Effect of ApoE epsilon4 allele on visual evoked potentials and resultant flow coupling in patients with Alzheimer.

The apolipoprotein E epsilon4 (ApoE epsilon4) allele is a strong susceptibility factor for Alzheimer disease, which promotes neurodegeneration and cerebrovascular dysfunction. To address this issue in more detail, we simultaneously obtained visual evoked potentials and resultant hemodynamic responses in newly diagnosed Alzheimer patients without signs of vascular lesions on a cerebral magnetic resonance imaging (MRI) scan. Patients were grouped according to ApoE genotype (n = 19 ApoE epsilon4 carrier and n = 12 noncarrier). ApoE epsilon4 carrier had significantly longer peak latencies and a trend to higher interpeak latencies of late potential components. Potential amplitudes and hemodynamic responses were similar in both groups. At the incidental stage of disease process, it appears that the ApoE epsilon4 allele mainly promotes neuronal dysfunction rather than aggravates neurovascular dysfunction. Studies with larger patient samples are warranted to corroborate the first findings.

Does a cognitive-training programme improve the performance of middle-aged employees undergoing in-patient psychosomatic treatment?

PURPOSE: With the ever-increasing average life expectancy and rising age of retirement, cognitive and work capacities in advanced age take on great importance. Cognitive impairments, however, increase with age. The effect of cognitive-training programmes on people with mild cognitive impairment has not been verified in any systematic investigations. METHOD: This study presents a cognitive-training programme designed for middle-aged employees that was implemented and evaluated at the Psychosomatic Clinic Bad Neustadt/Saale in an AB study design (A: no intervention; B: intervention). RESULTS: Memory performance of the intervention group (n = 33) improved significantly between intake and discharge, compared with that of the control group (n = 40), as did self-ratings of memory and work-related attitudes. CONCLUSIONS: A cognitive-training programme is useful and effective in patients with mild cognitive impairment. Future studies should investigate how older or more severely impaired patients benefit from such a programme.

Activation-flow coupling differentiates between vascular and Alzheimer type of dementia.

The activation-flow coupling describes a mechanism, which adapts local cerebral blood flow in accordance with the underlying neuronal activity. It was suggested that the mechanism helps in differentiation between Alzheimer and vascular type of dementia. We combined EEG and Doppler techniques and assessed integrity of the activation-flow coupling in the occipital cortex utilizing a visual stimulation task. Alzheimer patients (MMSE: 18+/-8 points, DemTect 5+/-4 points) without signs of vascular lesions on a MRI scan and vascular demented patients (MMSE: 20+/-6 points, DemTect 6+/-3 points; MRI Fazekas score 7+/-3 points) were compared with data from an age-matched control group. Evoked flow velocity responses in the posterior cerebral artery were analysed according to a control system model specifying the parameters gain, attenuation, natural frequency and rate time. Evoked potentials were analysed for the N(75)-P(100) amplitude difference. Vascular demented patients exhibited a significant decreased gain parameter and increased attenuation parameter indicating severe cerebrovascular dysfunction. Also, the potential amplitudes were significantly decreased indicating neuronal damage due to the vascular disease process. Alzheimer patients did not differ in parameters as compared to the control group supporting other reports of intact occipital function at this stage of disease. Simultaneous assessment of electrical as well as vascular integrity might help in differentiating the most frequent forms of dementia.

Acetylcholine esterase inhibitor donepezil improves dynamic cerebrovascular regulation in Alzheimer patients.

BACKGROUND: Alzheimer's disease (AD) leads to a degeneration of the nucleus basalis of Meynert and thus to decreased cholinergic tonus in the brain. The transcription of endothelial nitric oxide synthase depends on an adequate cholinergic innervation of microvessels and vasoregulative abnormalities have been reported in AD. We investigated activation-flow coupling to study the role of acetylcholine esterase inhibition (AChEI) on vasoregulative function. METHODS: A functional transcranial Doppler approach was used to measure the visually evoked flow velocity response in the posterior cerebral artery in AD patients who had no vascular risk factors. The diagnosis of AD was made according to the ICD10/DSMIIIR-criteria. After baseline recording the effect of four weeks 5mg donepezil and then four weeks 10 mg was investigated. Doppler data were evaluated with a control system approach to obtain dynamic properties of vasoregulation and were compared with a healthy control group. RESULTS: AD patients showed an increased damping (0.64 +/- 0.2; p = 0.007 vs. control) in evoked responses and lower resting flow velocity levels (40 +/- 13 cm/s; p = 0.06 vs. control), which were restored in a dose-dependent manner under AChEI (0.4 +/- 0.2; 44 +/- 11 cm/s). CONCLUSIONS: AD is associated with a functional vasoregulative deficit possibly due to decreased levels of the endothelial nitric oxide synthase. Augmenting levels with AChEI normalized flow regulation possibly leading to a better blood supply to active neurons.

Neurovascular coupling in Alzheimer patients: effect of acetylcholine-esterase inhibitors.

Dualistic effects of acetylcholine-esterase inhibitors on neuronal as well as vasoregulative function have been debated. This study investigated for the first time effects of medication on both components. Visually evoked potentials and resultant hemodynamic responses were assessed in Alzheimer patients (n=31) without vascular lesions in a MRI scan and compared to controls (n=20). After baseline recordings (AD0) tests were repeated under 2x1.5 to 2x3mg (AD1) and 2x4.5 to 2x6mg (AD2) rivastigmine/d. Long-term effects were investigated under 6 months of medication (AD2L). The ADAS, MMSE and DEMTECT were used to assess cognitive function at AD0, AD2 and AD2L. Improvement in vasoregulative function was independent from changes in evoked potentials. Acetylcholine-esterase inhibitors demonstrate substantial vascular effects in humans, which are independent from changes in neuronal function.