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01/2017 journal articles

Original Research

COMPUTERIZED COGNITIVE TESTING FOR USE IN CLINICAL TRIALS: A COMPARISON OF THE NIH TOOLBOX AND COGSTATE C3 BATTERIES

R.F. Buckley, K.P. Sparks, K.V. Papp, M. Dekhtyar, C. Martin, S. Burnham, R.A. Sperling, D.M. Rentz

J Prev Alz Dis 2017;4(1):3-11

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Background: As prevention trials for Alzheimer’s disease move into asymptomatic populations, identifying older individuals who manifest the earliest cognitive signs of Alzheimer’s disease is critical. Computerized cognitive testing has the potential to replace current gold standard paper and pencil measures and may be a more efficient means of assessing cognition. However, more empirical evidence about the comparability of novel computerized batteries to paper and pencil measures is required. Objectives: To determine whether two computerized IPad batteries, the NIH Toolbox Cognition Battery and Cogstate-C3, similarly predict subtle cognitive impairment identified using the Preclinical Alzheimer Cognitive Composite (PACC). Design, Setting, Participants: A pilot sample of 50 clinically normal older adults (Mage=68.5 years±7.6, 45% non-Caucasian) completed the PACC assessment, and the NIH Toolbox and Cogstate-C3 at research centers of Massachusetts General and Brigham and Women’s Hospitals. Participants made 3-4 in-clinic visits, receiving the PACC first, then the NIH Toolbox, and finally the Cogstate-C3. Measurements: Performance on the PACC was dichotomized by typical performance (>= 0.5SD), versus subtle cognitive impairment (<0.5SD). Composites for each computerized battery were created using principle components analysis, and compared with the PACC using non-parametric Spearman correlations. Logistic regression analyses were used to determine which composite was best able to classify subtle cognitive impairment from typical performance. Results: The NIH Toolbox formed one composite and exhibited the strongest within-battery alignment, while the Cogstate-C3 formed two distinct composites (Learning-Memory and Processing Speed-Attention). The NIH Toolbox and C3 Learning-Memory composites exhibited positive correlations with the PACC (ρ=0.49, p<0.001; ρ=0.58, p<0.001, respectively), but not the C3 Processing Speed-Attention composite, ρ=-0.18, p=0.22. The C3 Learning-Memory was the only composite that classified subtle cognitive impairment, and demonstrated the greatest sensitivity (62%) and specificity (81%) for that subtle cognitive impairment. Conclusions: Preliminary findings suggest that the NIH Toolbox has the advantage of showing the strongest overall clustering and alignment with standardized paper-and-pencil tasks. By contrast, Learning-Memory tasks within the Cogstate-C3 battery have the greatest potential to identify cross-sectional, subtle cognitive impairment as defined by the PACC.

CITATION:
R.F. Buckley ; K.P. Sparks ; K.V. Papp ; M. Dekhtyar ; C. Martin ; S. Burnham ; R.A. Sperling ; D.M. Rentz (2017): Computerized Cognitive Testing for Use in Clinical Trials: A Comparison of the NIH Toolbox and Cogstate C3 Batteries. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2017.1

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SHORT-TERM IMPACT OF A COMBINED NUTRACEUTICAL ON COGNITIVE FUNCTION, PERCEIVED STRESS AND DEPRESSION IN YOUNG ELDERLY WITH COGNITIVE IMPAIRMENT: A PILOT, DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

A.F. Cicero, M. Bove, A. Colletti, M. Rizzo, F. Fogacci, M. Giovannini, C. Borghi

J Prev Alz Dis 2017;4(1):12-15

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Background: The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn’t often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders. Objective: To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects. Design: Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice Participants: 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline. Intervention: Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo. Measurements: Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS). Results: MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores. Conclusions: We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

CITATION:
A.F. Cicero ; M. Bove ; A. Colletti ; M. Rizzo ; F. Fogacci ; M. Giovannini ; C. Borghi (2016): Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.110

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GINKGO BILOBA EXTRACT CONSUMPTION AND LONG-TERM OCCURRENCE OF DEATH AND DEMENTIA

J.F. Dartigues, L. Grasset, C. Helmer, C. Féart, L. Letenneur, H. Jacqmin-Gadda, P. Joly, H. Amieva

J Prev Alz Dis 2017;4(1):16-20

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Objectives: To study the benefit of Ginkgo Biloba Extract (GBe) consumption on the long term risk of dementia and death in elderly people. Design: The Paquid study is a population-based cohort with regular follow-up screenings up to twenty-two years and systematic detection of incident cases of dementia. Statistical analysis was conducted with an illness-death model dealing with interval censoring of dementia and competing risk of death. Setting: The sample was randomly selected from electoral rolls in two administrative areas of southwestern France in 1988-1989. Participants: 3,777 subjects aged 65 years or older at baseline who were living at home Measurement: Participants were visited at home by a trained psychologist at baseline in 1988/1989, and then again approximately every two years. Drug consumption for the treatment of cognitive or neurosensory impairment was collected at baseline. Participants were classified as GBe consumers, other drug (OD) consumers and untreated controls (UC) for this motive. Results: After adjustment for sociodemographic factors and cognitive measures at baseline the risk for dementia was not significantly different in GBe consumers and UC (Hazard Ratio (HR)=1.21, 95% Confidence Interval (95% CI)=0.95-1.55, p=0.42) and it was of the same magnitude but significantly increased in the OD group versus UC (HR=1.25, 95% CI=1.06-1.46, p=0.004). With the same adjustment, the risk of dying in non-demented subjects was reduced in GBe consumers versus UC (HR=0.67, 95% CI=0.49-0.93, p=0.02) while it was the same as the reference group in OD consumers. The mean lifetimes without dementia was of 11.2 years in the UC group (95% CI=10.9-11.5), 11.1 years in the GBe group (10.2-11.9) and 9.1 years for the OD group (8.7-9.6). Conclusion: GBe consumers have a lower risk of dying before dementia and a longer lifetime without dementia than participants taking other drugs for the same indication.

CITATION:
J.F. Dartigues ; L. Grasset ; C. Helmer ; C. Féart ; L. Letenneur ; H. Jacqmin-Gadda ; P. Joly ; H. Amieva (2016): Ginkgo Biloba Extract Consumption and Long-term Occurrence of Death and Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.105

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STIMULUS-LOCKED LATERALIZED READINESS POTENTIAL AND PERFORMANCE: USEFUL MARKERS FOR DIFFERENTIATING BETWEEN AMNESTIC SUBTYPES OF MILD COGNITIVE IMPAIRMENT

S. Cid-Fernández, M. Lindín, F. Díaz

J Prev Alz Dis 2017;4(1):21-28

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BACKGROUND: The findings of previous studies, in which event-related potentials (ERPs) related to stimulus evaluation were measured, do not fully explain the behavioral decline observed in amnestic mild cognitive impairment (aMCI; prodromal stage of Alzheimer’s Disease). OBJECTIVES: Motor ERPs were evaluated in this study with the aim of discovering complementary explanations and identifying aMCI biomarkers. DESIGN: Cross-sectional study. SETTING: Santiago de Compostela, Galicia, Spain. PARTICIPANTS: Nineteen healthy control (52-81 years old), 21 single-domain aMCI (sdaMCI; 51-87 years old) and 12 multi-domain aMCI (mdaMCI, 62-85 years old) adults. MEASUREMENTS: Reaction times (RTs), percentage of hits, and stimulus-locked and response-locked lateralized readiness potentials (sLRP and rLRP, indexes of response selection and preparation) were evaluated. RESULTS: mdaMCI participants showed longer RTs than control adults and less hits than control and sdaMCI participants. In addition, the mdaMCI group showed lower sLRP amplitudes than the control participants, and the sdaMCI group showed longer sLRP peak latencies. CONCLUSIONS: Control and sdaMCI groups did not differ in relation to RTs or hits, although sLRP peak latencies (sensitivity and specificity >.73) were longer in the sdaMCI group, which may be a sign of compensatory mechanisms or early indication of a decline in motor control. RTs were longer and sLRP amplitudes were smaller in the mdaMCI than in the Control group, and mdaMCI scored fewer hits than control and sdaMCI participants, indicating behavioral and neurocognitive deficits. The combination of hits and RTs discriminated mdaMCI from control adults (sensitivity and specificity >.82); and the combination of sLRP peak latency and hits discriminated mdaMCI from sdaMCI adults (sensitivity=1.00, specificity=.88).

CITATION:
S. Cid-Fernández ; M. Lindín ; F. Díaz (2016): Stimulus-Locked Lateralized Readiness Potential and Performance: Useful Markers for Differentiating between Amnestic Subtypes of Mild Cognitive Impairment. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.88

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ASSESSING THE RELATIONSHIP BETWEEN VITAMIN D STATUS AND IMPAIRMENTS IN COGNITIVE AND PHYSICAL PERFORMANCE IN OLDER ADULTS USING A DUAL TASK PHYSICAL PERFORMANCE TEST

J. Lopez, A. Campa, J.E. Lewis, F.G. Huffman, J.P. Liuzzi, T. Li, A.H. Martinez, S.M. Ferris, A. Rasul, A. Farooqi, A.M. Lopez Medrano, S.E. Atlas, E. Tiozzo, J. Konefal, J.M. Woolger

J Prev Alz Dis 2017;4(1):29-36

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Background: Vitamin D deficiency has been associated with an increased risk of falls in older adults. Several studies have demonstrated an association between vitamin D deficiency and gait and cognitive impairments, which are two risk factors for falls in the elderly. There is lack of research about the role of vitamin D in cognitive function in the context of mobility. Objective: The purpose of this study was to evaluate the association between vitamin D status with the age-related changes in mobility through higher order cognitive function using a dual task physical performance test. Design: Cross-sectional Setting: Community-dwelling older adult population located in Miami, Fl. Participants: Healthy participants over the age of 55 (n=97) who participated in the parent interventional study. Measurements: Participants completed assessments that included serum levels of vitamin D, surveys, and dual task physical performance tests. Spearman’s correlations, independent t-tests, repeated measures ANOVAs and multiple logistic regressions were used to examine the relationship between vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml) and sufficiency (≥30 ng/ml) and dual task physical performance variables. The significance level was set at α=0.05. Results: There were no significant associations between vitamin D insufficiency and gait velocity during either task. Using Spearman correlations, slower single (P=0.011) and dual task counting rates (P=0.006) were significantly associated with vitamin D insufficiency. Independent t-tests showed dual and single task counting rates were significantly lower in the vitamin D insufficient group compared to the sufficient group (P=0.018 and P=0.028, respectively). The results for the ANOVAs indicated that velocities and counting rates were not significantly different by vitamin D status (Wilk’s Lambda =0.999; F (1, 95) =.11, P=.740) (Wilk’s Lambda =.999, F(1,95)=.13, P=.718). Vitamin D status was not significantly associated with dual task physical performance (defined as the difference in dual and single task) in gait velocity (OR=1.00, 95% CI: 0.98; 1.02, P=0.772) and counting rate (OR=1.684, 95% CI: 0.15; 19.57, P=0.677), when controlling for confounders. Conclusions: Since counting backward is a mental tracking task, which is a component of executive function, our results suggest a relationship between vitamin D insufficiency and executive dysfunction. Executive dysfunction has been previously associated with fall risks in the elderly, and it could be a possible mediator between vitamin D and falls. Our data suggest that cognition may play a significant role in vitamin D’s influence on falls, while motor function may play a lesser role.

CITATION:
J. Lopez ; A. Campa ; J.E. Lewis ; F.G. Huffman ; J.P. Liuzzi ; T. Li ; A.H. Martinez ; S.M. Ferris ; A. Rasul ; A. Farooqi ; A.M. Lopez Medrano ; S.E. Atlas ; E. Tiozzo ; J. Konefal ; J.M. Woolger (2016): Assessing the Relationship between Vitamin D Status and Impairments in Cognitive and Physical Performance in Older Adults Using a Dual Task Physical Performance Test . The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.114

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MODEST OVERWEIGHT AND HEALTHY DIETARY HABITS REDUCE RISK OF DEMENTIA: A NATIONWIDE SURVEY IN TAIWAN

C.-Y. Lee, Y. Sun, H.-J. Lee, T.-F. Chen, P.-N. Wang, K.-N. Lin, L.-Y. Tang, C.-C.Lin, M.-J. Chiu

J Prev Alz Dis 2017;4(1):37-43

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Background: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. Objective: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. Design: Cross-sectional observational study. Setting: A nationwide, population-based, door-to-door, in-person survey. Participants: Selected by computerized random sampling from all 19 counties in Taiwan. Measurement: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer’s Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. Results: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). Conclusions: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.

CITATION:
C.-Y. Lee ; Y. Sun ; H.-J. Lee ; T.-F. Chen ; P.-N. Wang ; K.-N. Lin ; L.-Y. Tang ; C.-C.Lin ; M.-J. Chiu (2016): Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.123

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COGNITIVE PERFORMANCE DOES NOT LIMIT PHYSICAL ACTIVITY PARTICIPATION IN THE LIFESTYLE INTERVENTIONS AND INDEPENDENCE FOR ELDERS PILOT STUDY (LIFE-P)

K.F. Reid, M.P. Walkup, J.A. Katula, K.M. Sink, S. Anton, R. Axtell, D.R. Kerwin, A.C. King, A.F. Kramer, M.E. Miller, V. Myers, C. Rosano, S.A. Studenski, O.L. Lopez, J. Verghese, R.A. Fielding, J. Williamson

J Prev Alz Dis 2017;4(1):44-50

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Objectives: We examined whether multiple domains of baseline cognitive performance were associated with prospective physical activity (PA) adherence in the Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P). Design, Setting, Participants: The LIFE-P study was a single-blind, multicenter, randomized controlled trial of a PA intervention compared to a successful aging educational intervention in sedentary, mobility-limited older adults. Intervention: A 12-month structured, moderate-intensity, multi-modal PA program that included walking, resistance training, and flexibility exercises. For the first 2 months (adoption), 3 center-based exercise sessions (40–60 min) / week were conducted. During the next 4 months (transition), center-based sessions were conducted 2 times / week. The subsequent maintenance phase consisted of optional once-to-twice-per-week center-based sessions and home-based PA. Measurements: Tests of executive and global cognitive functioning, working memory and psychomotor speed were administered at baseline. Median test scores were used to dichotomize participants into low or high cognitive performance groups. Results: 52 mobility-limited older adults (age: 76.9 ±5 yrs) were randomized to the PA arm of LIFE-P. Compared to participants with high cognitive performance, participants with low performance had similar PA adherence rates (all P ≥ 0.34). Furthermore, weak and non-significant univariate relationships were elicited between all measures of cognition and overall PA adherence levels (r values ranged: -0.20 to 0.12, P ≥ 0.12). Conclusion: These data suggest that cognitive performance does not limit long-term PA adherence in mobility-limited older adults. Additional studies in larger cohorts are warranted to verify these findings.

CITATION:
K.F. Reid ; M.P. Walkup ; J.A. Katula ; K.M. Sink ; S. Anton ; R. Axtell ; D.R. Kerwin ; A.C. King ; A.F. Kramer ; M.E. Miller ; V. Myers ; C. Rosano ; S.A. Studenski ; O.L. Lopez ; J. Verghese ; R.A. Fielding ; J. Williamson (2016): Cognitive Performance Does not Limit Physical Activity Participation in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.107

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Review Articles

A KETO-MEDIET APPROACH WITH COCONUT SUBSTITUTION AND EXERCISE MAY DELAY THE ONSET OF ALZHEIMER’S DISEASE AMONG MIDDLE-AGED

B.C. Perng, M. Chen, J.C. Perng, P. Jambazian

J Prev Alz Dis 2017;4(1):51-57

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Background: Coconut oil has been widely used to improve health because there is much information available by word of mouth, in books, and on the internet. However, researchers still continue to search for the best diets to improve the quality of life, especially for people with cognitive decline. Objectives: The aim of this review is to develop a novel dietary approach, the Keto-Mediet, which may help prevent the onset of Alzheimer’s disease. Methods: Evidence gained through literature review from 1982 to 2015 on gene-by-diet interaction and lipid and glucose metabolism in the brains of Alzheimer’s patients is converted into the new Keto-Mediet approach. Design: The Keto-Mediet approach combines the benefits of a Ketogenic diet and a Mediterranean diet into a pyramidal model that is rich in various types of vitamins and substitutes coconuts for saturated animal fats. Limited glucose intake is intended to delay brain degeneration. A revised adult food pyramid was created to illustrate the principles of the Keto-Mediet approach. Conclusion: The Keto-Mediet approach represents and interprets food groups according to the revised adult food pyramid. This approach also encourages adherence to this healthy diet and lifestyle changes including exercise for people whose age ranges from 40 to 75 years. Those who comply with this approach will significantly enhance their knowledge and adopt a healthier lifestyle, as compared to those whose modern eating patterns are typically less healthy. Therefore, the Keto-Mediet approach can be applied in hopes of preventing and decreasing Alzheimer’s disease in different ethnicities and cultural groups.

CITATION:
B.C. Perng ; M. Chen ; J.C. Perng ; P. Jambazian (2016): A Keto-Mediet Approach with Coconut Substitution and Exercise May Delay the Onset of Alzheimer’s Disease among Middle-Aged. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.104

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ANTIOXIDANTS IN THE DIET AND COGNITIVE FUNCTION: WHICH ROLE FOR THE MEDITERRANEAN LIFE-STYLE?

C. Vassalle, L. Sabatino, A. Pingitore, K. Chatzianagnostou, F. Mastorci, R. Ceravolo

J Prev Alz Dis 2017;4(1):58-64

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This review aims to focus on main antioxidants- abundantly contained in the diet- as well as of the whole Mediterranean diet and life-style and their relationship with cognitive function, especially critical in two phases of life, in children until adolescence and oldness. The role of emerging biochemical and molecular biomarkers as opportunity to estimate more accurately nutritional assumption and requirement, in terms of cognitive preservation and disease risk, will be also discussed. The cluster of factors within the Mediterranean pattern -which include not only nutritional, but also physical, social, and stimulating aspects- is still largely understudied as a whole, but it is proposed as attractive research area and tool for public health planning of prevention and intervention.

CITATION:
C. Vassalle ; L. Sabatino ; A. Pingitore ; K. Chatzianagnostou ; F. Mastorci ; R. Ceravolo (2016): Antioxidants in the Diet and Cognitive Function: Which Role for the Mediterranean Life-style?. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2016.109

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