Pupillary cholinergic hypersensitivity predicts cognitive decline in community dwelling elders.

Previous research demonstrated that it is possible to distinguish patients with probable Alzheimer's disease from age-matched controls based on an exaggerated pupil dilation response to dilute tropicamide. The research reported here employed a prospective longitudinal design to follow over time (2-4 years) a sample of 55 community dwelling elders with and without an exaggerated pupil response using the pupil assay and a comprehensive battery of neuropsychological tests sensitive to pre-clinical AD. Discrete time survival modeling was used to assess the ability of the assay to predict a pattern of cognitive decline consistent with early AD. Analysis showed that there is an increased risk (odds ratio of 3) with a hypersensitive pupil response (>/=13% increase in pupil diameter over baseline diameter) for developing significant cognitive impairment in areas of memory attention and language in a pattern, consistent with pre-clinical Alzheimer's disease. When controlling for ApoE allele type the odds ratio for pupil response as a risk factor increased to 4. The analysis also found that an exaggerated pupil response was a significant (p=.02) predictor of cognitive decline. This analysis of longitudinal data has shown that over time an exaggerated response on the pupil assay is a significant independent risk factor for developing pre-clinical Alzheimer's disease. The risk for developing pre-clinical Alzheimer's disease is increased four-fold.

Age-related differences in novelty and target processing among cognitively high performing adults.

Previous research on age-related changes in ERP components in response to novel and target stimuli has not carefully controlled for differences in level of cognitive status between age groups, which may have contributed to the common findings of increased P3 latency, decreased P3 amplitude, and altered P3 scalp distribution. Here, cognitively high-performing (top third based on published norms) old, middle-aged, and young adults matched for IQ, education, and gender participated in a novelty oddball paradigm. There were no age-associated differences in P3 latency. Older adults had a larger, more anteriorly distributed P3 amplitude to all stimulus types, even repetitive standards, suggesting they may rely on increased resources and effortful frontal activity to successfully process any kind of visual stimulus. However, after controlling for this non-specific age-related processing difference, the amplitude and scalp distribution of the P3 component to novel and target stimuli were comparable across age groups, indicating that for cognitively high functioning elders there may be no age-related differences specific to the processing of novel and target events as indexed by the P3 component.

Memory and emotions for the september 11, 2001, terrorist attacks in patients with Alzheimer's disease, patients with mild cognitive impairment, and healthy older adults.

National traumatic events can produce extremely vivid memories. Using a questionnaire administered during telephone interviews, the authors investigated emotional responses to, and memory for. the September 11, 2001, terrorist attacks in patients with Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and healthy older adults in the initial weeks following the event and again 3-4 months later. There were several notable findings. First, patients with AD showed less memory than patients with MCI and older adults. Second, patients with AD, but not patients with MCI or older adults, appeared to retain more memory for personal versus factual information. Third, patients with AD and older adults did not differ in the intensity of their reported emotional responses to the attacks, whereas patients with MCI reported relatively less intense emotional responses. Last, distortions of memory for personal information were frequent for all participants but were more common in patients with AD.

Use of IQ-adjusted norms to predict progressive cognitive decline in highly intelligent older individuals.

Identifying high-functioning older individuals in preclinical phases of Alzheimer's disease (AD) may require more sensitive methods than the standard approach. The authors explored the utility of adjusting for premorbid intelligence to predict progressive cognitive decline or Mild Cognitive Impairment (MCI) in 42 highly intelligent older individuals. When scores were adjusted for baseline IQ, 9 participants had executive impairments, 11 had memory impairments, and 22 scored in the normal range. None were impaired according to standard age norms. Three and a half years later, 9 participants with IQ-adjusted memory impairment declined in naming, visuospatial functioning, and memory; 6 convened to MCI. Three participants with normal memory declined. Implications for using IQ-adjusted norms to predict preclinical AD are discussed.

Loss of calbindin-D28k from aging human cholinergic basal forebrain: relation to neuronal loss.

Cholinergic neurons of the basal forebrain (BFCN) are selectively vulnerable in neurodegenerative disorders of the elderly, particularly in Alzheimer's disease (AD). We investigated age-related changes in the BFCN that may serve as a substrate for this vulnerability. We report a substantial and selective age-related loss of the calcium binding protein calbindin-D(28K) (CB) from the human BFCN. Unbiased stereological estimation indicated that, in individuals under age 65 years, 72% of the choline acetyltransferase (ChAT)-positive BFCN contained CB immunoreactivity. In individuals over age 65 years, only 28% of the BFCN contained CB immunoreactivity, a dramatic loss of 61%. Similar results were obtained using neuronal counts from matching single- or double-stained sections in a larger cohort. The loss of CB immunoreactivity was neurochemically specific. No age-related changes were observed in the number of ChAT- or low-affinity nerve growth factor receptor (p75(NTR))-immunoreactive profiles. The loss of CB was greatest in very old individuals, in whom a small loss of BFCN was observed. Furthermore, the loss of CB displayed the same pattern as the loss of BFCN in AD and was more substantial in the posterior compared with the anterior BFCN sector, suggesting a role for CB in the selective vulnerability of BFCN in AD. The depletion of CB from the BFCN is likely to deprive these neurons of the capacity to buffer high levels of intracellular Ca(2+) and thus to leave them vulnerable to pathological processes, such as those in neurodegenerative disorders, which can cause increased intracellular Ca(2+), thus leading to their degeneration.