symptoms of bv FTD patients are complex, and easily misdiagnosed. MRI studies show that bv FTD presents with a combination of anterior frontal and temporal cortical atrophy. In comparison with FAB and ACE-R, Cog-12 and FBI differentiate bv FTD better. The combination of behavioral and cognitive scales and genetic tests promotes early diagnosis.