The subject was a 92-year-old right-handed woman with hypertension but no diabetes mellitus who was a participant in The 90+ Study, a prospective population based study of cognition and longevity in the oldest old. She reported mild shortterm memory loss in 2004 but was still living independently despite blindness in the left eye as a result of shingles.
As part of the Leisure World Cohort Study,12
the participant had completed a health questionnaire in 1984 and followup surveys in 1992 and 1998. These surveys indicated a history of vitamins A and E and ascorbic acid usage for 25 years and estrogen supplementation (1.25 mg) for more than 15 years. The participant indicated that she exercised, on average, 7 hours per week.
Her medical history included hypertension and hypercholesterolemia diagnosed in 1980, a transient ischemic attack in 1990, and atrial fibrillation diagnosed in 1999. Her medications were atenolol, levothyroxine sodium, hydrochlorothiazide, acyclovir, calcium, and potassium chloride. There was a family history of stroke (her brother had a stroke at an unknown age), but no family history of dementia was reported. The participant completed high school and some college. She smoked onefourth pack of cigarettes a day for 17 years, but stopped at age 37 years. No alcohol consumption was reported.
On November 14, 2003, the participant was examined using the Cognitive Abilities Screening Instrument via telephone and scored 33 of a possible 33, indicating intact global cognitive functioning. In 2004, she was examined twice. During these visits, she completed a neuropsychology battery including the MiniMental Status Examination (MMSE); California Verbal Learning Test (9 items); Digit Span (forward and backward) subtest of the Wechsler Adult Intelligence Scale, Third Edition; Boston Naming Test (15 items); animal and letter /F
/ fluency; Constructional Praxis subtest of the Consortium to Establish a Registry for Alzheimer Disease Psychological Battery; and Trail Making Test, parts A through C. The results are given in . Her performance at the first visit was within normal limits for her age group13
on all measured domains including attention, language, visuoconstruction, verbal memory, and executive function. Between visits, in September 2004, the participant had a stroke that resulted in dysarthria, dysphagia, and rightsided weakness for 10 to 14 days. Her performance on the neuropsychological tests administered after the stroke remained within normal limits across domains, with 2 exceptions. Phonemic fluency declined, and she demonstrated mild executive dysfunction as reflected by inability to complete the Trail Making Test, part B. These deficits are best characterized as mild and, on the basis of family reports, did not result in functional loss. The participant died after a second stroke in December 2004.
Neuropsychological Test Scores 6 Months and 1 Month Before Death
At autopsy, the brain weighed 1140 g. Senile plaque formation, which was moderately intense, was predominantly diffuse, although neuritic plaques were readily observed. Neurofibrillary tangle formation, in addition to being present within the hippocampus, subiculum, entorhinal-transentorhinal region, and amygdala, was also seen in moderately severe to severe degree within the frontal, temporal, parietal, and occipital layers of the neocortex (). Overall, the pathological changes were judged to be of stage VI-C severity by Braak and Braak staging criteria (the stage that represents the highest frequency of senile plaques and neurofibrillary tangles). These neuropathologic changes are considered highly likely to be associated with dementia according to criteria of the National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer Disease,14
although our participant did not experience significant cognitive dysfunction. Additional immunostaining () for Aβ and tau proteins was performed to compare findings in our participant with those in a subject without dementia with a similar MMSE score but with few pathologic features of AD (age, 99 years; female sex; MMSE score 28; and Braak and Braak classification III-0) and a subject with dementia with similar neuropathologic features of AD but a much lower MMSE score (age, 94 years; female sex; MMSE score 0; and Braak and Braak classification VI-C). The results showed that senile plaques in our participant's brain were both diffuse and neuritic, compared with only neuritic as observed in the comparison subject with dementia.
Figure 1 The case subject demonstrated neocortical neuropathologic features of Alzheimer disease. At histopathologic analysis, a section of inferior parietal cortex immunostained with polyclonal rabbit antihuman tau (DAKO, Carpenteria, California) showed neuritic (more ...)
Figure 2 Neuropathologic features in the case subject compared with matched control subjects. Note pathologic features in area CA1/subiculum of the hippocampus in the case subject. β-Amyloid deposition is absent in area CA1/subiculum in a 99-year-old woman (more ...)