Undetected Neurodegenerative Disease Biases Estimates of Cognitive Change in Older Adults

Neurodegenerative disease is highly prevalent among older adults and, if undetected, may obscure estimates of cognitive change among aging samples. Our aim in this study was to determine the nature and magnitude of cognitive change in the absence of common neuropathologic markers of neurodegenerative disease. Cognitively normal older adults (ages 65–89 years, N = 199) were classified as normal or abnormal using neuroimaging and cerebrospinal-fluid biomarkers of β-amyloid, tau, and neurodegeneration. When cognitive change was modeled without accounting for biomarker status, significant decline was evident for semantic memory, processing speed, and working memory. However, after adjusting for biomarker status, we found that the rate of change was attenuated and that the biomarker-normal group demonstrated no decline for any cognitive domain. These results indicate that estimates of cognitive change in otherwise healthy older adults will be biased toward decline when the presence of early neurodegenerative disease is not accounted for.

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β-Amyloid is Associated with Reduced Cognitive Function in Healthy Older Adults

Journal of Neuropsychiatry ◽

10.1176/jnp.2008.20.3.327 ◽

2008 ◽

Vol 20 (3) ◽

pp. 327-330 ◽

Cited By ~ 8

Author(s):

John Gunstad ◽

Mary Beth Spitznagel ◽

Ellen Glickman ◽

Thomas Alexander ◽

Judi Juvancic-Heltzel ◽

...

Keyword(s):

Older Adults ◽

Cognitive Function ◽

Healthy Older Adults ◽

Β Amyloid

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0293 Effects of Obstructive Sleep Apnea on Human Spatial Navigational Memory Processing in Cognitively Normal Older Adults

SLEEP ◽

10.1093/sleep/zsz067.292 ◽

2019 ◽

Vol 42 (Supplement_1) ◽

pp. A120-A120

Author(s):

Anna E Mullins ◽

Masrai K Williams ◽

Korey Kam ◽

Ankit Parekh ◽

Bresne Castillo ◽

...

Keyword(s):

Older Adults ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Cognitively Normal ◽

Memory Processing ◽

Obstructive Sleep ◽

Navigational Memory

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The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults

Alzheimer s Research & Therapy ◽

10.1186/s13195-019-0573-1 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Chemin Lin ◽

Maria Ly ◽

Helmet T. Karim ◽

Wenjing Wei ◽

Beth E. Snitz ◽

...

Keyword(s):

Neural Networks ◽

Older Adults ◽

Cognitive Function ◽

Functional Connectivity ◽

Resting State ◽

Clinical Symptoms ◽

Rate Of Change ◽

Resting State Functional Connectivity ◽

Cognitive Changes ◽

Cognitively Normal

Abstract Background Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. Methods We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. Results Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. Conclusions Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.

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Associations of vitamin B12 status with cognitive domain performance in cognitively healthy older adults

Alzheimer s & Dementia ◽

10.1002/alz.043484 ◽

2020 ◽

Vol 16 (S10) ◽

Author(s):

Celeste A de Jager ◽

Liam Nalder ◽

Bang Zheng ◽

Giulia Chiandet ◽

Lefkos T Middleton

Keyword(s):

Older Adults ◽

Vitamin B12 ◽

Cognitive Domain ◽

Healthy Older Adults ◽

Domain Performance

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Correlation of Longitudinal Cerebrospinal Fluid Biomarkers With Cognitive Decline in Healthy Older Adults

Archives of Neurology ◽

10.1001/archneurol.2009.316 ◽

2010 ◽

Vol 67 (2) ◽

Cited By ~ 51

Author(s):

Erik Stomrud ◽

Oskar Hansson ◽

Henrik Zetterberg ◽

Kaj Blennow ◽

Lennart Minthon ◽

...

Keyword(s):

Older Adults ◽

Cerebrospinal Fluid ◽

Cognitive Decline ◽

Healthy Older Adults ◽

Cerebrospinal Fluid Biomarkers

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β-AMYLOID BURDEN PREDICTS LOWER EXTREMITY PERFORMANCE DECLINE IN COGNITIVELY NORMAL OLDER ADULTS

The Gerontologist ◽

10.1093/geront/gnw162.861 ◽

2016 ◽

Vol 56 (Suppl_3) ◽

pp. 218-218

Keyword(s):

Older Adults ◽

Lower Extremity ◽

Amyloid Burden ◽

Cognitively Normal ◽

Lower Extremity Performance ◽

Performance Decline ◽

Β Amyloid

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Apathy and risk of probable incident dementia among community-dwelling older adults

Neurology ◽

10.1212/wnl.0000000000010951 ◽

2020 ◽

Vol 95 (24) ◽

pp. e3280-e3287 ◽

Cited By ~ 1

Author(s):

Meredith A. Bock ◽

Amber Bahorik ◽

Willa D. Brenowitz ◽

Kristine Yaffe

Keyword(s):

Older Adults ◽

Proportional Hazards Model ◽

Cognitive Change ◽

Community Dwelling ◽

Rate Of Change ◽

Cox Proportional Hazards Model ◽

Digit Symbol Substitution Test ◽

Incident Dementia ◽

Increased Risk ◽

Community Dwelling Older Adults

ObjectiveTo evaluate the association between baseline apathy and probable incident dementia in a population-based sample of community-dwelling older adults.MethodsWe studied 2,018 white and black community-dwelling older adults from the Health, Aging, and Body Composition (Health ABC) study. We measured apathy at year 6 (our study baseline) with the modified Apathy Evaluation Scale and divided participants into tertiles based on low, moderate, or severe apathy symptoms. Incident dementia was ascertained over 9 years by dementia medication use, hospital records, or clinically relevant cognitive decline on global cognition. We examined the association between apathy and probable incident dementia using a Cox proportional hazards model adjusting for demographics, cardiovascular risk factors, APOE4 status, and depressed mood. We also evaluated the association between the apathy group and cognitive change (as measured by the modified Mini-Mental State Examination and Digit Symbol Substitution Test over 5 years) using linear mixed effects models.ResultsOver 9 years of follow-up, 381 participants developed probable dementia. Severe apathy was associated with an increased risk of dementia compared to low apathy (25% vs 14%) in unadjusted (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.5–2.5) and adjusted models (HR 1.7, 95% CI 1.3–2.2). Greater apathy was associated with worse cognitive score at baseline, but not rate of change over time.ConclusionIn a diverse cohort of community-dwelling adults, apathy was associated with increased risk of developing probable dementia. This study provides novel evidence for apathy as a prodrome of dementia.

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Prevalence estimates of mild behavioral impairment in a population-based sample of pre-dementia states and cognitively healthy older adults

International Psychogeriatrics ◽

10.1017/s1041610217001909 ◽

2017 ◽

Vol 30 (2) ◽

pp. 221-232 ◽

Cited By ~ 24

Author(s):

Moyra E. Mortby ◽

Zahinoor Ismail ◽

Kaarin J. Anstey

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Diagnostic Criteria ◽

Population Based ◽

Behavioral Impairment ◽

Cognitively Normal ◽

Healthy Older Adults ◽

High Prevalence ◽

Prevalence Estimates ◽

Age Range

ABSTRACTBackground:A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI.Methods:MBI was assessed in 1,377 older (age range 72–79 years; 52% male; MCI ;= 133; cognitively normal, but-at-risk = 397; cognitively healthy = 847). MBI was assessed in accordance with the ISTAART-AA diagnostic criteria for MBI using the neuropsychiatric inventory.Results:34.1% of participants met the criteria for MBI. High prevalence of MBI across the cognitive spectrum was reported (48.9% vs. 43.1% vs. 27.6%). Irrespective of level of cognitive impairment, impulse dyscontrol (33.8% vs. 28.7% vs. 17.2%) and decreased motivation (32.3% vs. 26.2% vs. 16.3%) were the most frequently met MBI domains. MBI was more prevalent in men (χ2 = 4.98, p = 0.026), especially the domains of decreased motivation and impulse dyscontrol.Conclusions:This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

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