Natural history of mild cognitive impairment in older persons

Bennett, David A.; Wilson, Robert S.; Schneider, Julie A.; Evans, Denis A.; Beckett, Laurel A.; Aggarwal, Neelum T.; Barnes, Lisa L.; Fox, Jacob H.; Bach, Julie

doi:10.1212/wnl.59.2.198

Cited by 882 publications

(903 citation statements)

References 42 publications

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“…In addition to being highly prevalent in MCI/CIND, several studies have linked NPS in CIND/MCI to dementia conversion 7, 13-15 . Modrego et al 16 reported that major depression doubled the risk of transition from MCI to dementia, while a report from the Kungsholmen project suggested a doubling of transition risk with increasing levels of anxiety 17 .…”

Section: Objectivementioning

confidence: 99%

Neuropsychiatric Symptoms as Risk Factors for Progression From CIND to Dementia: The Cache County Study

Peters¹,

Rosenberg²,

Steinberg³

et al. 2013

The American Journal of Geriatric Psychiatry

121

100

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Objectives To examine the association of neuropsychiatric symptom (NPS) severity with risk of transition to all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Design Survival analysis of time to dementia, AD, or VaD onset. Setting Population-based study. Participants 230 participants diagnosed with cognitive impairment, no dementia (CIND) from the Cache County Study of Memory Health and Aging were followed for a mean of 3.3 years. Measurements The Neuropsychiatric Inventory (NPI) was used to quantify the presence, frequency, and severity of NPS. Chi-square statistics, t-tests, and Cox proportional hazard ratios were used to assess associations. Results The conversion rate from CIND to all-cause dementia was 12% per year, with risk factors including an APOE ε4 allele, lower MMSE, lower 3MS, and higher CDR sum-of-boxes. The presence of at least one NPS was a risk factor for all-cause dementia, as was the presence of NPS with mild severity. Nighttime behaviors were a risk factor for all-cause dementia and of AD, while hallucinations were a risk factor for VaD. Conclusions These data confirm that NPS are risk factors for conversion from CIND to dementia. Of special interest is that even NPS of mild severity are a risk for all-cause dementia or AD.

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Section: Objectivementioning

confidence: 99%

Neuropsychiatric Symptoms as Risk Factors for Progression From CIND to Dementia: The Cache County Study

Peters¹,

Rosenberg²,

Steinberg³

et al. 2013

The American Journal of Geriatric Psychiatry

121

100

View full text Add to dashboard Cite

show abstract

“…Indeed, both reference memory (memory for information that is held constant over time) and working memory (the ability to remember, usually for a relatively brief period of time, information that must be distinguished from previously learned similar information) are adversely affected during the aging process [17,[25][26][27]29,32,34,36]. Importantly, such impairments in medial temporal lobe functioning are not an inevitable consequence of the aging process [5,7,19,45]. At advanced chronological ages, a spectrum of mnemonic abilities exists such that some aged individuals perform on par with young adults whereas others experience deficits ranging from mild to profound.…”

Section: Introductionmentioning

confidence: 99%

Spatial reference and working memory across the lifespan of male Fischer 344 rats

Bizon

LaSarge

Montgomery

et al. 2009

Neurobiology of Aging

130

181

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Loss of mnemonic function is among the earliest and most disconcerting consequences of the aging process. This study was designed to provide a comprehensive profile of spatial mnemonic abilities in male Fischer 344 (F344) rats across the lifespan. Young, middle-aged, and aged F344 rats were trained in spatial reference and working memory versions of the water maze task. There was a progressive age-related decline in spatial reference memory across the lifespan. Reliable individual differences were observed among aged rats, with some aged rats performing as well as young cohorts and other performing outside this range. An age-related delay-dependent decline was observed on a working memory version of the water maze task although no relationship between performance on reference and working memory tasks was present. Notably, middle-aged rats were impaired relative to young on both tasks. Together these data demonstrate that individual differences in spatial reference memory exist among aged F344 rats and provide novel data demonstrating an unrelated decline in working memory across the lifespan, suggesting that age-related mnemonic dysfunction may occur across multiple brain systems.

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“…These cases were obtained from the Religious Orders Study, an ongoing longitudinal clinicopathological study of aging and dementia in Catholic nuns, priests, and brothers. 6,138,197,198 Results indicate that tau transcript expression and other cytoskeletal elements (including neurofilament subunits and tubulin, among others) levels did not differ significantly across groups. However, when the ratios of 3Rtau/4Rtau were calculated, a significant difference in the proportion of 3Rtau/4Rtau mRNA was found in MCI and AD relative to NCI.…”

Section: Single Cell Analysis Of Cbf Neurons In Admentioning

confidence: 93%

Single cell gene expression profiling in Alzheimer’s disease

et al. 2006

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Summary: Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

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Natural history of mild cognitive impairment in older persons

Abstract: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.

Cited by 882 publications

References 42 publications

Neuropsychiatric Symptoms as Risk Factors for Progression From CIND to Dementia: The Cache County Study

Neuropsychiatric Symptoms as Risk Factors for Progression From CIND to Dementia: The Cache County Study

Spatial reference and working memory across the lifespan of male Fischer 344 rats

Single cell gene expression profiling in Alzheimer’s disease

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