Transitions to Mild Cognitive Impairments, Dementia, and Death: Findings from the Nun Study

Abstract

The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991-2002) of 470 Nun Study participants aged > or = 75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality.

Reversion from mild cognitive impairment to normal or near-normal cognition

“…For example, in the Nun Study, 14.5% of subjects with MCI returned to normal cognition after 11 years of follow-up. 3 Subjects more often stayed in their current cognitive state than transitioned to another, which was observed among the ADC subjects as well. Both studies may have underestimated the proportion of subjects returning to normal cognition, as clinicians are not blinded to previous patient diagnoses; clinicians may be disinclined to assign a diagnosis of normal cognition for a patient previously diagnosed as MCI.…”

“…1 However, several longitudinal epidemiologic studies have found that transition from an MCI diagnosis back to normal cognition is fairly common. [2][3][4][5][6][7][8][9] Estimates of transition from MCI back to normal cognition have been quite varied, ranging from 4% to 15% [2][3][4][5] in clinic-based studies and 29% to 55% 6 -9 in population-based studies, depending in part on duration of follow-up. To date, few, if any, studies have focused on the subset of subjects who return to normal cognition after an MCI diagnosis.…”

Does cognition predict mortality in midlife? Results from the Whitehall II cohort study

“…In effect, 74% of this association remained unexplained. Memory deficits are critical to the diagnosis of mild cognitive impairment (Brayne, 2007;Gauthier et al, 2006) which is itself linked to progression to dementia (Tschanz et al, 2006;Tyas et al, 2007). More than a half people with mild cognitive impairment progress to dementia within 5 years (Gauthier et al, 2006).…”

The Nun Study

“…The tools used to diagnose intact cognitive status, MCI, and dementia have been described in previous Nun Study publications. 15 Briefly, participants classified as cognitively intact had scores within normal limits on 4 cognitive tests in the neuropsychological battery of CERAD. 16,17 They also had intact global cognitive ability as measured by the MiniMental State Examination (MMSE) 18 and were intact regarding activities of daily living (ADL).…”