George Hoganson

Early and late life cognitive activity and cognitive systems in old age.

Little is known about the relative benefits of cognitively stimulating activities at different points in the lifespan. In a cohort of 576 older persons without dementia, we assessed current and past (childhood, young adulthood, middle age) frequency of cognitive activity; availability of cognitively stimulating resources in the home in childhood and middle age; and 5 domains of cognitive function. Past cognitive activity and cognitive resources were positively correlated with both current cognitive activity and current cognitive function. The association with cognitive function was reduced after controlling for current cognitive activity, however. Current cognitive activity was associated with better cognitive function, especially semantic memory and perceptual speed, even after controlling for past activity. The results suggest that past cognitive activity contributes to current cognition principally through its association with cognitive activity in old age.

Early Life Socioeconomic Status and Late Life Risk of Alzheimer’s Disease

The authors examined the relation of early life socioeconomic status to incident Alzheimer’s disease (AD), level of cognition and rate of cognitive decline in old age. For up to 10 years, 859 older Catholic clergy members without dementia at baseline completed annual clinical evaluations as part of the Religious Orders Study. The evaluations included clinical classification of AD and detailed cognitive testing. At baseline, indicators of early life household socioeconomic level (e.g., parental education) and the county of birth were ascertained. Socioeconomic features of the birth county (e.g., literacy rate) were estimated with data from the 1920 US Census. Composite measures of early life household and community socioeconomic level were developed. In analyses that controlled for age, sex and education, higher household and community socioeconomic levels in early life were associated with higher level of cognition in late life but not with risk of AD or rate of cognitive decline. The results suggest that early life socioeconomic level is related to level of cognition in late life but not to rate of cognitive decline or risk of AD.

Clinical-pathologic study of depressive symptoms and cognitive decline in old age

Objective: To clarify the relationship between depressive symptoms and the clinical and neuropathologic manifestations of dementia. Methods: In a clinical-pathologic cohort study, 1,764 older persons without cognitive impairment at enrollment completed annual clinical evaluations for a mean of 7.8 years. The evaluations included assessment of depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) and cognitive function (battery of 17 performance tests). A total of 582 individuals died during follow-up and underwent a uniform neuropathologic examination to quantify β-amyloid plaques and tau tangle density in multiple brain regions and identify neocortical Lewy bodies, hippocampal sclerosis, and gross and microscopic cerebral infarcts. Results: Level of depressive symptoms slightly increased during follow-up. Incident mild cognitive impairment (52.2%) was associated with higher level of depressive symptoms before the diagnosis but not with change in symptoms after the diagnosis; incident dementia (17.9%) was associated with higher symptom level before dementia onset and with more rapid decline in symptoms after dementia onset. None of the neuropathologic markers was related to level of depressive symptoms or change in symptoms over time. In a mixed-effects model adjusted for the neuropathologic markers, higher level of depressive symptoms averaged over evaluations was associated with more rapid global cognitive decline, accounting for 4.4% of the variability in decline not attributable to the neuropathologic markers. Depressive symptoms did not modify the association of the neuropathologic markers with cognitive decline. Conclusion: In old age, depressive symptoms have an association with cognitive decline that is independent of the neuropathologic hallmarks of dementia.

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.

Acute disseminated encephalomyelitis in 228 patients A retrospective, multicenter US study

Objective: To analyze the range of demographic, clinical, MRI, and CSF features of acute disseminated encephalomyelitis (ADEM), a rare, typically monophasic demyelinating disorder, and analyze long-term outcomes including time and risk factors for subsequent clinical events as well as competing diagnoses. Methods: We performed a retrospective, multicenter study in 4 US academic medical centers of all patients clinically diagnosed with ADEM. Initial presentation of pediatric and adult ADEM and monophasic and multiphasic disease were compared. The Aalen-Johansen estimator was used to produce estimates of the probability of transitioning to a multiphasic diagnosis as a function of time since initial diagnosis, treating death and alternative diagnoses as competing risks. Results: Of 228 patients (122 children, age range 1–72 years, 106 male, median follow-up 24 months [25th–75th percentile 6–67], 7 deaths), approximately one quarter (n = 55, 24%) experienced at least one relapse. Relapsing disease in children was more often diagnosed as multiphasic ADEM than in adults (58% vs 21%, p = 0.007), in whom MS was diagnosed more often. Encephalopathy at initial presentation (hazard ratio [HR] 0.383, p = 0.001), male sex (HR 0.394, p = 0.002), and increasing age at onset (HR 0.984, p = 0.035) were independently associated with a longer time to a demyelinating disease relapse in a multivariable model. In 17 patients, diagnoses other than demyelinating disease were concluded in long-term follow-up. Conclusions: Relapsing disease after ADEM is fairly common and associated with a few potentially predictive features at initial presentation. Age-specific guidelines for ADEM diagnosis and treatment may be valuable, and vigilance for other, mostly rare, diseases is imperative.

Late-life depression is not associated with dementia-related pathology

OBJECTIVE To test the hypothesis that late-life depression is associated with dementia-related pathology. METHOD Older participants (n = 1,965) in 3 longitudinal clinical-pathologic cohort studies who had no cognitive impairment at baseline underwent annual clinical evaluations for a mean of 8.0 years (SD = 5.0). The authors defined depression diagnostically, as major depression during the study period, and psychometrically, as elevated depressive symptoms during the study period, and established their relation to cognitive outcomes (incident dementia, rate of cognitive decline). A total of 657 participants died and underwent a uniform neuropathologic examination. The authors estimated the association of depression with 6 dementia-related markers (tau tangles, beta-amyloid plaques, Lewy bodies, hippocampal sclerosis, gross and microscopic infarcts) in logistic regression models. RESULTS In the full cohort, 9.4% were diagnosed with major depression and 8.6% had chronically elevated depressive symptoms, both of which were related to adverse cognitive outcomes. In the 657 persons who died and had a neuropathologic examination, higher beta-amyloid plaque burden was associated with higher likelihood of major depression (present in 11.0%; OR = 1.392, 95% CI = 1.088, 1.780) but not with elevated depressive symptoms (present in 11.3%; OR = 0.919, 95% CI = 0.726, 1.165). None of the other pathologic markers was related to either of the depression measures. Neither dementia nor antidepressant medication modified the relation of pathology to depression. CONCLUSION The results do not support the hypothesis that major depression is associated with dementia-related pathology.

Internal Carotid Artery Dissection After a Roller Coaster Ride in a 4-Year-Old: Case Report and Review of the Literature

BACKGROUND Strokes associated with roller-coaster rides are unusual. PATIENT A previously healthy 4-year-old boy developed acute onset of left-sided weakness when flying home from a trip to an amusement park. He had frequented two roller coaster rides the day prior. Upon evaluation, he was found to have an acute right middle cerebral artery territory infarction. RESULTS Cerebral angiography showed dissection of the right cervical internal carotid artery and right middle cerebral artery occlusion involving the M1 segment. He was treated with aspirin. Evaluation for underlying connective tissue diseases was unremarkable. CONCLUSION We speculate that repetitive forces of acceleration and deceleration may have led to a cervical internal carotid artery intimal tear, followed by thromboembolism. It remains uncertain what the threshold of susceptibility to repetitive rotational changes and tolerability to G forces in an otherwise healthy child truly is.

Harm avoidance and cerebral infarction

OBJECTIVE Harm avoidance, a trait indicative of behavioral inhibition, is associated with disability and dementia in old age, but the basis of these associations is uncertain. We test the hypothesis that higher level of harm avoidance is associated with increased likelihood of cerebral infarction. METHOD Older persons without dementia completed a standard measure of harm avoidance. During a mean of 3.5 years of follow-up, 257 (of 1,082) individuals died of whom 206 (80%) underwent brain autopsy. The number of chronic cerebral infarcts (microscopic plus gross; expressed as 0, 1, or >1) was assessed on neuropathologic examination, completed in 192 individuals at the time of analyses. RESULTS On postmortem examination, chronic cerebral infarcts were found in 89 (42 with 1, 47 with >1). Higher harm avoidance was associated with higher likelihood of infarcts (odds ratio = 1.083, 95% confidence interval = 1.040-1.128). A moderately high level of the trait (score = 17, 75th percentile) was associated with a 2.4-fold increase in the likelihood of infarction compared with a moderately low level of the trait (score = 6, 25th percentile). These associations persisted in models that controlled for other cardiovascular risk factors. CONCLUSION Higher level of the harm avoidance trait may be a risk factor for cerebral infarction.

Acute disseminated encephalomyelitis in China, Singapore and Japan: a comparison with the USA.

Ethnicity‐related differences in the incidence of acute disseminated encephalomyelitis (ADEM) and other demyelinating diseases including multiple sclerosis and neuromyelitis optica spectrum disorders have been reported. Little is reported on the influence of ethnicity and geographical location in ADEM.