Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study

Abstract

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.

Figure 1

Neuropathologic comparison of Nun Study participants with Braak stage V–VI pathologic changes and clinical dementia (AD group) to those without dementia (NDAP group). AD indicates Alzheimer disease; NDAP, nondemented with Alzheimer pathologic symptom; NFT, neurofibrillary tangles; NP, neuritic plaques; SP, senile plaques. Mean and SEM are shown. *p < 0.05, AD versus NDAP group.

Figure 2

Neuropsychologic profile comparison of Nun Study participants with Braak stage V–VI pathologic changes and clinical dementia (AD group) to those without dementia (NDAP group). AD indicates Alzheimer disease; BNT, Boston naming test; CNPR, constructional praxis score; NDAP, nondemented with Alzheimer pathology; MMSE, Mini–Mental Status Examination; VRBF, verbal fluency; WRCL, word list recall; WRL, word list memory; WRCO, word recognition. Mean and SEM are shown. *p < 0.05, AD versus NDAP group.

Figure 3

Neuropathologic comparison of Nun Study participants with Braak stage V pathologic changes and clinical dementia (AD group) to those without dementia (NDAP group). AD indicates Alzheimer disease; NDAP, nondemented with Alzheimer pathology; NFT, neurofibrillary tangles; NP, neuritic plaques; SP, senile plaques. Mean and SEM are shown. *p<0.05, AD versus NDAP group.

Figure 4

Neuropsychologic profile comparison of Nun Study participants with Braak stage V pathologic changes and clinical dementia (AD group) to those without dementia (NDAP group). AD indicates Alzheimer disease; BNT, Boston naming test; CNPR, constructional praxis score; NDAP, nondemented with Alzheimer pathologic symptom; MMSE, Mini–Mental Status Examination; VRBF, verbal fluency; WRCL, word list recall; WRL, word list memory; WRCO, word recognition. Mean and SEM are shown. *p < 0.05, AD versus NDAP group.

Figure 5

Neuropathologic comparison of Nun Study participants with Braak stage III–IV pathologic changes and clinical dementia to those without dementia. AD indicates Alzheimer disease; NDAP, nondemented with Alzheimer pathologic symptom; NFT, neurofibrillary tangles; NP, neuritic plaques; SP, senile plaques. Mean and SEM are shown. *p < 0.05, demented versus nondemented groups.

Figure 6

Neuropsychologic profile comparison of Nun Study participants with Braak stage III–IV pathologic changes and clinical dementia to those without dementia. BNT indicates Boston naming test; CNPR, Constructional Praxis score; MMSE indicates Mini–Mental Status Examination; VRBF, verbal fluency; WRCL, word list recall; WRL, word list memory; WRCO, word recognition. Mean and SEM are shown. *p < 0.05, demented versus nondemented group.