Relation between frontal lobe symptoms and dementia severity within and across diagnostic dementia categories.

BACKGROUND: To study frontal lobe symptoms in relation to dementia severity within and across diagnostic dementia categories, a cross-sectional analysis of behavioural data was performed. METHODS: Patients with probable Alzheimer's disease (AD) (n = 456), frontotemporal dementia (FTD) (n = 55) and dementia with Lewy bodies (DLB) (n = 48) were included. Dementia severity and frontal lobe symptoms were assessed by means of the global deterioration scale and the Middelheim frontality score (MFS). RESULTS: In FTD, no difference in MFS total scores between patients belonging to the mild and severe dementia stages was found (p = 0.828). In AD and DLB groups, significantly higher MFS total scores were found in severe dementia stages compared to mild dementia stages (p < 0.001). Comparing MFS total scores between FTD and AD patients, significantly higher scores were achieved in FTD patients, irrespective of dementia severity (p < 0.001). CONCLUSIONS: In FTD patients, frontal lobe symptoms were severe in the mild, moderate and severe dementia stages although the nature of frontal lobe symptoms depended on disease severity. AD and DLB patients displayed more frontal lobe symptoms in the advanced disease stages as compared to disease onset, suggesting gradual frontal lobe involvement as the disease progresses. The nature of frontal lobe symptoms related to dementia severity differed between AD, DLB and FTD patients, suggesting different patterns of frontal lobe involvement. Last but not the least, these data point to the potential diagnostic value of behavioural observation of frontal lobe symptoms for (differential) dementia diagnosis, especially at the earliest disease stages. These findings await confirmation through a prospective, longitudinal study.

Is the geriatric depression scale a reliable screening tool for depressive symptoms in elderly patients with cognitive impairment?

OBJECTIVE: To determine the reliability of the 30-item Geriatric Depression Scale (GDS-30) for the screening of depressive symptoms in dementia and mild cognitive impairment (MCI) using the Cornell Scale for Depression in Dementia (CSDD) as the 'gold standard'. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with MCI (n = 156) and probable Alzheimer's disease (AD) (n = 247) were included. GDS-30, CSDD, Mini Mental State Examination (MMSE) and Global Deterioration Scale were assessed in all patients at inclusion. The AD group was divided in three subgroups: mild AD (MMSE>or=18) (n = 117), moderate AD (MMSE< 18 and >or=10) (n = 89) and severe AD (MMSE<10) (n = 38). RESULTS: In MCI patients, moderate but highly significant correlations were found between GDS-30 and CSDD scores (Pearson: r = 0.565; p < 0.001). In mildly (r = 0.294; p = 0.001), moderately (r = 0.273; p = 0.010) and severely (r = 0.348; p = 0.032) affected AD patients, only weak correlations between GDS-30 and CSDD scores were calculated. ROC curve analysis showed that sensitivity and specificity values of respectively 95% and 67% were achieved when a GDS-30 cut-off score of 8 was applied in MCI patients. In AD patients, too low sensitivity and specificity values did not allow selecting an optimal cut-off score by means of ROC curve analysis. CONCLUSION: Using the CSDD as 'gold standard', we demonstrated that the GDS-30 is a reliable screening tool for depressive symptoms in MCI but not in AD patients.

The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia.

To identify neurochemical correlates of behavioral and psychological signs and symptoms of dementia (BPSD), we set up a prospective study. Patients with probable Alzheimer's disease (AD) (n=181), mixed dementia (MXD) (n=28), frontotemporal dementia (FTD) (n=25) and dementia with Lewy bodies (DLB) (n=24) were included. At inclusion, all patients underwent lumbar puncture, neuropsychological examination and behavioral assessment (battery of behavioral assessment scales). Cerebrospinal fluid (CSF) levels of norepinephrine and of (nor)epinephrine (MHPG), serotonin (5HIAA) and dopamine (DOPAC, HVA) metabolites were determined by HPLC and electrochemical detection. Spearman Rank-Order followed by Bonferroni correction was used for calculating correlations. In FTD patients, CSF norepinephrine levels were positively correlated with dementia severity (r=0.539; p=0.021). CSF DOPAC levels were correlated with BPSD in general (r=0.537; p=0.007), associated caregiver burden (r=0.567; p=0.004) and agitated and aggressive behavior (r=0.568; p=0.004). In a subgroup of FTD patients who did not receive psychotropic pharmacological treatment, a strong correlation between CSF HVA/5HIAA ratios (reflecting serotonergic modulation of dopaminergic neurotransmission) and aggressive behavior (r=0.758; p=0.009) was found. In MXD patients, (verbally) agitated behavior was positively associated with the turnover of norepinephrine (r=0.633; p=0.002). No significant correlations were found in AD and DLB groups. In FTD, increased activity of dopaminergic neurotransmission and altered serotonergic modulation of dopaminergic neurotransmission is associated with agitated and aggressive behavior respectively. This study demonstrated that neurochemical mechanisms underlying the pathophysiology of BPSD are both BPSD-specific and disease-specific which might have implications for future development of new and more selective pharmacological treatments of BPSD.

Differentiation between dementia and depression among older persons: can the difference between actual and premorbid intelligence be useful?

We wanted to investigate whether the difference between actual and premorbid intelligence can be useful to make an early differentiation between Alzheimer's disease (AD) and depression among elderly. A Dutch version of the National Adult Reading Test (NLV), a measure of premorbid IQ and the Raven Coloured Progressive Matrices (RCPM), a measure of actual intelligence were administered to patients with mild (34) and moderate (27) AD, depressed elderly (36) and healthy control subjects (51). Logistic regression analyses revealed that intellectual decline (i.e. subtracting NLV percentile score from RCPM percentile score) was only able to predict group membership when moderate AD patients were compared to depressed and healthy individuals. Our results indicate that intellectual decline may not be a concomitant of elderly depression. However, the differentiation between mild AD and elderly depression can not be made by means of the difference between premorbid (NLV) and actual (RCPM) intelligence scores.