CSF biomarkers of Alzheimer disease

Roe, Catherine M.; Grant, Elizabeth; Holtzman, David M.; Morris, John C.

doi:10.1212/01.wnl.0000436940.78152.05

Cited by 26 publications

(23 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Such a finding corroborates our previous study, which showed that depression scores and other behavioral symptoms monitored by the NPI-Q worsen faster among individuals with preclinical AD dementia at baseline as defined by CSF biomarkers. 13 While depression measured by the NPI-Q is associated with preclinical AD dementia in this study, with the exception of memory, the occurrence of GDS items with time did not differ dramatically between participants who remained at and those who progressed beyond CDR 0. Both groups showed significant decreases in energy and interest in activities alongside an increased preference for staying home on the GDS.…”

contrasting

confidence: 47%

“Noncognitive” symptoms of early Alzheimer disease

Masters¹,

Morris²,

Roe³

2015

Neurology

Self Cite

159

117

View full text Add to dashboard Cite

Objectives: To observe the natural time course of noncognitive symptoms before the onset of symptomatic Alzheimer disease dementia.Methods: Using the National Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March 2013, data from cognitively normal individuals who were aged 50 years or older at first visit and had subsequent follow-up were analyzed. Survival analyses were used to examine the development of particular symptoms relative to each other on the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire, and Geriatric Depression Scale, and to compare the development of individual symptoms for persons who did and did not receive a Clinical Dementia Rating (CDR) .0 (indicating abnormal cognition) during the follow-up period.Results: The order of symptom occurrence on the NPI-Q was similar for participants who remained at CDR 0 and for those who received a CDR .0 over the follow-up period, although the time to most NPI-Q symptoms was faster for participants who received a CDR .0 (p , 0.001). With the exception of memory, Geriatric Depression Scale symptoms reported by both CDR groups were similar. Conclusions:We found a significantly earlier presence of positive symptoms on the NPI-Q in cognitively normal patients who subsequently developed CDR .0. Among participants with no depression symptoms at baseline, results suggest that depressive symptoms may increase with aging regardless of incipient dementia. Such findings begin to delineate the noncognitive course of Alzheimer disease dementia in the preclinical stages. Future research must further elucidate the correlation between noncognitive changes and distinct dementia subtypes. The natural course of Alzheimer disease (AD) dementia includes hallmark functional and behavioral deficits in addition to cognitive decline. Alternately termed behavioral and psychological symptoms in dementia or neuropsychiatric symptoms (NPS), this heterogeneous array of noncognitive impairment affects an estimated 90% of patients with AD.1 Earlier studies have shown that with advancing cognitive decline in AD dementia, noncognitive symptoms include apathy, depression, agitation, and aggression, to psychosis. With progressive cognitive and functional decline in AD dementia, the presence of NPS is postulated to represent increased neurodegradation across neural systems.2-5 Such NPS have been associated with worse prognosis, accelerated illness progression, increased use of services, and earlier institutionalization.2 However, variable neuropsychiatric measures and clinical definitions have clouded the true incidence and progression of NPS in patients with AD.While noncognitive outcomes of AD after incident dementia are increasingly characterized, the relative time course of behavioral and functional deficits before onset of cognitive impairment in AD dementia has been rarely studied. Here, we examined the time course of noncognitive symptoms reported on the Functional Activities Questionnaire (FAQ), 6 Geriatric Depression

show abstract

contrasting

confidence: 47%

“Noncognitive” symptoms of early Alzheimer disease

Masters¹,

Morris²,

Roe³

2015

Neurology

Self Cite

159

117

View full text Add to dashboard Cite

show abstract

“…19 Strikingly, studies looking at decline in cognition over a relatively short time period (a few years) among persons cognitively normal at baseline have indicated that the ratio of CSF tau/Aβ 42 is a better predictor of decline than either Aβ 42 or tau by themselves. 8, 34 Thus, like cognition, variables reflecting combinations of biomarkers may be better predictors of decline in noncognitive outcomes such as mood, compared to individual biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…6–8 However, the current literature on mood in preclinical AD is skewed to the evaluation of singular, negative dimensions of mood (e.g. depression, anxiety).…”

Section: Introductionmentioning

confidence: 99%

Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels

Babulal¹,

Ghoshal²,

Head

et al. 2016

The American Journal of Geriatric Psychiatry

110

View full text Add to dashboard Cite

Objectives To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. Setting Knight Alzheimer’s Disease Research Center (ADRC) at Washington University (WU). Participants Participants, 65 year of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. Measurements CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p >0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < .05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning Conclusion Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults.

show abstract

“…We have previously explored whether CSF Aβ 1–42 , tau, ptau 181 , tau/Aβ 1–42 , and ptau 181 /Aβ 1–42 predict future decline in the same non-cognitive outcomes we explored [22]. They found that abnormal levels of each biomarker were related to greater impairment over time in all non-cognitive outcomes tested.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, participants were a subset of the participants enrolled in the Knight ADRC whose data were used for a 2013 study by Roe et al [22], who had completed CSF and structural neuroimaging studies. The Knight ADRC recruits participants for yearly assessments from the greater St. Louis area through word-of-mouth, advertisements, and community events.…”

Section: Methodsmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

Ingber

Hassenstab²,

Benzinger³

et al. 2016

JAD

View full text Add to dashboard Cite

Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

show abstract

CSF biomarkers of Alzheimer disease

Cited by 26 publications

References 20 publications

“Noncognitive” symptoms of early Alzheimer disease

“Noncognitive” symptoms of early Alzheimer disease

Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

Contact Info

Product

Resources

About