Age-Correction of Test Scores Reduces the Validity of Mild Cognitive Impairment in Predicting Progression to Dementia

Objectives

A phase of mild cognitive impairment (MCI) precedes most forms of neurodegenerative dementia. Many definitions of MCI recommend the use of test norms to diagnose cognitive impairment. It is, however, unclear whether the use of norms actually improves the detection of individuals at risk of dementia. Therefore, the effects of age- and education-norms on the validity of test scores in predicting progression to dementia were investigated.

Methods

Baseline cognitive test scores (Syndrome Short Test) of dementia-free participants aged ≥65 were used to predict progression to dementia within three years. Participants were comprehensively examined one, two, and three years after baseline. Test scores were calculated with correction for (1) age and education, (2) education only, (3) age only and (4) without correction. Predictive validity was estimated with Cox proportional hazard regressions. Areas under the curve (AUCs) were calculated for the one-, two-, and three-year intervals.

Results

82 (15.3%) of initially 537 participants, developed dementia. Model coefficients, hazard ratios, and AUCs of all scores were significant (p<0.001). Predictive validity was the lowest with age-corrected scores (−2 log likelihood  = 840.90, model fit χ² (1)  = 144.27, HR  = 1.33, AUCs between 0.73 and 0.87) and the highest with education-corrected scores (−2 log likelihood  = 815.80, model fit χ² (1)  = 171.16, HR  = 1.34, AUCs between 0.85 and 0.88).

Conclusion

The predictive validity of test scores is markedly reduced by age-correction. Therefore, definitions of MCI should not recommend the use of age-norms in order to improve the detection of individuals at risk of dementia.     

Histochemical detection and image analysis of non-specific esterase activity and the amount of polyphenols during annual bud development in Norway spruce

The study focused on Norway spruce trees during their annual development and, specifically, on the histochemical analysis of the activity of the non-specific esterase and the amount of polyphenols in the vegetative buds. Azo-coupling reaction with naphthol-AS-acetate as a substrate and Fast Blue B Salt as a coupling reagent was applied to the longitudinal median cryo-sections of the formalin-fixed buds. A method of image analysis was developed to evaluate the intensity of the histochemical reaction quantitatively. High activity of non-specific esterase was detected in the cells of the collenchymatic plate, the youngest bud scales, the leaf primordia, in the zone of differentiation of vascular tissues and procambium of the dormant bud. The activity of non-specific esterase decreased in all tissues during bud break. During the growth of a new shoot enzyme activity was detected only in the vascular bundles of the shoot. Enzyme activity re-occurred at the beginning of the autumn in the cells of the collenchymatic plate of the newly establishing buds. Three different types of polyphenols at different intracellular localizations (as verified by scanning electron microscopy) were observed: granular, vacuolar and drop-like polyphenols. The amount and localization of those polyphenols changed during the bud growing cycle. The positive reaction of all three types of polyphenols are tannin in nature. These findings are discussed from the viewpoint of frost tolerance and tissue differentiation.