Early Clinical Utility Data of a Blood Biomarker Test in the Evaluation of Mild Cognitive Impairment

Abstract There is an important unmet need for timely, noninvasive, low-burden evaluation of patients presenting with mild cognitive impairment (MCI). The PrecivityAD™ blood test quantifies plasma concentrations of amyloid-β 42 and 40 and apolipoprotein E-specific peptides that are combined with age in an algorithm to identify the likelihood of amyloid plaques in the brain as measured by amyloid PET scans. This test has previously demonstrated 92% sensitivity and 77% specificity. The study objective was to evaluate the clinical utility of the test and the Amyloid Probability Score (APS), the test output value. Eighteen patients (median age 72, 55% male, 88% white) with MCI received the PrecivityAD blood-based biomarker test. The mean APS was 31 (range 0-91): 13 patients had low scores (APS 0-35), 2 had high scores (58-100) and 3 had intermediate (inconclusive) scores (APS 36-57). The mean probability of Alzheimer’s disease (AD) diagnosis was rated by clinicians as 63% (range 25-80) pre-test and 31% post-test (range 5-95) (p < 0.0005). AD probability rated by clinicians was decreased in 12/13 low APS patients and increased in 2/2 high APS patients. Donepezil was discontinued in 5/8 low APS patients on therapy and initiated in 1/1 high APS patients not on therapy, representing a change in treatment management in 33% (6/18) of study patients. In summary, this blood-based biomarker test showed clinical utility in its association with physician decision-making around diagnostic certainty and drug therapy management in MCI patients.

Download Full-text

[P2-031]: CLINICAL UTILITY OF AMYLOID PET IN AMNESTIC MILD COGNITIVE IMPAIRMENT

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.06.679 ◽

2017 ◽

Vol 13 (7S_Part_12) ◽

pp. P616-P616

Author(s):

Ko Woon Kim ◽

Sang Won Seo

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Clinical Utility ◽

Amnestic Mild Cognitive Impairment ◽

Amyloid Pet

Download Full-text

Amyloid-β Deposition and Long-Term Progression in Mild Cognitive Impairment due to Alzheimer’s Disease Defined with Amyloid PET Imaging

Journal of Alzheimer s Disease ◽

10.3233/jad-161074 ◽

2017 ◽

Vol 57 (3) ◽

pp. 765-773 ◽

Cited By ~ 10

Author(s):

Shizuo Hatashita ◽

Daichi Wakebe

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Pet Imaging ◽

Amyloid Β ◽

Amyloid Pet ◽

Amyloid Pet Imaging

Download Full-text

Dietary interventions in mild cognitive impairment and dementia

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2019.21.1/niscarmeas ◽

2019 ◽

Vol 21 (1) ◽

pp. 69-82 ◽

Cited By ~ 3

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Functional Outcomes ◽

Clinical Utility ◽

Randomized Clinical Trials ◽

Dietary Intervention ◽

Nutritional Supplements ◽

Dietary Interventions ◽

Dietary Counseling ◽

Nutritional Elements

Dietary intervention is an enticing approach in the fight against cognitive impairment. Nutritional supplements and dietetic counseling are relatively easy and benign interventions, but research has not yet yielded irrefutable evidence as to their clinical utility. Heterogeneity in the results of available clinical studies, as well as methodological and practical issues, does not allow replication and generalization of findings. The paper at hand reviews only randomized clinical trials of single nutrients, multi-nutrient formulations and dietary counseling in mild cognitive impairment and dementia of the Alzheimer's type focusing on both cognitive and functional outcomes. Thus far, folate, vitamin E, Ω-3 fatty acids, and certain multi-nutrient formulations have shown some preliminary promising results; larger, well-designed trials are needed to confirm these findings before nutritional elements can be incorporated in recommended clinical guidelines.

Download Full-text

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

Current Alzheimer Research ◽

10.2174/1567205017666201130094259 ◽

2020 ◽

Vol 17 ◽

Author(s):

Hyung-Ji Kim ◽

Jae-Hong Lee ◽

E-nae Cheong ◽

Sung-Eun Chung ◽

Sungyang Jo ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amnestic Mild Cognitive Impairment ◽

Amyloid Pet ◽

Clinical Progression ◽

Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

Download Full-text

Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-200997 ◽

2021 ◽

pp. 1-13

Author(s):

Dong Bai ◽

Junting Fan ◽

Mengyue Li ◽

Cuixia Dong ◽

Yiming Gao ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Digit Span ◽

Controlled Trial ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Double Blind ◽

Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p < 0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

Download Full-text

Physical Activity and Amyloid-β Brain Levels in Elderly Adults with Intact Cognition and Mild Cognitive Impairment

Journal of the American Geriatrics Society ◽

10.1111/jgs.13530 ◽

2015 ◽

Vol 63 (8) ◽

pp. 1634-1639 ◽

Cited By ~ 23

Author(s):

Philipe de Souto Barreto ◽

Sandrine Andrieu ◽

Pierre Payoux ◽

Laurent Demougeot ◽

Yves Rolland ◽

...

Keyword(s):

Physical Activity ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amyloid Β ◽

Elderly Adults ◽

Brain Levels

Download Full-text

Lipidomic Network of Mild Cognitive Impairment from the Mayo Clinic Study of Aging

Journal of Alzheimer s Disease ◽

10.3233/jad-201347 ◽

2021 ◽

pp. 1-11

Author(s):

Xuewei Wang ◽

Hai Bui ◽

Prashanthi Vemuri ◽

Jonathan Graff-Radford ◽

Clifford R. Jack Jr ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Network Analysis ◽

Mayo Clinic ◽

Plasma Lipids ◽

Amyloid Β ◽

Cognitive Status ◽

Correlation Network ◽

Lipid Species ◽

Clinic Study

Background: Lipid alterations contribute to Alzheimer’s disease (AD) pathogenesis. Lipidomics studies could help systematically characterize such alterations and identify potential biomarkers. Objective: To identify lipids associated with mild cognitive impairment and amyloid-β deposition, and to examine lipid correlation patterns within phenotype groups Methods: Eighty plasma lipids were measured using mass spectrometry for 1,255 non-demented participants enrolled in the Mayo Clinic Study of Aging. Individual lipids associated with mild cognitive impairment (MCI) were first identified. Correlation network analysis was then performed to identify lipid species with stable correlations across conditions. Finally, differential correlation network analysis was used to determine lipids with altered correlations between phenotype groups, specifically cognitively unimpaired versus MCI, and with elevated brain amyloid versus without. Results: Seven lipids were associated with MCI after adjustment for age, sex, and APOE4. Lipid correlation network analysis revealed that lipids from a few species correlated well with each other, demonstrated by subnetworks of these lipids. 177 lipid pairs differently correlated between cognitively unimpaired and MCI patients, whereas 337 pairs of lipids exhibited altered correlation between patients with and without elevated brain amyloid. In particular, 51 lipid pairs showed correlation alterations by both cognitive status and brain amyloid. Interestingly, the lipids central to the network of these 51 lipid pairs were not significantly associated with either MCI or amyloid, suggesting network-based approaches could provide biological insights complementary to traditional association analyses. Conclusion: Our attempt to characterize the alterations of lipids at network-level provides additional insights beyond individual lipids, as shown by differential correlations in our study.

Download Full-text

Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer’s Disease and Other Dementias

Journal of Alzheimer s Disease ◽

10.3233/jad-200890 ◽

2020 ◽

pp. 1-14

Author(s):

Yi-Wen Bao ◽

Anson C.M. Chau ◽

Patrick Ka-Chun Chiu ◽

Yat Fung Shea ◽

Joseph S.K. Kwan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amyloid Β ◽

Standardized Uptake Value ◽

Subjective Cognitive Decline ◽

Cognitively Impaired ◽

Memory Clinic ◽

Pet Ct

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

Download Full-text

Reliability and validity of a Mediterranean diet and culinary index (MediCul) tool in an older population with mild cognitive impairment

British Journal Of Nutrition ◽

10.1017/s0007114518002428 ◽

2018 ◽

Vol 120 (10) ◽

pp. 1189-1200 ◽

Cited By ~ 4

Author(s):

Sue Radd-Vagenas ◽

Maria A. Fiatarone Singh ◽

Michael Inskip ◽

Yorgi Mavros ◽

Nicola Gates ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Mediterranean Diet ◽

Reliability And Validity ◽

Community Dwelling ◽

Systematic Bias ◽

Older Individuals ◽

Retest Reliability ◽

The Mean ◽

Test Retest Reliability

AbstractDementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=−2·30+0·17x) (95 % CI −0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.

Download Full-text