Absence of cognitive impairment or decline in preclinical Alzheimer's disease

Objective: To determine whether clinically nondemented elderly individuals with pathologically confirmed preclinical AD are characterized by cognitive decline as measured by psychometric tests before death. Methods: Psychomet ric performance was examined retrospectively in 14 individuals who were non demented at time of death and grouped in accordance with their neuropatholo gic findings: 1) Healthy brain (n = 9) was characterized by the absence of senile plaques or by only patchy neocortical deposits of plaques; 2) precli nical AD (n = 5) was characterized by neuritic and diffuse plaques distribu ted throughout the neocortex. All individuals showed neurofibrillary pathol ogic change in medial temporal lobe structures. For comparison, we also eva luated 10 individuals who died in the earliest symptomatic stage of dementi a of the Alzheimer type (DAT). All individuals had been assessed by clinica l and psychometric measures during life. The psychometric measures yielded a standardized factor score that represented global cognitive performance. Results: At the last assessment before death, individuals with very mild DA T were impaired on the factor score and on individual psychometric measures with respect to the nondemented individuals, Those nondemented individuals with preclinical AD did not differ in performance from those with healthy brains. For individuals with at least three psychometric assessments during life, there was no decline in performance for either those with healthy br ains (n = 5) or preclinical AD (n = 3), although decline was evident for ve ry mild DAT individuals (n = 5). Conclusions: Pathologically confirmed prec linical AD is not associated with cognitive impairment or decline, even on measures shown to be sensitive to very mild DAT.