Citations

AbstractIntroductionFrontotemporal dementia disorders (FTDs) are heterogeneous phenotypical behavioral and language disorders usually associated with frontal and/or temporal lobe degeneration. We investigated their incidence in a population‐based cohort.MethodsUsing a records‐linkage system, we identified all patients with a diagnostic code for dementia in Olmsted County, MN, 1995–2010, and confirmed the diagnosis of FTD. A behavioral neurologist verified the clinical diagnosis and determined phenotypes.ResultsWe identified 35 FTDs cases. Overall, the incidence of FTDs was 4.3/100,000/year (95% CI: 2.9, 5.7). Incidence was higher in men (6.3/100,000, 95% CI 3.6, 9.0) than women (2.9/100,000; 95% CI: 1.3, 4.5); we observed an increased trend over time (B = 0.83, 95% CI: 0.54, 1.11, P < .001). At autopsy, clinical diagnosis was confirmed in eight (72.7%) cases.DiscussionWe observed an increased incidence and trends of FTDs over time. This may reflect a better recognition by clinicians and improvement of clinical criteria and diagnostic tools.

Abstract Recent study has shown that incident dementia risk is higher among older persons who decline in both cognition and gait. This study assesses whether this relationship exists in multiple other aging populations. Data are from the Baltimore Longitudinal Study of Aging (n=662, 51%women,22%blacks), Health, Aging and Body Composition Study (n=746, 51%women,44%blacks), and Mayo Clinic Study of Aging (n=2771, 48%women,0.3%blacks). Participants were at least 60, initially free of cognitive impairment, dementia, and dismobility (gait speed≤0.6m/s), with repeated measures of verbal memory and gait speed before dementia diagnosis (average follow-up 5.8-12.1 years). Within each cohort, participants were divided into four groups: memory decliners alone, gait decliners alone, dual decliners, or neither (healthy agers). Gait speed decline was defined as a loss of ≥0.05m/sec/year; memory decline was defined as cohort specific bottom slope tertile. Incident dementia risk was examined by Cox regression with healthy agers as reference, adjusted for sex, race, baseline age, gait speed and memory. Across studies, incident dementia ranged from 3% to 17%. Compared to healthy agers, memory decliners alone had 3.4 to 4.3 times higher risk for developing dementia (p&lt;0.01). Gait decliners alone had 2.1-5.6 times higher risk for dementia (p&lt;0.05). Dual decliners had 7.6-10.8 times the risk (p&lt;0.001). Dual decline signifies a more rapid progression to dementia. These consistent findings suggest that dual decliners might be a potentially valuable target group for both preventive interventions and mechanistic studies. Whether dual decline identifies a particular subtype or multiple subtypes of dementia remains to be investigated.

BACKGROUND: We evaluated the hypothesis that the rate of postoperative decline in global cognition is greater in older adults exposed to general anesthesia with nitrous oxide (N 2 O) compared to general anesthesia without N 2 O. METHODS: Longitudinal measures of cognitive function were analyzed in nondemented adults, 70–91 years of age, enrolled in the Mayo Clinic Study of Aging. Linear mixed-effects models with time-varying covariates assessed the relationship between exposure to surgery with general anesthesia (surgery/GA) with or without N 2 O and the rate of long-term cognitive changes. Global cognition and domain-specific cognitive outcomes were defined using z scores, which measure how far an observation is, in standard deviations, from the unimpaired population mean. RESULTS: The analysis included 1819 participants: 280 exposed to GA without N 2 O following enrollment and before censoring during follow-up (median [interquartile range {IQR}] follow-up of 5.4 [3.9–7.9] years); 256 exposed to GA with N 2 O (follow-up 5.6 [4.0–7.9] years); and 1283 not exposed to surgery/GA (follow-up 4.1 [2.5–6.4] years). The slope of the global cognitive z score was significantly more negative following exposure to surgery/GA after enrollment (change in slope of −0.062 [95% confidence interval {CI}, −0.085 to −0.039] for GA without N 2 O, and −0.058 [95% CI, −0.080 to −0.035] for GA with N 2 O, both P < .001). The change in slope following exposure to surgery/GA did not differ between those exposed to anesthesia without versus with N 2 O (estimated difference −0.004 [95% CI, −0.035 to 0.026], P = .783). CONCLUSIONS: Exposure to surgery/GA is associated with a small, but statistically significant decline in cognitive z scores. Cognitive decline did not differ between anesthetics with and without N 2 O. This finding provides evidence that the use of N 2 O in older adults does not need to be avoided because of concerns related to decline in cognition.

Abstract Introduction Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total‐tau [T‐tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging–Alzheimer's Association Research Framework. Methods We examined, in a community‐based population (N = 777, aged 50–95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T‐tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in‐house enzyme‐linked immunosorbent assays. Results Multiple variables were differentially associated with CSF NfL and T‐tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T‐tau had the strongest association with cognition in the presence of amyloidosis, followed by Ng. Variables associations with NfL did not differ by amyloid status. Discussion Understanding factors that influence CSF (N) markers will assist in the interpretation and utility of these markers in clinical practice.

AbstractIntroductionPractical algorithms predicting the probability of amyloid pathology among patients with subjective cognitive decline or mild cognitive impairment may help clinical decisions regarding confirmatory biomarker testing for Alzheimer's disease.MethodsAlgorithm feature selection was conducted with Alzheimer's Disease Neuroimaging Initiative and Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing data. Probability algorithms were developed in Alzheimer's Disease Neuroimaging Initiative using nested cross‐validation accompanied by stratified subsampling to obtain 1000 internally validated decision trees. Semi‐independent validation was conducted using Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. Independent external validation was conducted in the population‐based Mayo Clinic Study of Aging.ResultsTwo algorithms were developed using age and normalized immediate recall z‐scores, with or without apolipoprotein E ε4 carrier status. Both algorithms had robust performance across data sets and when substituting different recall memory tests.DiscussionThe statistical framework resulted in robust probability estimation. Application of these algorithms may assist in clinical decision‐making for further testing to diagnose amyloid pathology.