Increased T-cell reactivity and elevated levels of CD8+ memory T-cells in Alzheimer's disease-patients and T-cell hyporeactivity in an Alzheimer's disease-mouse model: implications for immunotherapy.

Neuroinflammation is observed in neurodegenerative diseases like Alzheimer's disease (AD). However, a little is known about the mechanisms of neural-immune interactions. The involvement of peripheral T-cell function in AD is still far from clear, though it plays an important role in immunotherapy. The aim of this study was to determine peripheral T-cell reactivity in AD patients and in an AD mouse model. Mitogenic activation via ligation of the T-cell receptor (TCR) with PHA-L was measured in T lymphocytes from AD patients and Thy1(APP 751SL) x HMG(PS1 M146L)-transgenic mice (APP x PS1). In order to uncover failures in TCR signaling, the TCR was also bypassed by PMA and ionomycin treatment. All patients were sporadic late onset cases and the transgenic mice expressed no mutant APP in lymphocytes, so that direct interactions of mutant APP on T-cell function can be excluded. CD4+ and CD8+ T-cell showed increased reactivity (tyrosine phosphorylation, CD69 expression, and proliferation) in AD, while APP x PS1 transgenic mice displayed hyporeactive CD8+ T-cells after TCR ligation. Increased levels of CD8+ T memory cells and down regulation of CD8 receptor were found in AD and the animal model. Anergic TCR uncoupling was associated with loss of MAPK signaling (p38, ERK1 and ERK2) in APP x PS1. Our data implicate the generation of reactive memory T-cell in AD and of anergic memory T-cells in transgenic mice and should be taken into concern when designing immunotherapy.

No effects of a combination of caregivers support group and memory training/music therapy in dementia patients from a memory clinic population.

OBJECTIVES: To evaluate the impact of a combination of caregiver support group and memory training/music therapy in dementia patients on behavioural and psychological symptoms (BPSD) and caregiver burden compared to a control group. METHOD: Eighteen patient-carer-dyads in the treatment group and 18 patient-carer-dyads as controls were studied in the setting of a memory clinic of a psychiatric university hospital over a period of 2 years. Controls were matched for age, gender, diagnosis, dementia severity, living arrangement and medication. The interventions were conducted once per week for 1 hour run by a clinical psychogeriatric team. Outcome measures were patients' cognitive and functional status as well as BPSD and caregivers subjective burden and depression measured by validated scales. Data were obtained 6, 12 and 24 months after baseline. RESULTS: There were no significant differences between the intervention and control group neither after 6, 12 nor after 24 months treatment. CONCLUSIONS: The lack of a positive impact in alleviating caregiver burden or BPSD after intensive psychological interventions may result from extensive care in the routine clinical management including individual counselling for patients and families. The effect of 'treatment as usual' needs to be taken into account when comparing an intervention and control group, as well as the dosage of the intervention.

Psychometric properties of Clock Drawing Test and MMSE or Short Performance Test (SKT) in dementia screening in a memory clinic population.

OBJECTIVE: To evaluate five different scoring methods of the Clock Drawing Test (CDT) and to examine whether a combination of Mini Mental State Examination (MMSE) or Short Performance Test (Syndrom Kurz Test, SKT), respectively, with CDT can be used for cognitive screening. METHODS: Retrospective blinded analysis of clock drawing performance using five scoring methods (Shulman et al. (1986), Sunderland et al. (1989), Wolf-Klein et al. (1989), Watson et al. (1997), Manos (1997)). A Memory Clinic at an academic psychiatric hospital (University of Frankfurt am Main, Germany). 123 consecutive patients (79 dementia patients, 44 controls). Inter-rater reliability and correlation of five different scoring methods of the CDT with established psychometric tests. Sensitivity and specificity of all five CDT's using the original and modified cut-off scores. Sensitivity, specificity and positive and negative predictive value of a combination of the CDT with MMSE and SKT, respectively. RESULTS: All scoring methods of the CDT showed a highly significant interrater reliability (0.82 to 0.94). Correlation with the MMSE and the SKT was also significant (p < 0.01) for all five CDTs. Highest sensitivity was achieved by the Shulman scoring method (81% sensitivity, specificity 79%). Sensitivity of all scoring methods could be improved up to 89% by modifying the originally proposed cut-off scores at the cost of lower specificity. By combining the CDT with the MMSE or the SKT, respectively, the sensitivity of each of the tests could be improved to 92% (SKT and Shulman scale). In patients with mild dementia (GDS 3), a combination of the Shulman Scale with the SKT (92%) and the MMSE (75%) achieved the highest sensitivity. CONCLUSIONS: The CDT in combination with the MMSE or SKT is an easily administered, non threatening and highly sensitive screening test for dementia in the setting of a memory clinic.