Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

OBJECTIVE: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. METHOD: [¹8F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. RESULTS: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. CONCLUSION: 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.

The assessment of changes in cognitive functioning: age-, education-, and gender-specific reliable change indices for older adults tested on the CERAD-NP battery: results of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe).

OBJECTIVES: The Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological (CERAD-NP) battery represents a commonly used neuropsychological instrument to measure cognitive functioning in the elderly. This study provides normative data for changes in cognitive function that normally occur in cognitively healthy individuals to interpret changes in CERAD-NP test scores over longer time periods. DESIGN: Longitudinal cohort study with three assessments at 1.5-year intervals over a period of 3 years. SETTING: : Primary care medical record registry sample. PARTICIPANTS: As part of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients, a sample of 1,450 cognitively healthy general practitioner patients, age 75 years and older, was assessed. MEASUREMENTS: Age-, education-, and gender-specific Reliable Change Indices (RCIs) were computed for a 90% confidence interval for selected subtests of the CERAD-NP battery. RESULTS: Across different age, education, and gender subgroups, changes from at least six to nine points in Verbal Fluency, four to eight points in Word List Memory, two to four points in Word List Recall, and one to four points in Word List Recognition indicated significant (i.e. reliable) changes in CERAD-NP test scores at the 90% confidence level. Furthermore, the calculation of RCIs for individual patients is demonstrated. CONCLUSIONS: Smaller changes in CERAD-NP test scores can be interpreted with only high uncertainty because of probable measurement error, practice effects, and normal age-related cognitive decline. This study, for the first time, provides age-, education-, and gender-specific CERAD-NP reference values on the basis of RCI methods for the interpretation of cognitive changes in older-age groups.

Anticholinergic drug use and risk for dementia: target for dementia prevention.

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.

Gene polymorphisms in prodynorphin (PDYN) are associated with episodic memory in the elderly.

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.