Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementia.

To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) (N=186), frontotemporal dementia (FTD) (N=29), mixed dementia (MXD) (N=28), dementia with Lewy bodies (DLB) (N=11) and Parkinson's disease dementia (PDD) (N=7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)). In FTD patients, we identified dose dependent effects of APOE epsilon4 on the Behave-AD total and cluster aggressiveness scores. APOE epsilon2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found. In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB).

Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program.

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian study.

OBJECTIVE: Given the rather limited knowledge on profiles of neuropsychiatric symptoms (behavioural and psychological signs and symptoms of dementia, BPSD) in several degenerative dementias, we designed a prospective study of which we here present the baseline data. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with probable Alzheimer's disease (AD) (n = 205), frontotemporal dementia (FTD) (n = 29), mixed dementia (MXD) (n = 39) and dementia with Lewy bodies (DLB) (n = 23) were included. All patients underwent a neuropsychological examination and behavioural assessment by means of a battery of scales (Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). RESULTS: In AD and MXD, activity disturbances and aggressiveness occurred in more than 80% of the patients. With a prevalence of 70%, apathy was very common whereas delusions and hallucinations were rare in FTD patients. Frequently used behavioural assessment scales like the Behave-AD systematically underestimated BPSD in FTD whereas the MFS displayed high sensitivity for frontal lobe symptoms. Hallucinations discriminated DLB patients from other dementias. A high prevalence of disinhibition (65%) in DLB pointed to frontal lobe involvement. CONCLUSIONS: Behavioural assessment may help differentiating between different forms of dementia, further stressing the need for the development of new and more sensitive behavioural assessment scales. By means of the MFS, frontal lobe involvement was frequently observed in DLB. As 70% of FTD patients displayed apathy, prevalence was about two times higher compared to the other disease groups, meanwhile indicating that apathy is frequently observed in dementia, irrespective of its etiology.

Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia.

BACKGROUND: Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study. METHODS: At inclusion, AD (n=152) and FTD (n=28) patients underwent a neuropsychological examination. Behaviour was assessed using a battery of behavioural assessment scales. Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion. RESULTS: In both patient groups, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. No correlations with BPSD were found in the AD patient group. In FTD patients, levels of vitamin B12 were negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). CONCLUSIONS: The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.