Knopman, David S.

AbstractBackground: hearing loss has been associated with mild cognitive impairment (MCI) and dementia. Studies have not assessed whether hearing difficulties (HD) that interfere with daily activities as reported by partners can be a marker for increased risk for cognitive decline and impairment.Objective: to assess the cross-sectional and longitudinal associations between informant-based HD, which interfere with daily activities and the risk for MCI and dementia.Methods: the study included 4812 participants without dementia, enrolled in the Mayo Clinic Study of Aging (mean age (SD) 73.7 (9.6) years) with cognitive evaluation and informant-based report on participant’s HD that interfere significantly with daily activities at baseline and for every 15 months. Cox proportional hazards models (utilising time-dependent HD status and age as the time scale) were used to examine HD and the risk for MCI or dementia, and mixed-effects models (allowing for random subject-specific intercepts and slopes) were used to examine the relationship between HD and cognitive decline.Results: about, 981 participants had HD and 612 (12.7%) had prevalent MCI at baseline; 759 participants developed incident MCI and 273 developed incident dementia. In cognitively unimpaired participants at baseline, those with HD had higher risk for MCI (hazard ratio [HR] = 1.29, 95% confidence interval [CI] (1.10, 1.51), P = 0.002; adjusting for sex, years of education). In participants without dementia, those with HD had higher risk for dementia (HR: 1.39, 95% CI, (1.08–1.79), P = 0.011; adjusting sex and education). In individuals with MCI, HD was associated with modestly greater cognitive decline.Conclusions: informant-based HD was associated with increased risk for MCI and dementia.

OBJECTIVE We sought to examine associations in older adults among diabetes, glycemic control, diabetes duration, and biomarkers of hyperglycemia with incident mild cognitive impairment (MCI) and incident dementia. RESEARCH DESIGN AND METHODS We conducted a prospective analysis of 5,099 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended the fifth (2011–2013) exam. Cognitive status was assessed during follow-up via telephone calls, death certificate codes, surveillance, and a follow-up examination (2016–2017). We defined incident cognitive impairment as incident MCI or incident dementia in persons dementia-free at the index examination; we also examined each outcome separately. Diabetes was defined using self-report, medications, or HbA1c ≥6.5%; poor glycemic control in persons with diabetes was defined as HbA1c ≥7%. We examined the following biomarkers of hyperglycemia: HbA1c, fructosamine, glycated albumin, and 1,5-anhydroglucitol. RESULTS Mean age at baseline was 76 years, 59% were female, and 21% were black. Diabetes (hazard ratio [HR] 1.14 [95% CI 1.00, 1.31]), poor glycemic control in persons with diabetes (HR 1.31 [95% CI 1.05, 1.63]), and longer diabetes duration (≥5 vs. <5 years; HR 1.59 [95% CI 1.23, 2.07]) were significantly associated with incident cognitive impairment. We found a J-shaped association between HbA1c and incident dementia. Glycated albumin and fructosamine were also associated with incident dementia, independently of HbA1c. HbA1c and fructosamine were also associated with incident MCI. CONCLUSIONS Diabetes status, poor glycemic control, and longer diabetes duration were associated with worse cognitive outcomes over a median follow-up of 5 years.

ABSTRACT BACKGROUND AND PURPOSE The objective of this study was to longitudinally investigate the trajectory of change in 1 H MRS measurements in asymptomatic MAPT mutation carriers who became symptomatic during follow‐up, and to determine the time at which the neurochemical alterations accelerated during disease progression. METHODS We identified eight MAPT mutations carriers who transitioned from asymptomatic to symptomatic disease during follow‐up. All participants were longitudinally followed with an average of 7.75 years (range 4‐11 years) and underwent two or more single voxel 1 H MRS examinations from the posterior cingulate voxel, with a total of 60 examinations. The rate of longitudinal change for each metabolite was estimated using linear mixed models. A flex point model was used to estimate the flex time point of the change in slope. RESULTS The decrease in the NAA/mI ratio accelerated 2.09 years prior to symptom onset, and continued to decline. A similar trajectory was observed in the presumed glial marker mI/Cr ratio accelerating 1.86 years prior to symptom onset. CONCLUSIONS Our findings support the potential use of longitudinal 1 H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.

Abstract Introduction Neuroimaging biomarkers are important for early diagnosis of Alzheimer's disease, and comparing multimodality neuroimaging to autopsy data is essential. Methods We compared the pathologic findings from a prospective autopsy cohort (n = 100) to Pittsburgh compound B PET (PiB‐PET), 18 F‐fluorodeoxyglucose PET (FDG‐PET), and MRI. Correlations between neuroimaging biomarkers and neuropathologic schemes were assessed. Results PiB‐PET showed strong correlations with Thal amyloid phase and Consortium to Establish a Registry for Alzheimer's Disease score and categorized 44% of Thal phase 1 participants as positive. FDG‐PET and MRI correlated modestly with Braak tangle stage in Alzheimer's type pathology. A subset of participants with “none” or “sparse” neuritic plaque scores had elevated PiB‐PET signal due to diffuse amyloid plaque. Participants with findings characterized as “suspected non‐Alzheimer's pathophysiology” represented 15% of the group. Discussion PiB‐PET is associated with Alzheimer's disease, neuritic plaques, and diffuse plaques. FDG‐PET and MRI have modest correlation with neuropathologic schemes. Participants with findings characterized as suspected non‐Alzheimer's pathophysiology most commonly had primary age‐related tauopathy.