Evaluation neuroprotektiver Strategien am Beispiel ausgewählter neurodegenerativer Erkrankungen: Amyotrophe Lateralsklerose und Alkoholabhängigkeit

Aims: The hippocampus (HC) is characterized by high vulnerability to noxious influence, but also by a considerable regenerative potential. Although deficits in HC-related functions are among the most commonly reported cognitive sequelae in alcoholism, little and conflicting information is available concerning regeneration upon abstinence. The present study has been designed to evaluate (i) the frequency of measurable dysfunction in so called HC tests and (ii) its predictive value for risk to relapse in a cohort of 50 severely affected chronic alcoholic patients and (iii) to monitor recovery of HC-related functions upon strict abstention from alcohol. Methods: Patients underwent a 2-year neuropsychological follow-up including HC-associated tests (Verbal Learning Test, VLT; Nonverbal Learning Test, NVLT; ‘City Map Test’ of Learning and Memory Test, LGT-3), as well as tests of intelligence and attention in the framework of OLITA (Outpatient Long-Term Intensive Therapy for Alcoholics), a programme with careful abstinence monitoring. Results: At study entry, 30/50 (60%) alcoholics had HC dysfunction which tended to predict a lower long-term abstinence probability (P = 0.058). Of the subgroup that could be followed under conditions of strictly monitored alcohol abstinence (n = 32; age 44.7 ± 6.2 years; 23 men, 9 women), 53% (17/32) exhibited distinct HC dysfunction at inclusion which returned to normal after 2 years. Patients with initially normal HC function (9/32) and patients with additional brain damage of different aetiologies (6/32) failed to show improvement on HC-related tests. While the former displayed stably normal HC test performance, the latter remained on a performance level below normal. Conclusions: Demonstrating slow but remarkable regeneration of HC functions upon strict abstention from alcohol, our data strongly support abstinence-oriented long-term treatment of alcoholics. The absence of functional recovery in patients with additional causes of brain damage might be explained by the ‘dual hit’ exhausting the regenerative potential of the HC.