NACC’s Uniform Data Set (UDS), collected since 2005, is widely regarded as the gold standard by the field. This longitudinal, multi-domain neurocognitive and phenotypic dataset includes robust, criteria-based diagnoses, providing a valuable foundation for grounding other studies. UDS data collection instruments are trusted benchmarks in Alzheimer’s disease and related dementias (AD/ADRD) clinical phenotypic assessments globally.

The Oregon Alzheimer Disease Center is the core program of the Layton Aging & Alzheimer's Disease Center (LAADC), supported by the National Institute on Aging (NIA, NIH). We promote interactive, multidisciplinary research among the scientific community. Our primary emphasis is on studies of preclinical dementia, as well as early dementia. Well-characterized patients, clinical, MRI and genetic data, as well as biological specimens are made available to investigators and research groups worldwide.

National Alzheimer’s Coordinating Center (NACC) uniform dataset characteristics of cases and controls.

ObjectiveTo compare the rate of cognitive and functional decline in dysexecutive, typical and amnestic subgroups of Alzheimer’s disease.Methods943 participants from the National Alzheimer’s Coordinating Center (NACC) database who had a diagnosis of probable AD were followed for a mean of 2.3 years. A dysexecutive subgroup (n = 165) was defined as having executive performance >1.5 SD worse than memory performance, an amnestic subgroup (n = 157) was defined as having memory performance >1.5 SD worse than executive performance and a typical subgroup (n = 621) was defined as having a difference in executive and memory performance of

Objective: To compare the proportion of APOEε4 genotype carriers in aphasic versus amnestic variants of Alzheimer's disease (AD). Method: The proportion of APOEε4 carriers was compared among 3 groups. 1) Forty-two patients with primary progressive aphasia (PPA) and AD pathology (PPA/AD) enrolled in the Northwestern Alzheimer Disease Center Clinical Core. 2) 1,418 patients with autopsy confirmed AD and amnestic dementia of the Alzheimer-type (DAT/AD); 3) 2,608 cognitively normal controls (NC). The latter two groups were compiled from the National Alzheimer Coordinating Center (NACC) database. Logistic regression models analyzed the relationship between groups and APOEε4 carrier status, adjusting for age of onset and sex as needed. Results: Using NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be APOEε4 carriers. Adjusting for sex and age at symptom onset, the DAT/AD group was 2.46 times as likely to be carriers compared to PPA/AD. There was no significant difference in the proportion of APOEε4 carriers for PPA/AD compared to NC. PPA subtypes included 24 logopenic, 10 agrammatic nonfluent, and eight either mixed (n=5) or too severe (n=3) to subtype. The proportion of carriers and non carriers was similar for logopenic and agrammatic subtypes, both having fewer carriers. Conclusion: The proportion of APOEε4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that APOEε4 is an anatomically selective risk factor that preferentially increases the vulnerability to AD pathology of memory-related medial temporal areas rather that language-related neocortices.

APOE4 PPA Supplementary Materials 04-08-19This file contains information about additional data analysis that was completed in response to reviewer's comments but not necessary to include in the manuscript. There are tables reporting the age makeup of the samples and also an analysis using a matched sample technique that showed no differences from the original analysis in which the samples were not matched and sample numbers were uneven.

ObjectiveValidation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed “neuropsychological (NP) decline,” in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum.MethodsA prospective cohort study utilized 6,794 older adults from the National Alzheimer’s Coordinating Center (NACC) database with a baseline diagnosis of normal cognition, impaired without MCI or with MCI. Operationalization of NP decline over 12-month follow-up used regression-based norms developed in a robustly normal reference sample. The extent to which each participant’s 12-month follow-up score deviated from norm-referenced expectations was quantified and standardized to an NP decline z-score. Cox regression evaluated whether the NP decline metric predicted future dementia.ResultsParticipant’s NP decline scores predicted future all-cause dementia in the total sample, χ2 = 110.71, hazard ratio (HR) = 1.989, p < 0.001, and in the subset diagnosed with normal cognition, χ2 = 40.84, HR = 2.006, p < 0.001, impaired without MCI diagnosis, χ2 = 14.89, HR = 2.465, p < 0.001, and impaired with MCI diagnosis, χ2 = 55.78, HR = 1.916, p < 0.001.ConclusionOperationalizing NP decline over 12 months with a regression-based norming method allows for further stratification of dementia risk along the cognitively unimpaired-to-MCI spectrum. The use of NP decline as an adjunctive marker of risk beyond standard cognitive diagnostic practices may aid in prognosis and clinical decision-making.

Identifying factors underlying selective neuronal vulnerability is crucial for understanding Alzheimer's disease (AD) pathophysiology. The Neuromodulatory Subcortical System (NSS) includes nuclei that exhibit early, but varied vulnerability to tau accumulation and neuronal loss. This varied vulnerability represents a valuable opportunity to explore the underlying mechanisms of AD. In this study, we investigated factors contributing to selective neuronal vulnerability by comparing transcriptomic profiles of two similar NSS nuclei with differing vulnerabilities to AD, the locus coeruleus and substantia nigra. Using paired samples from well-characterized postmortem human tissue from individuals in early Braak stages and free of comorbid neuropathologic diagnoses, we identified pathways related to cholesterol homeostasis and antioxidant pathways response as key potential drivers of vulnerability., We leveraged transcriptomics and immunohistochemistry in paired samples from human postmortem tissue representing a vulnerable and resilient region – the locus coeruleus (LC) and substantia nigra (SN). These regions have comparable anatomical features but distinct vulnerability to AD. Participant selection and neuropathologic assessment Cases were sourced from the Biobank for Aging Studies at the University of São Paulo and the Neurodegenerative Disease Brain Bank at the University of California, San Francisco Memory and Aging Center which is an ADRC. Consent for brain donation was obtained from subjects or next of kin following the site-specific protocol approved by the relevant Institutional Review Board and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki. In both brain banks, brain tissue was sampled for neuropathological diagnosis following NACC guidelines. Basic histological and immunohistochemical stains..., , # Data from: Pathways underlying selective neuronal vulnerability in Alzheimer's disease: Contrasting the vulnerable locus coeruleus to the resilient substantia nigra

Immunohistochemistry data, supplementary data, and supplementary methods

https://doi.org/10.5061/dryad.sbcc2frgp

Trancriptomic analysis

Description of the data and file structure

The frozen half of the brainstem for selected cases was kept on dry ice during the dissection. A scalpel was used to shave down the midbrain until the pigmented SN was exposed. An additional 3-5mm of midbrain was shaved down around the rostral portion of the SN, with borders defined by the pigmented area. The protruding portion of the SN was sliced off of the shaved-down face of the midbrain and put into RNAlater (AM7020, Invitrogen) to protect RNA in case of thawing during transport for processing. The sample in RNAlater was frozen down at -80C and transported on dry ice.

The LC was isol..., This dataset is derived from human research subjects who enrolled in a research study approved by a site-specific IRB. Participants, or a next-of-kin, provided informed consent permitting the use of and sharing of de-identified data. All personally identifiable information are removed when data are shared using technical controls approved by the relevant IRB's.

Demographic and clinical characteristics of participants in our samples from the National Alzheimer’s Coordinating Center, the Rotterdam Study, the Framingham Heart Study, and the Sacramento Area Latino Study on Aging.

Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) concentrations identify asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression.

Methods: Baseline plasma NfL concentrations were measured with Simoa in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN and MAPT mutation carriers and non-carriers from the same families were classified by disease severity [asymptomatic, prodromal and full phenotype] using the CDR^® Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR^®+NACC-FTLD). Linear mixed effect models related NfL to clinical variables.

Results: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or subsequent disease progression compared to non-progressors (original: 11.4 ± 7 pg/mL vs. 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs. 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR^®+NACC-FTLD sum of boxes scores, neuropsychological function and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers.

Conclusions: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression, and is a potential tool to select participants for prevention clinical trials.

Classification of evidence: This study provides Class I evidence that in familial FTLD, elevation of plasma NfL predicts short-term risk of clinical progression.

In each of the three scenarios the ample size N is 2,000 and we used 50 simulation runs to estimate C-index and IBS. The mean value and the 90% confidence interval are also reported in the table.

The mean value and the 90% confidence interval are reported here, over 50 independent simulation runs.

Additional file 14. Summary statistics of NACC data analyses. (A, B) Subject information for MMSE models comparing (A) imipramine and other antidepressants or (B) olanzapine and other antipsychotics, including age, sex, baseline MMSE score, and drug exposure time. (C, D) Subject information for clinical diagnosis reversion models comparing (C) imipramine and other antidepressants or (D) olanzapine and other antipsychotics, including age, sex, baseline MMSE score, drug exposure time, number of subjects with reversions, and number of reversions per subject. (E, F) Subject information for clinical diagnosis conversion models comparing (E) imipramine and other antidepressants or (F) olanzapine and other antipsychotics, including age, sex, baseline MMSE score, drug exposure time, number of subjects with conversions, and number of conversions per subject. (G, H) Subject information for multiple medications models comparing (G) imipramine, doxepin, fluoxetine, citalopram, and all other antidepressants or (H) olanzapine, aripiprazole, quetiapine, and all other antipsychotics, including age, sex, baseline MMSE score, drug exposure time, number of subjects with reversions, and number of reversions per subject. (I) Complete test statistics and degrees of freedom for all statistical tests.