Anna Di Prima

Systemic Immune Responses in Alzheimer's Disease: In Vitro Mononuclear Cell Activation and Cytokine Production

To investigate the systemic signs of immune-inflammatory responses in Alzheimers disease (AD), in the present study we have analyzed blood lymphocyte subsets and the expression of activation markers on peripheral blood mononuclear cells (PBMCs) from AD patients and age-matched healthy controls (HC) activated in vitro by recombinant amyloid-beta peptide (rAbeta42). Our study of AD lymphocyte subpopulations confirms the already described decrease of the absolute number and percentage of B cells when compared to HC lymphocytes, whereas the other subsets are not significantly different in patients and controls. We report the increased expression of the activation marker CD69 and of the chemokine receptors CCR2 and CCR5 on T cells but no changes of CD25 after activation. B cells are also activated by rAbeta42 as demonstrated by the enhanced expression of CCR5. Moreover, rAbeta42 induces an increased expression of the scavenger receptor CD36 on monocytes. Some activation markers and chemokine receptors are overexpressed in unstimulated AD cells when compared to controls. This is evidence of the pro-inflammatory status of AD. Stimulation by rAbeta42 also induces the production of the pro-inflammatory cytokines IL-1beta, IL-6, IFN-gamma, and TNF-alpha, and of the anti-inflammatory cytokines IL-10 and IL-1Ra. The chemokines RANTES, MIP-1beta, and eotaxin as well as some growth factors (GM-CSF, G-CSF) are also overproduced by AD-derived PBMC activated by rAbeta42. These results support the involvement of systemic immunity in AD patients. However, our study is an observational one so we cannot draw a conclusion about its contribution to the pathophysiology of the disease.

Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer's disease (AD)

Acetylcholinesterase inhibitors (AchEIs) are extensively used in Alzheimers disease (AD) while reality orientation therapy (ROT) is a cognitive rehabilitation indicated for mentally deteriorated patients. We aimed to evaluate the efficacy of the combination of donepezil with an intensive ROT with active participation of the caregiver. Patients with AD (n=100, mean age 78.4±4.3 years) initiated treatment with donepezil, 5mg/day; 62 of them underwent a 3-week, daily ROT and physical reactivation training with the caregiver (Group A); 38 participants received only donepezil therapy (Group B). All subjects were tested for cognitive and functional abilities at baseline, at the end of the training program, and after 2 months of follow-up. There was a significant improvement in mini-mental state examination (MMSE) score (p<0.001) and the AD assessment scale-cognitive (ADAS-Cog) subscale (p<0.001), without changes in impaired activity of daily living (ADL) and instrumental ADL (IADL) after intensive ROT training in Group A. MMSE was maintained after 2 months in-home ROT continuation. There were no significant changes in MMSE in drug-only treated patients (Group B) after 3 weeks, with a non-significant tendency to improvement in ADAS-Cog. Our results suggest benefit of an intensive ROT program in dementia patients receiving donepezil that seems to be maintained as far as ROT is continued by the caregiver.