Neuropsychiatric symptoms in dementia-a role for neuroinflammation?

Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a relationship between neuroinflammation and neuropsychiatric symptoms in AD in which anti-inflammatory signalling by IL-10 is beneficial from a mental health perspective.

Galantamine versus risperidone for agitation in people with dementia: a randomized, twelve-week, single-center study.

AIMS: To examine the effects of galantamine and risperidone on agitation in patients with dementia. METHODS: A total of 100 patients with dementia and neuropsychiatric symptoms (mean age ± SD: 78.6 ± 7.5 years; 67% female) were included in this 12-week, randomized, parallel-group, controlled, single-center trial. The participants received galantamine (n = 50; target dose: 24 mg) or risperidone (n = 50; target dose: 1.5 mg) for 12 weeks. RESULTS: Both galantamine and risperidone treatment resulted in reduced agitation. However, risperidone showed a significant advantage over galantamine both at week 3 (mean difference in total Cohen-Mansfield Agitation Inventory score: 3.7 points; p = 0.03) and at week 12 (4.3 points; p = 0.01). CONCLUSIONS: Agitation improved in both groups, even if the treatment effects were more pronounced in the risperidone group; however, the effects on cognition and other aspects of tolerability were stronger with galantamine.

Galantamine versus risperidone treatment of neuropsychiatric symptoms in patients with probable dementia: an open randomized trial.

OBJECTIVE: To examine the effects of galantamine and risperidone on neuropsychiatric symptoms in dementia (NPSD) and global function. METHODS: Using a randomized, controlled and open-blind, one-center trial at an in- and outpatient clinic at a university hospital, we studied 100 adults with probable dementia and NPSD. Participants received galantamine (N = 50, target dose 24 mg) or risperidone (N = 50, target dose 1.5 mg) for 12 weeks. The primary outcome was effects on NPSD assessed by the Neuropsychiatric Inventory (NPI). Secondary measures included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating, Clinical Global Impression, and Simpson Angus scales. All tests were performed before and after treatment. RESULTS: Outcome measures were analyzed using analysis of covariance. Ninety-one patients (67% women, mean age 79 ± 7.5 years) with initial NPI score of 51.0 (± 25.8) and MMSE of 20.1 (± 4.6) completed the trial. Both galantamine and risperidone treatments resulted in improved NPSD symptoms and were equally effective in treating several NPI domains. However, risperidone showed a significant treatment advantage in the NPI domains irritation and agitation, F(1, 97) = 5.2, p = 0.02. Galantamine treatment also ameliorated cognitive functions where MMSE scores increased 2.8 points compared with baseline (95% confidence interval: 1.96-3.52). No treatment-related severe side effects occurred. CONCLUSIONS: These results support that galantamine, with its benign safety profile, can be used as first-line treatment of NPSD symptoms, unless symptoms of irritation and agitation are prominent, where risperidone is more efficient.

To be a good food provider: an exploratory study among spouses of persons with Alzheimer's disease.

Large proportions of people with dementia live at home and need help from a relative. The aim of the current study was to examine how people living with persons with Alzheimer's disease (AD) perceived everyday life aspects of food choices, cooking, and food-related work. The analyses are based on focus group interviews including women and men acting as caregivers to people with AD and living in Sweden. The main results identified from the data, were how cohabitants to persons with AD struggle with either taking on a new role as a food provider or extending it, but also how they tried to cope as carer, which entailed food being an important part of the treatment of the disease. Those expressing greatest concern were those perceiving themselves as inexperienced food providers and carers, which in this study were all men.