Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer’s disease. We have treated 3 patients with Alzheimer’s disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.

This study aims to compare patient- and proxy-rated utilities and health-related quality of life from individuals in different stages of Alzheimer disease (AD). Two hundred seventy-two patients and their primary caregivers were enrolled in a prospective observational study and underwent three consecutive interviews, 6 months apart. Average Mini-Mental State Examination (MMSE) scores were 19.3, 18.0, and 16.4 at the three interviews; scores ranged from 0 to 30. Using the EuroQoL EQ-5D instrument, patient-rated health utilities were on average 0.833 with little variation across MMSE-based severity levels. Proxy-rated health utilities were 0.69 (MMSE >25), 0.64 (MMSE 21-25), 0.50 (MMSE 15-20), 0.49 (MMSE 10-14), and 0.33 (MMSE <10). Proxy-rated utilities, as well as changes in utilities over time, were significantly related to MMSE scores and inversely related to scores on a brief version of the neuropsychiatric inventory (NPI) and institutionalization. Utilities were highly correlated with the disease-specific quality of life instrument QoL-AD. The study shows that the EuroQoL can be used to rate utilities in Alzheimer disease, but there are important differences between patient- and proxy-ratings.

AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA (and EPA), which were associated with reduced release of IL-1beta, IL-6, and granulocyte colony-stimulating factor from PBMCs. This trial was registered at clinicaltrials.gov as NCT00211159.

Mild cognitive impairment (MCI) is sometimes a transition between normal aging and dementia. We investigated the occurrence of MCI in a population referred to a memory clinic. The criteria used to diagnose the state were similar to those used by Petersen et al. in many previous publications. A clinical evaluation after approximately 3 years was also performed. In a subsample of 43 subjects, we found that, during 1 year, 37% (136/402) of all investigated subjects were patients with MCI. After a mean follow‐up time of 3 years, 11% (5/43) showed cognitive improvement, while 53% (23/43) were stable and showed no cognitive decline or improvement. Fifteen out of 42 patients (35%) deteriorated and were diagnosed as demented during the same time. We conclude that MCI is a heterogeneous concept and that the outcome at follow‐up is dependent on which population is studied and how MCI has been defined.