Aß (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts.

BACKGROUND AND PURPOSE: There is increasing recognition of the importance of cortical microinfarcts to overall brain health, cognition, and Alzheimer dementia. Cerebral small vessel pathologies are associated with microinfarcts and frequently coexist with Alzheimer disease; however, the extent to which Aß (amyloid beta) and tau pathology modulates microvascular pathogenesis is not fully understood. Study objective was to examine the relationship of small vessel pathologies, arteriolosclerosis, and cerebral amyloid angiopathy, with cortical microinfarcts in people with differing levels of Aß or tau tangle burden. METHODS: Participants were 1489 autopsied older people (mean age at death, 89 years; 67% women) from 1 of 3 ongoing clinical-pathological cohort studies of aging. Neuropathological evaluation identified cortical Aß and tau tangle burden using immunohistochemistry in 8 brain regions, provided semiquantitative grading of cerebral vessel pathologies, and identified the presence of cortical microinfarcts. Logistic regression models adjusted for demographics and atherosclerosis and examined whether Aß or tau tangle burden modified relations between small vessel pathologies and cortical microinfarcts. RESULTS: Cortical microinfarcts were present in 17% of older people, moderate-to-severe cerebral amyloid angiopathy pathology in 36%, and arteriolosclerosis in 34%. In logistic regression models, we found interactions with Aß and tau tangles, reflecting that the association between arteriolosclerosis and cortical microinfarcts was stronger in the context of greater Aß (estimate, 0.15; SE=0.07; P=0.02) and tau tangle burden (estimate, 0.13; SE=0.06; P=0.02). Interactions also emerged for cerebral amyloid angiopathy, suggesting that the association between cerebral amyloid angiopathy and cortical microinfarcts is more robust in the presence of higher Aß (estimate, 0.27; SE=0.07; P<0.001) and tangle burden (estimate, 0.16; SE=0.06; P=0.005). CONCLUSIONS: These findings suggest that in the presence of elevated Aß or tangle pathology, small vessel pathologies are associated with greater microvascular tissue injury, highlighting a potential link between neurodegenerative and vascular mechanisms.

Apolipoprotein E and change in episodic memory in blacks and whites.

BACKGROUND: Apolipoprotein E (APOE) ε4 is related to faster decline in episodic memory in Whites, but the relation is unknown in Blacks. The purpose of this study was to determine whether ε4 has a selective effect on decline in episodic memory in Blacks. METHODS: Data are from two cohort studies with similar design. The sample consisted of 1,211 participants [28.4% Blacks, mean age = 78.6 years (SD = 7.4), education = 14.7 years (SD = 3.1)] without dementia at baseline, who underwent annual clinical evaluations for up to 6 years. Summary measures of 5 cognitive abilities were derived from 18 neuropsychological tests. RESULTS: In mixed models that controlled for age, sex, education, and race, possession of ε4 (present in 32.9% of Blacks and 21.0% of Whites, p < 0.001) was related to faster decline in episodic memory and 4 other cognitive abilities (all p values <0.01). In separate models that examined the interaction of race and ε4 on decline, there was no significant difference between Blacks and Whites in the effect of ε4 on decline in episodic memory, perceptual speed, or visuospatial ability. By contrast, the effect of ε4 differed for semantic memory and working memory. Results were similar after adjusting for vascular conditions. CONCLUSIONS: The results suggest that APOE ε4 is related to a faster rate of decline in episodic memory in Blacks similar to Whites. In addition, there were racial differences in the effect of ε4 in other cognitive abilities such that the ε4 allele was related to faster decline in semantic memory and working memory for Whites but not for Blacks.

Perceived discrimination and cognition in older African Americans.

Existing evidence suggests that psychosocial stress is associated with cognitive impairment in older adults. Perceived discrimination is a persistent stressor in African Americans that has been associated with several adverse mental and physical health outcomes. To our knowledge, the association of discrimination with cognition in older African Americans has not been examined. In a cohort of 407 older African Americans without dementia (mean age = 72.9; SD = 6.4), we found that a higher level of perceived discrimination was related to poorer cognitive test performance, particularly episodic memory (estimate = -0.03; SE = .013; p < .05) and perceptual speed tests (estimate = -0.04; SE = .015; p < .05). The associations were unchanged after adjusting for demographics and vascular risk factors, but were attenuated after adjustment for depressive symptoms (Episodic memory estimate = -0.02; SE = 0.01; Perceptual speed estimate = -0.03; SE = 0.02; both p's = .06). The association between discrimination and several cognitive domains was modified by level of neuroticism. The results suggest that perceived discrimination may be associated with poorer cognitive function, but does not appear to be independent of depressive symptoms. (JINS, 2012, 18, 1-10).

Premorbid reading activity and patterns of cognitive decline in Alzheimer disease.

BACKGROUND: Educational and occupational attainment have been associated with progression of Alzheimer disease in some studies. One hypothesis about this association is that education and occupation are markers for lifelong participation in cognitively stimulating activities like reading. OBJECTIVE: To assess the relation of premorbid reading activity with patterns of cognitive decline in Alzheimer disease. METHODS: During a 4-year period, 410 persons with Alzheimer disease had annual clinical evaluations, which included administration of 17 cognitive function tests from which global, verbal, and nonverbal summary measures were derived. At baseline, a knowledgeable informant was questioned about the affected person's reading frequency and access to reading materials before dementia onset. RESULTS: A composite measure of premorbid reading activity was developed. It had moderately high internal consistency and was positively correlated with education and baseline level of cognitive function. In analyses that controlled for baseline cognitive function, education, and other demographic variables, higher level of premorbid reading activity was associated with more rapid decline on the global cognitive and verbal measures but not on the nonverbal measure. CONCLUSIONS: These results suggest that both the extent and nature of premorbid cognitive experiences may affect how Alzheimer disease pathology is clinically expressed.

Natural history of mild cognitive impairment in older persons.

BACKGROUND: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. METHODS: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. RESULTS: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. CONCLUSIONS: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.

Depressive symptoms, cognitive decline, and risk of AD in older persons.

BACKGROUND: Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. METHODS: Participants are Catholic clergy members who were aged > or =65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. RESULTS: At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. CONCLUSIONS: The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.

Object-based attention and object working memory: overlapping processes revealed by selective interference effects in humans.

Human observers can discriminate two attributes from the same object more efficiently than attributes from two different objects even if the retinal locations of the attributes are the same in the single and dual object cases. The single object advantage challenges the spatial spotlight view of attention and suggests that attentional selection can be object based. We report that the single object advantage is reliably reduced when an object working memory task is performed concurrently, whereas concurrent verbal and spatial working memory tasks have no effect. This selective interference effect provides support for the existence of object-based attentional processes that also contribute to the short-term retention of objects in working memory. These results are consistent with the hypothesis that both attentional and memory subsystems are organized along domain-specific lines, and suggest the importance of attention in rehearsal operations. The contributions of inferior temporal and parietal mechanisms that have been implicated in attending to and remembering objects are considered.

Spatial characteristics of cerebral polyopia: a case study.

A 41-year-old woman showed bilateral monocular polyopia and an incomplete, right-sided homonymous hemianopia following bilateral cerebral strokes confirmed by neuroimaging. She was tested with briefly-presented visual stimuli to determine whether her polyopic images varied with visual field position of stimuli which evoked them. Stimuli close to her scotoma elicited polyopic images at shorter latency and higher probability than did stimuli more distant from it. RS could maintain stable fixation on small stimuli, suggesting that eye movements were not responsible for her polyopia. We discuss the possibility that cerebral polyopia is due to recoding of visual receptive fields in primary visual cortex and that bilateral occipital lesions are a causative factor in the genesis of the disorder.

Cognitive decline in incident Alzheimer disease in a community population.

OBJECTIVE: To measure the cognitive consequences of incident Alzheimer disease (AD) in older African American and white subjects. METHODS: Data are from the Chicago Health and Aging Project, a longitudinal cohort study of older white and black persons residing in a geographically defined community. At 3-year intervals, the entire study population completed 4 brief cognitive tests, from which a previously established composite measure of global cognition was derived, and a subset underwent detailed clinical evaluation that supported clinical classification of mild cognitive impairment, dementia, and AD. We used mixed-effects models to examine change in cognitive function following the diagnostic evaluation. RESULTS: On clinical evaluation, 614 persons were found to have no cognitive impairment, 395 had mild cognitive impairment, and 149 had AD (88.5% mild); 10 persons with other dementias were excluded from analyses. During up to 11 years of observation following the clinical evaluation (mean = 5.5, SD = 2.5), the composite measure of global cognition declined a mean of 0.042 unit per year (SE = 0.008, p < 0.001) in those with no cognitive impairment. In comparison to the no cognitive impairment group, the annual rate of decline was increased more than twofold in mild cognitive impairment (estimate = 0.086, SE = 0.011, p < 0.001) and more than fourfold in AD (estimate = 0.173, SE = 0.020, p < 0.001). Results did not reliably vary by race, sex, or age. CONCLUSIONS: Alzheimer disease has a devastating impact on cognition, even in its prodromal stages, with comparable effects in African American and white persons.

Temporal course of depressive symptoms during the development of Alzheimer disease.

OBJECTIVE: To characterize change in depressive symptoms before and after the onset of dementia in Alzheimer disease (AD). METHOD: We used data from the Chicago Health and Aging Project, a longitudinal cohort study of risk factors for AD in a geographically defined population of old people. Two subsets were analyzed. In 357 individuals who developed incident AD during the study, self-report of depressive symptoms (Center for Epidemiologic Studies Depression Scale) was obtained at 3-year intervals for a mean of 8 to 9 years. In 340 individuals who agreed to annual data collection, informant report of depressive symptoms (Hamilton Depression Rating Scale) was obtained for a mean of 3 years after a diagnosis of AD (n = 107), mild cognitive impairment (n = 81), or no cognitive impairment (n = 152). RESULTS: The incident AD group reported a barely perceptible increase in depressive symptoms during 6 to 7 years of observation before the diagnosis (0.04 symptoms per year) and no change during 2 to 3 years of observation after the diagnosis except for a slight decrease in positive affect. In those with annual follow-up, neither AD nor its precursor, mild cognitive impairment, was associated with change in informant report of depressive symptoms during a mean of 3 years of observation. CONCLUSION: Depressive symptoms show little change during the development and progression of AD to a moderate level of dementia severity.

Cognitive activity and the cognitive morbidity of Alzheimer disease.

OBJECTIVE: To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter. METHODS: As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals. RESULTS: On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale. CONCLUSION: Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.

Educational attainment and cognitive decline in old age.

BACKGROUND: Level of education is a well-established risk factor for Alzheimer disease but its relation to cognitive decline, the principal clinical manifestation of the disease, is uncertain. METHODS: More than 6,000 older residents of a community on the south side of Chicago were interviewed at approximately 3-year intervals for up to 14 years. The interview included administration of four brief tests of cognitive function from which a previously established composite measure of global cognition was derived. We estimated the associations of education with baseline level of cognition and rate of cognitive change in a series of mixed-effects models. RESULTS: In an initial analysis, higher level of education was related to higher level of cognition at baseline, but there was no linear association between education and rate of change in cognitive function. In a subsequent analysis with terms to allow for nonlinearity in education and its relation to cognitive decline, rate of cognitive decline at average or high levels of education was slightly increased during earlier years of follow-up but slightly decreased in later years in comparison to low levels of education. Findings were similar among black and white participants. Cognitive performance improved with repeated test administration, but there was no evidence that retest effects were related to education or attenuated education's association with cognitive change. CONCLUSIONS: The results suggest that education is robustly associated with level of cognitive function but not with rate of cognitive decline and that the former association primarily accounts for education's correlation with risk of dementia in old age.

Memory complaints are related to Alzheimer disease pathology in older persons.

OBJECTIVE: To study the relationship between Alzheimer disease (AD) pathology and memory complaints proximate to death. METHODS: A group of 90 older persons underwent detailed clinical evaluations and brain autopsy at death. The evaluations included administration of questions on subjective memory complaints and clinical classification of dementia and AD. On postmortem examination, neuritic plaques, diffuse plaques, and neurofibrillary tangles in tissue samples from five cortical regions were counted, and a summary measure of overall AD pathology was derived. In addition, amyloid load and tau tangles were quantified in eight regions. RESULTS: In multiple linear regression models adjusted for age, sex, and education, memory complaints were associated with AD pathology, including both amyloid and tau tangles. Subsequent analyses demonstrated that the relationship between memory complaints and AD pathology was present in those with and without dementia, and could not be explained by the potentially confounding effects of depressive symptoms or coexisting common chronic health problems. CONCLUSION: Memory complaints in older persons may indicate self awareness of a degenerative process.

Proneness to psychological distress and risk of Alzheimer disease in a biracial community.

Persons without dementia residing in a biracial community completed a brief scale of proneness to psychological distress, and 1,064 were subsequently examined for incident Alzheimer disease (AD) 3 to 6 years later. In analyses controlling for selected demographic and clinical variables, persons prone to distress were 2.4 times more likely to develop AD than persons not distress prone. This effect was substantially stronger in white persons compared to African Americans.

The psychologizing of Chinese healing practices in the United States.

This paper explores ways in which Chinese healing practices have undergone acculturation in the United States since the early 1970s. Reacting to what is perceived as biomedicine's focus on the physiological, those who describe themselves as favoring a holistic orientation often use the language of "energy blockage" to explain illness, whether thought of as "physical," "emotional," or "spiritual." Acupuncture in particular has been appropriated as one modality with which to "unblock" such conditions, leading to its being used by some practitioners in conjunction with more psychotherapeutic approaches which include valuing the verbalizing of feelings. Some non-Chinese practitioners in the United States, returning to older Chinese texts to develop "an American acupuncture," are reinserting diagnoses eliminated from Traditional Chinese Medicine (TCM) by the People's Republic of China as "superstition." The assumption has been that many such diagnostic categories refer to psychological or spiritual conditions, and therefore may be useful in those American contexts which favor this orientation. Among these categories are those drawn from traditions of demonology in Chinese medicine. What was once a religious category in China turns psychological in the American setting. At the same time, many who use these terms have, since the late 1960s, increasingly conflated the psychological and the religious, the latter being reframed as "spiritual." Thus, this indigenization of Chinese practices is a complex synthesis which can be described as simultaneously medical, psychotherapeutic, and religious.

Fadiman and beyond--the dangers of extrapolation.

Cross-cultural patient care is an issue that challenges healthcare providers. Caring for patients who reject some biomedical treatments because of religious or cultural reasons requires knowledge of that person's beliefs for effective treatment. This essay looks at several case studies involving Hmong patients and the way the medical staff reacted to treatment difficulties because of cultural and religious conflicts with surgery. The dangers of universalizing communication methods are stressed.

Effects of warning signals and fixation point offsets on the latencies of pro- versus antisaccades: implications for an interpretation of the gap effect.

The present study was designed to evaluate whether fixation point offsets have the same effects on the average latencies of prosaccades (responses towards target) and antisaccades (responses away from target). Gap and overlap conditions were run with and without an acoustic warning signal. The 'gap effect' was taken to be the difference in mean reaction time between gap and overlap trials. This effect was dramatically reduced by the presentation of the warning signal. Without this signal, fixation offsets can serve as warning signals themselves, which artifactually inflates the magnitude of the gap effect. The warning effect of fixation offsets was equivalent for pro and antisaccades. A significant gap effect is still evident with the acoustic warning signal; however, in this case it is associated primarily with prosaccades. These results replicate and extend our previous work demonstrating that, if their warning effects are controlled, the facilitatory effects of fixation point offsets are response dependent, and suggesting the existence of a component process (fixation release) which is closely linked with the processing architecture underlying target-directed saccades.

Spirituality, religion, and pediatrics: intersecting worlds of healing.

Religious practices such as prayer represent the most prevalent complementary and alternative therapies in the United States. However, biomedicine has sometimes viewed faith and related religious worldviews as relevant only when they obstruct implementation of scientifically sound biomedical care. Recent efforts to arrive at a new synthesis raise challenges for pediatricians. This article reviews theories of child faith development, and models of child spirituality from different disciplinary perspectives. It provides sources illustrating how spirituality and religion may inform children's lives; play a part in children's moral formation, socialization, and induction into a sacred worldview; and provide the child with inner resources. It also suggests some of the positive and negative effects of spiritual and religious engagement. Second, this article examines aspects of spirituality and religion that parents may bring to bear in relation to their children's health. Third, this article addresses the spiritual and/or religious identity of the provider. These topics are discussed in the context of cultural competence and the related importance of religious diversity. The authors suggest 1) some approaches for appropriate inclusion of spirituality in clinical practice, 2) challenges for medical education, and 3) areas requiring further research.