TAR DNA-binding protein 43 and pathological subtype of Alzheimer's disease impact clinical features.

Objective: The aim of this study was to determine whether the frequency of TAR DNA-binding protein 43 (TDP-43) deposition in Alzheimer's disease (AD) differs across pathologically defined AD subtypes (hippocampal sparing [HpSp]; typical and limbic) and further examine the relationship between TDP-43, pathological subtype, and clinical features in AD.

Methods: We identified all cases with pathologically confirmed AD (NIA-Reagan intermediate-high probability, Braak stage IV-VI) independent of cognitive status (n = 188). Neurofibrillary tangle counts were performed using thioflavin-S microscopy in hippocampus and three neocortical regions, and all cases were subtyped: HpSp AD pathology (n = 19); typical AD pathology (n = 136); and limbic AD pathology (n = 33).

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory.

Incidence of dementia among participants and nonparticipants in a longitudinal study of cognitive aging.

Although rates of incident dementia have been reported from several populations, the impact of nonparticipation on dementia incidence in studies of cognitive aging is unknown. In 2004, investigators with the Mayo Clinic Study of Aging selected persons aged 70-89 years from an enumeration of all Olmsted County, Minnesota, residents (age- and sex-stratified random sample). Of 4,398 potential participants, 2,050 agreed to undergo an in-person health assessment.

TDP-43 is a key player in the clinical features associated with Alzheimer's disease.

The aim of this study was to determine whether the TAR DNA-binding protein of 43 kDa (TDP-43) has any independent effect on the clinical and neuroimaging features typically ascribed to Alzheimer's disease (AD) pathology, and whether TDP-43 pathology could help shed light on the phenomenon of resilient cognition in AD. Three-hundred and forty-two subjects pathologically diagnosed with AD were screened for the presence, burden and distribution of TDP-43. All had been classified as cognitively impaired or normal, prior to death.

Association of type 2 diabetes with brain atrophy and cognitive impairment.

Objective: We investigated the associations of diabetes and hypertension with imaging biomarkers (markers of neuronal injury and ischemic damage) and with cognition in a population-based cohort without dementia.

Methods: Participants (n = 1,437, median age 80 years) were evaluated by a nurse and physician and underwent neuropsychological testing. A diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia was made by an expert panel.

Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal.

Objective: To estimate rates of progression from mild cognitive impairment (MCI) to dementia and of reversion from MCI to being cognitively normal (CN) in a population-based cohort.

Methods: Participants (n = 534, aged 70 years and older) enrolled in the prospective Mayo Clinic Study of Aging were evaluated at baseline and every 15 months to identify incident MCI or dementia.

Results: Over a median follow-up of 5.

Practice effects and longitudinal cognitive change in normal aging vs. incident mild cognitive impairment and dementia in the Mayo Clinic Study of Aging.

The objective of this study was to examine practice effects and longitudinal cognitive change in a population-based cohort classified as clinically normal at their initial evaluation. We examined 1390 individuals with a median age of 78.1 years and re-evaluated them up to four times at approximate 15-month intervals, with an average follow-up time of 5 years.

MRI and MRS predictors of mild cognitive impairment in a population-based sample.

Objective: To investigate MRI and proton magnetic resonance spectroscopy (MRS) predictors of mild cognitive impairment (MCI) in cognitively normal older adults.

Methods: Subjects were cognitively normal older adults (n = 1,156) who participated in the population-based Mayo Clinic Study of Aging MRI/MRS study from August 2005 to December 2010 and had at least one annual clinical follow-up. Single-voxel MRS was performed from the posterior cingulate gyri, and hippocampal volumes and white matter hyperintensity volumes were quantified using automated methods.

Mild cognitive impairment due to Alzheimer disease in the community.

Objective: The newly proposed National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer disease (AD) suggest a combination of clinical features and biomarker measures, but their performance in the community is not known.

Methods: The Mayo Clinic Study of Aging (MCSA) is a population-based longitudinal study of nondemented subjects in Olmsted County, Minnesota. A sample of 154 MCI subjects from the MCSA was compared to a sample of 58 amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) to assess the applicability of the criteria in both settings and to assess their outcomes.

Evaluation of memory endophenotypes for association with CLU, CR1, and PICALM variants in black and white subjects.

Background: Genetic variants at the CLU, CR1, and PICALM loci associate with risk for late-onset Alzheimer's disease (LOAD) in genomewide association studies. In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in black and white subjects.

Methods: We pursued an association study between single nucleotide polymorphism genotypes at the CLU, CR1, and PICALM loci and memory endophenotypes.

Association of diabetes with amnestic and nonamnestic mild cognitive impairment.

Background: Type 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD)-related and vascular pathology and may also increase the risk of nonamnestic MCI (naMCI) through vascular disease mechanisms. We examined the association of type 2 diabetes with mild cognitive impairment (MCI) and MCI subtype (aMCI and naMCI) overall and by sex.

Methods: Participants were Olmsted County, Minnesota residents (70 years and older) enrolled in a prospective, population-based study.

Cardiac disease associated with increased risk of nonamnestic cognitive impairment: stronger effect on women.

Objective: To investigate the association of cardiac disease with amnestic and nonamnestic mild cognitive impairment (aMCI and naMCI, respectively). Nonamnestic mild cognitive impairment, a putative precursor of vascular and other non-Alzheimer dementias, is hypothesized to have a vascular etiology.

Design: A prospective, population-based, cohort study with a median 4.

Assessing the temporal relationship between cognition and gait: slow gait predicts cognitive decline in the Mayo Clinic Study of Aging.

Background: The association between gait speed and cognition has been reported; however, there is limited knowledge about the temporal associations between gait slowing and cognitive decline among cognitively normal individuals.

Methods: The Mayo Clinic Study of Aging is a population-based study of Olmsted County, Minnesota, United States, residents aged 70-89 years. This analysis included 1,478 cognitively normal participants who were evaluated every 15 months with a nurse visit, neurologic evaluation, and neuropsychological testing.

Clinical and electrophysiologic variability in amyotrophic lateral sclerosis within a kindred harboring the C9ORF72 repeat expansion.

Our objective was to characterize the motor neuron disease features within a large c9FTD/ALS kindred. We analyzed clinical, electrophysiologic and neuropathologic data in a c9FTD/ALS kindred of Scandinavian ancestry. Results showed that of six family members affected, three had only ALS, two had FTD and one had FTD and ALS.

An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease.

Objective: A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We performed a preliminary assessment of these guidelines.

Methods: We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis, and (18) fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration.

Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study.

Objective: Rapid eye movement sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies), and Parkinson disease (PD). There are no data on such risks in a population-based sample.

Reliable change on the Boston naming test.

Serial assessments are commonplace in neuropsychological practice and used to document cognitive trajectory for many clinical conditions. However, true change scores may be distorted by measurement error, repeated exposure to the assessment instrument, or person variables. The present study provides reliable change indices (RCI) for the Boston Naming Test, derived from a sample of 844 cognitively normal adults aged 56 years and older.

Diagnostic validity of age and education corrections for the Mini-Mental State Examination in older African Americans.

Objectives: To investigate whether demographic (age and education) adjustments for the Mini-Mental State Examination (MMSE) attenuate mean score discrepancies between African-American and Caucasian adults and whether demographically adjusted MMSE scores improve the diagnostic classification accuracy of dementia in African-American adults over unadjusted MMSE scores.

Design: Cross-sectional study.

Setting: Community-dwelling adults participating in the Mayo Clinic Alzheimer's Disease Patient Registry and Alzheimer's Disease Research Center.

Engaging in cognitive activities, aging, and mild cognitive impairment: a population-based study.

The authors investigated whether engaging in cognitive activities is associated with aging and mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, MN. A random sample of 1,321 study participants ages 70 to 89 (N=1,124 cognitively normal persons, and N=197 subjects with MCI) were interviewed about the frequency of cognitive activities carried out in late life (within 1 year of the date of interview). Computer activities; craft activities, such as knitting, quilting, etc.

Successful aging: definitions and prediction of longevity and conversion to mild cognitive impairment.

Objectives: To examine alternative models of defining and characterizing successful aging.

Design: A retrospective cohort study.

Setting: Olmsted County, MN.

What is the quality of life in the oldest old?

Background: Maintaining and improving quality of life has become a major focus in geriatric medicine, but the oldest old have received limited attention in clinical investigations. We aimed to investigate the relationship between self-perceived and caregiver-perceived quality of life (QOL), cognitive functioning, and depressive symptoms in the oldest old.

Methods: This IRB-approved prospective study recruited community dwellers aged 90-99 years old.

Predicting functional decline in behavioural variant frontotemporal dementia.

Behavioural variant frontotemporal dementia is characterized by a change in comportment. It is associated with considerable functional decline over the course of the illness albeit with sometimes dramatic variability among patients. It is unknown whether any baseline features, or combination of features, could predict rate of functional decline in behavioural variant frontotemporal dementia.

Association of common KIBRA variants with episodic memory and AD risk.

KIBRA single nucleotide polymorphism (SNP) rs17070145 was identified in a genome-wide association study (GWAS) of memory performance, with some but not all follow-up studies confirming association of its T allele with enhanced memory. This allele was associated with reduced Alzheimer's disease (AD) risk in 1 study, which also found overexpression of KIBRA in memory-related brain regions of AD. We genotyped rs17070145 and 14 additional SNPs in 2571 late onset Alzheimer's disease (LOAD) patients vs.

Utility of the DRS for predicting problems in day-to-day functioning.

Predicting the consequences of cognitive impairment relative to day-to-day functioning is challenging, especially when impairment is mild. This study examined the ability of the Dementia Rating Scale (DRS) to predict Record of Independent Living (ROIL) performances in 2469 individuals with varying levels of cognitive ability, and describes specific activities of daily life that are likely impacted given specific DRS scores. Lower DRS scores were associated with greater difficulty in activities of daily living (ADLs), and effects of age, education, and gender were negligible.