The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Cued recall deficits are most closely associated with CSF biomarkers indicative of AD in subjects with MCI. This novel finding complements results from prospective clinical studies and provides further empirical support for cued recall as a specific indicator of prodromal AD, in line with recently proposed research criteria.

An increasing number of longitudinal cohort studies have identified a risk increase for dementia by the chronic use of drugs with anticholinergic properties. The respective data from the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) also showing risk increase (hazard ratio = 2.081) are reported here. The mechanisms by which the risk increase is transported are still unknown. Irritation of compensated alterations of cholinergic transmission at the pre-dementia stage of Alzheimer's disease (AD) or acceleration of neuroinflammation by disturbance of the anti-inflammatory effect of cholinergic innervation are discussed. In terms of dementia prevention, centrally acting anticholinergic drugs should be strictly avoided, because of long-term dementia risk increase in addition to acute negative effects on cognition.

Cognitive functions show large variation in elderly people and are substantially heritable. Animal studies revealed that dynorphins influence cognition and memory, especially in aged animals. Thus, we tested the effect of four SNPs (rs7272891, rs1997794, rs2235751 and rs910080) and the VNTR promoter polymorphism in the prodynorphin gene (PDYN) on episodic memory and verbal fluency in a large (n = 1619) sample of elderly people (mean age: 80 +/- 3.39 years; range 75-90 years) recruited through the German study on ageing, cognition and dementia in primary care patients (AgeCoDe). We found that carriers of the minor alleles of rs1997794 (P < 0.002) and rs910080 (P < 0.005) presented with higher episodic memory scores than homozygote carriers of the major allele. Also, a three marker haplotype including these two SNPs and rs2235751 was associated with better episodic memory scores. Verbal fluency scores were non-significantly better in carriers of these respective alleles. Thus, our results suggest a role of PDYN gene variations in determining memory function also in elderly humans.

No abstract