Edythe M. Halligan

Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly

OBJECTIVE To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. DESIGN Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). SETTING University medical center. PARTICIPANTS From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. MAIN OUTCOME MEASURES Regional PiB retention and cognitive test performance. RESULTS Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. CONCLUSIONS Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

Self-Reported Sleep Quality Predicts Poor Cognitive Performance in Healthy Older Adults

This study examined the relation between sleep quality and cognitive performance in older adults, controlling for common medical comorbidities. Participants were community volunteers who, while not selected on the basis of their sleep, did report substantial variability in sleep quality. Good and poor sleepers differed on tests of working memory, attentional set shifting, and abstract problem solving but not on processing speed, inhibitory function, or episodic memory. Poor sleep was also associated with increased depressive symptomatology but only for functional symptoms (e.g., decreased concentration) and not for mood (e.g., sadness). The relationships between sleep quality and cognition were not explained by confound factors such as cerebrovascular disease, depression, or medication usage. Sleep problems may contribute to performance variability between elderly individuals but only in certain cognitive domains.

The Relation of White Matter Hyperintensities to Cognitive Performance in the Normal Old: Education Matters

ABSTRACT This study examined whether the severity of cerebral white matter abnormalities (evident on MR images as white matter hyperintensities (WMH)) was related to the cognitive performance of 141 high-functioning older adults. The elderly showed the typical age decrement on measures of processing speed, working memory, and inhibition; however WMH severity was significantly related only to processing speed. The strength of this relationship was, however, influenced by the educational level of the participants, such that processing speed was more associated with WMH severity in less-educated than in well-educated participants. This is consistent with recent concepts of cognitive reserve, but does raise a question as to the underlying source of the cognitive decrement found in the sort of well-educated elders typically used in cognitive-aging studies.

Serum anticholinergic activity, white matter hyperintensities, and cognitive performance

The authors investigated whether the cognitive impairments associated with white matter hyperintensities (WMH) in normal elderly subjects are exacerbated by any anticholinergic medications being taken by the subjects. Results showed serum anticholinergic activity (SAA) and WMH volume to have a synergistic interaction such that the cognitive decrements associated with increasing WMH volume were greatest in those older individuals in the highest quartile of the SAA distribution.

Sentence Context Influences the Interpretation of Word Meaning by Alzheimer Patients

This study examined whether, in Alzheimer patients, verbal context selectively activates elements of a words meaning that are relevant to the context. Subjects were shown a sentence ending in a target noun, followed by a question about an attribute of that target. The sentence primed either the attribute in the question, a different attribute, or no attribute. Both normals and AD patients answered the question faster when the target had appeared in a context priming that particular attribute. These results suggest that Alzheimer patients retain knowledge of semantic attributes and that these attributes are susceptible to contextual activation.

Cognitive and motor slowing in Alzheimer's disease and geriatric depression

While response slowing on psychological tasks is a symptom of both depression and Alzheimers disease (AD), the underlying mechanisms may be quite different: a slowing of cognitive processing in AD and a motor retardation in depression. This hypothesis was tested by examining the rate at which participants performed a simple cognitive operation: subvocal pronunciation. Participants were shown words of between one and three syllables and were asked to decide whether each word ended in a particular sound. This task required participants to transform the written word into its phonological representation, an operation thought to involve subvocal pronunciation. Decision time rose linearly with the number of syllables in all three subject groups. The linear function of the AD patients had a significantly greater slope, indicating a slower rate of subvocal pronunciation, whereas the slope was the same for the normal old and depressed. Both the depressed and AD patients had a higher intercept than the normal old, suggesting a sensorimotor slowing. After treatment, the intercept of the linear function for depressed patients fell, but there was no change in the slope. Thus, this study suggests that AD produces a slowing in both cognitive and motor processes, whereas depression results solely in a motor retardation.

Cognitive aging in persons with minimal amyloid-β and white matter hyperintensities.

Substantial individual differences exist in the magnitude of the cognitive decline associated with normal aging. Potential contributors to this intersubject variability include white matter hyperintensities (WMH) and preclinical Alzheimers disease, evident as increased brain amyloid. This study examined whether older individuals with minimal evidence of WMH and/or brain amyloid-beta (seen on positron emission tomography with the Pittsburgh compound B radiotracer-PiB) still showed significant cognitive decrements compared to the young. Older individuals, conservatively screened for normal range performance on an extensive neuropsychological battery, underwent structural magnetic resonance imaging (MRI) and PiB scans and performed tests of information processing speed, working memory and inhibitory function. The elderly were divided into PiB(+) and PiB(-) groups based on radiotracer retention. There were no significant differences in cognitive performance between PiB(+) and PiB(-) elderly. However, both PiB groups performed significantly worse than did the young on cognitive testing. WMH burden in the same individuals was quantified by consensus ratings using a 10 point scale with a median split defining two groups, WMH(+) and WMH(-). There were no differences in cognitive performance between WMH(+) and WMH(-) individuals, but both WMH groups performed significantly worse than did the young. Older participants who were both PiB(-) and WMH(-) also performed significantly worse than did the young in all three cognitive domains. The present results suggest that normal-elderly individuals whose brain scans show minimal evidence of amyloid deposition or WMH, still demonstrate a major decrement in comparison to younger persons on measures of processing resources and inhibitory efficiency.

Memory impairment in elderly individuals with a mildly elevated serum TSH: The role of processing resources, depression and cerebrovascular disease

This study examined whether a mild elevation in serum Thyroid Stimulating Hormone (TSH) in normal older individuals was associated with a cognitive impairment. Participants consisted of 15 individuals with a high- TSH level and 82 with a normal TSH. The high-TSH group performed significantly worse than the normal- TSH group on tests of immediate and delayed verbal recall and on the Mini-Mental State Exam. This decrement was not due to group differences in processing resources nor was it explained by comorbid cerebrovascular disease, depression or anticholinergic drug usage. These results suggest that undetected mild thyroid dysfunction may contribute to the cognitive decrements found in older adults.

Contextual constraint facilitates semantic decisions about object pictures by Alzheimer patients.

Semantic constraints produced by sentence context reduce the time normal adults take to decide whether a given stimulus constitutes a meaningful ending to that sentence. The mechanism responsible for this constraint effect is thought to involve generation of featural restrictions based on context. In the present study, participants heard a sentence whose last word was replaced by an object picture. They decided whether the object formed a sensible ending to that sentence. Contextual constraint present in the sentences greatly influenced decision time: the greater the constraint, the faster the decision. Alzheimer patients were as affected by contextual constraint as were normal adults. The normality of the constraint effect in Alzheimer patients suggests that they can generate featural restrictions and thus retain knowledge of the semantic attributes of objects.

Instantiation of semantic categories in sentence comprehension by Alzheimer patients

This study examined whether Alzheimer patients can make elaborative inferences based on the semantic context provided by a sentence. More specifically, if presented with the name of a category in a sentence do they, like normals, infer (instantiate) the particular member of that category most appropriate to the meaning of the sentence (e.g., if a sentence mentions a container of juice, do they infer it is a bottle). Patients were presented with a sentence containing the name of a concrete category. The sense of the sentence was consistent with a low-dominant member of that category. Patients were then shown drawings of four members of that category and asked to select the one appropriate to the sentence. They were later asked to name the drawings. If semantic information is degraded in Alzheimer patients for those objects Alzheimer patients cannot name (as has been claimed), then AD patients should be unable to carry out the type of elaborative semantic inference required to instantiate. Results showed that Alzheimer patients were highly accurate at instantiating even objects they could not name. This is consistent with a relative preservation of semantic knowledge about concrete objects in Alzheimer patients.