Objective: Determine content and concurrent validity of six multiple choice questions (MCQ) on Al... more Objective: Determine content and concurrent validity of six multiple choice questions (MCQ) on Alzheimer’s disease (AD) prevention and risk reduction by correlating scores with the previously validated Alzheimer’s Disease Knowledge Scale (ADKS). Background: Internet-based educational interventions have potential to broadly impact knowledge, behavioral change, and participation in clinical trials. Alzheimer’s Universe (www.AlzU.org), an online AD educational platform and learning management system has demonstrated significant improvements in patient/caregiver AD knowledge, and increased interest in clinical trial participation, yet valid instruments to assess knowledge of AD prevention and risk reduction do not currently exist. Design/Methods: An evidence-based AD curriculum and online lessons were developed by a multi-disciplinary, expert team. Identical lesson content and length were arranged in both written blog-post and interactive webinar formats. Users were AD caregivers, at ri...
Objective: Assess effectiveness of multi-modal interventions on Alzheimer’s disease (AD), dementi... more Objective: Assess effectiveness of multi-modal interventions on Alzheimer’s disease (AD), dementia, and vascular risk scales. Secondary outcomes include overall and differential effectiveness of interventions on blood biomarkers and cognition (based on genotype and physician/patient reported adherence). Background: The Alzheimer’s Prevention Clinic at Weill Cornell Medicine provides clinical care to patients who undergo comprehensive assessments and receive evidence-based, individualized interventions applying principles of pharmacogenomics, nutrigenomics and clinical precision medicine. Design/Methods: In this prospective cohort study, patients with family history of AD and no or minimal cognitive complaints (primary prevention), and those meeting criteria for preclinical AD or mild cognitive impairment were recruited to our registry. Clinical evaluations were performed at baseline including cognition (NIH Toolbox Cognition Battery, Verbal Fluency, Trails B, MMSE), anthropometrics,...
The Journal of Prevention of Alzheimer's Disease, 2015
In July 2013, Weill Cornell Medical College founded the first Alzheimer’s Prevention Clinic (APC)... more In July 2013, Weill Cornell Medical College founded the first Alzheimer’s Prevention Clinic (APC) in the United States, providing direct clinical care to family members of patients with Alzheimer’s disease (AD) as part of the Weill Cornell Memory Disorders Program. At the APC, patients seeking to lower their AD risk undergo a comprehensive assessment, receive a personalized plan based on rapidly evolving scientific evidence, and are followed over time using validated as well as emerging clinical and research technologies. The APC approach applies the principles of pharmacogenomics, nutrigenomics and clinical precision medicine, to tailor individualized therapies for patients. Longitudinal measures currently assessed in the clinic include anthropometrics, cognition, blood biomarkers (i.e., lipid, inflammatory, metabolic, nutritional) and genetics, as well as validated, self-reported measures that enable patients to track several aspects of health-related quality of life. Patients are...
Background: Prodromal Neurodegenerative Disease (ND) due to tauopathies such as Alzheimer’s Disea... more Background: Prodromal Neurodegenerative Disease (ND) due to tauopathies such as Alzheimer’s Disease (AD) and Synucleinopathies (SN) such as Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB) present subtly. Although ND are considered cognitive disorders, in fact ND present with behavioral and even medical symptomatology years to decades prior to the onset of cognitive changes. Recognizing prodromal ND syndromes is a public health priority because ND is common, disabling and expensive. Diagnosing prodromal ND in real world clinical settings is challenging because ND of the same pathology can present with different symptoms in different people. Individual variability in nature and variability in nurture across the life course influence how ND pathology manifests clinically. The objective of this study was to describe how non-cognitive symptoms from behavioral, medical, neurological and psychiatric domains cluster in prodromal and early stages of ND. Methods: This was an ...
Neurodevelopmental learning and attentional disorders (NLAD) such as dyslexia, dyscalculia and at... more Neurodevelopmental learning and attentional disorders (NLAD) such as dyslexia, dyscalculia and attention deficit hyperactivity disorder (ADHD) affect at least 6% of the adult population or more. They are associated with atypical cognitive patterns in early and adult life. The cognitive patterns of affected individuals in late life have never been described. One main challenge is detecting individuals in clinical settings during which mild cognitive changes could be confounding the clinical presentation. This is a critical research gap because these conditions interact, across the life course, with an individual's risk for dementia. Also, learning disabilities which present in childhood pose persistent cognitive differences in areas involving executive function, reading and math. Clinicians lack tools to detect undiagnosed neurodevelopmental in adults with memory disorders. The majority of patients presenting at memory clinics today come from a generation during which NLAD were n...
Journal of public health (Oxford, England), Jan 9, 2017
Understanding health beliefs and how they influence willingness will enable the development of ta... more Understanding health beliefs and how they influence willingness will enable the development of targeted curricula that maximize public engagement in Alzheimer's disease (AD) risk reduction behaviors. Literature on behavioral theory and community input was used to develop and validate a health beliefs survey about AD risk reduction among 428 community-dwelling adults. Principal component analysis was performed to assess internal consistency. Linear regression was performed to identify key predictors of Willingness to engage in AD risk reduction behaviors. The measure as well as the individual scales (Benefits, Barriers, Severity, Susceptibility and Social Norm) were found to be internally consistent. Overall, as Benefits and Barriers scores increased, Willingness scores also increased. Those without prior AD experience or family history had lower willingness scores. Finally, we observed an interaction between age and norms, suggesting that social factors related to AD prevention ...
OBJECTIVE: Study the clinical and neuropathological correlates of patterns of abnormal tau deposi... more OBJECTIVE: Study the clinical and neuropathological correlates of patterns of abnormal tau deposition within the hippocampus. BACKGROUND: Alzheimer’s Disease (AD) is marked by cerebral deposition of phospho-tau. Patterns of phospho-tau accumulation within the three-layered hippocampus vary. There is increasing interest in lamina-specific tau changes in aging, AD and dementia because they may reflect trans-synaptic propagation of phospho-tau along neuroanatomical pathways. Here, we studied patterns of tau deposition within the inner (IML) and outer (OML) molecular layers of the dentate gyrus. DESIGN/METHODS: This series included 98 consecutive autopsied brains from the Alzheimer’s Disease Research Center, stained for phospho-tau with AT-8. Density of staining was rated as High vs. Low within IML and OML. Inter-rater reliabilities were kappa=0.8 for IML and kappa=0.6 for OML. Subjects were grouped according to four patterns: IML+OML (n=44), OML-only (n=35), IML-only (n=5), and neither (n-14), and compared with respect to neuropathological diagnoses, clinical dementia status (yes/no), Braak neurofibrillary tangle stage, age of symptom onset and age of death. RESULTS: Among all subjects, those with high AT-8 staining in IML+OML, vs. OML-only, were more likely to fulfill CERAD criteria for Definite AD (93% vs. 66%, p<0.01). This group also had higher mean Braak stage (5.8 vs. 4.5, p<0.01), earlier mean age of onset (65.9 vs. 73.7 yrs, p=0.02) and earlier mean age of death (78.1vs. 86.2 yrs, p<0.01). In logistic regression, the association between IML+OML and Definite AD remained significant after adjusting for age of death, gender, ethnicity, education and clinical dementia status (OR 5.7, p=0.04). Analyses restricted to the 70 subjects with Definite AD showed that IML+OML staining (compared to OML-only) was associated with higher Braak stage and earlier age of death. CONCLUSIONS: Phospho-tau deposition in AD occurs within IML and/or OML. Prominent IML involvement is associated with earlier age of death in AD. Support included NIH/NIA grant #P50AG08702 and the Taub Institute. Disclosure: Dr. Seifan has nothing to disclose. Dr. Noble has nothing to disclose. Dr. Mez has nothing to disclose. Dr. Marder has received personal compensation in an editorial capacity for Current Neuroscience. Dr. Marder has received research support from the National Institutes of Health, Michael J Fox Foundation, Parkinson Disease Foundation, CHDI Foundation, and Huntington9s Disease Soceity of America. Dr. Honig has received personal compensation for activities with Johnson & Johnson, Janssen, and the Gerson Lehman Group. Dr. Honig has received personal compensation in an editorial capacity for American Medical Association/Archives of Neurology. Dr. Honig has received research support from Allon, Baxter, Bristol-Myers Squibb Company, Elan Corporation, Genentech, Inc., Eli Lilly & Company, Janssen, and Pfizer Inc.
Objective: Determine content and concurrent validity of six multiple choice questions (MCQ) on Al... more Objective: Determine content and concurrent validity of six multiple choice questions (MCQ) on Alzheimer’s disease (AD) prevention and risk reduction by correlating scores with the previously validated Alzheimer’s Disease Knowledge Scale (ADKS). Background: Internet-based educational interventions have potential to broadly impact knowledge, behavioral change, and participation in clinical trials. Alzheimer’s Universe (www.AlzU.org), an online AD educational platform and learning management system has demonstrated significant improvements in patient/caregiver AD knowledge, and increased interest in clinical trial participation, yet valid instruments to assess knowledge of AD prevention and risk reduction do not currently exist. Design/Methods: An evidence-based AD curriculum and online lessons were developed by a multi-disciplinary, expert team. Identical lesson content and length were arranged in both written blog-post and interactive webinar formats. Users were AD caregivers, at ri...
Objective: Assess effectiveness of multi-modal interventions on Alzheimer’s disease (AD), dementi... more Objective: Assess effectiveness of multi-modal interventions on Alzheimer’s disease (AD), dementia, and vascular risk scales. Secondary outcomes include overall and differential effectiveness of interventions on blood biomarkers and cognition (based on genotype and physician/patient reported adherence). Background: The Alzheimer’s Prevention Clinic at Weill Cornell Medicine provides clinical care to patients who undergo comprehensive assessments and receive evidence-based, individualized interventions applying principles of pharmacogenomics, nutrigenomics and clinical precision medicine. Design/Methods: In this prospective cohort study, patients with family history of AD and no or minimal cognitive complaints (primary prevention), and those meeting criteria for preclinical AD or mild cognitive impairment were recruited to our registry. Clinical evaluations were performed at baseline including cognition (NIH Toolbox Cognition Battery, Verbal Fluency, Trails B, MMSE), anthropometrics,...
The Journal of Prevention of Alzheimer's Disease, 2015
In July 2013, Weill Cornell Medical College founded the first Alzheimer’s Prevention Clinic (APC)... more In July 2013, Weill Cornell Medical College founded the first Alzheimer’s Prevention Clinic (APC) in the United States, providing direct clinical care to family members of patients with Alzheimer’s disease (AD) as part of the Weill Cornell Memory Disorders Program. At the APC, patients seeking to lower their AD risk undergo a comprehensive assessment, receive a personalized plan based on rapidly evolving scientific evidence, and are followed over time using validated as well as emerging clinical and research technologies. The APC approach applies the principles of pharmacogenomics, nutrigenomics and clinical precision medicine, to tailor individualized therapies for patients. Longitudinal measures currently assessed in the clinic include anthropometrics, cognition, blood biomarkers (i.e., lipid, inflammatory, metabolic, nutritional) and genetics, as well as validated, self-reported measures that enable patients to track several aspects of health-related quality of life. Patients are...
Background: Prodromal Neurodegenerative Disease (ND) due to tauopathies such as Alzheimer’s Disea... more Background: Prodromal Neurodegenerative Disease (ND) due to tauopathies such as Alzheimer’s Disease (AD) and Synucleinopathies (SN) such as Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB) present subtly. Although ND are considered cognitive disorders, in fact ND present with behavioral and even medical symptomatology years to decades prior to the onset of cognitive changes. Recognizing prodromal ND syndromes is a public health priority because ND is common, disabling and expensive. Diagnosing prodromal ND in real world clinical settings is challenging because ND of the same pathology can present with different symptoms in different people. Individual variability in nature and variability in nurture across the life course influence how ND pathology manifests clinically. The objective of this study was to describe how non-cognitive symptoms from behavioral, medical, neurological and psychiatric domains cluster in prodromal and early stages of ND. Methods: This was an ...
Neurodevelopmental learning and attentional disorders (NLAD) such as dyslexia, dyscalculia and at... more Neurodevelopmental learning and attentional disorders (NLAD) such as dyslexia, dyscalculia and attention deficit hyperactivity disorder (ADHD) affect at least 6% of the adult population or more. They are associated with atypical cognitive patterns in early and adult life. The cognitive patterns of affected individuals in late life have never been described. One main challenge is detecting individuals in clinical settings during which mild cognitive changes could be confounding the clinical presentation. This is a critical research gap because these conditions interact, across the life course, with an individual's risk for dementia. Also, learning disabilities which present in childhood pose persistent cognitive differences in areas involving executive function, reading and math. Clinicians lack tools to detect undiagnosed neurodevelopmental in adults with memory disorders. The majority of patients presenting at memory clinics today come from a generation during which NLAD were n...
Journal of public health (Oxford, England), Jan 9, 2017
Understanding health beliefs and how they influence willingness will enable the development of ta... more Understanding health beliefs and how they influence willingness will enable the development of targeted curricula that maximize public engagement in Alzheimer's disease (AD) risk reduction behaviors. Literature on behavioral theory and community input was used to develop and validate a health beliefs survey about AD risk reduction among 428 community-dwelling adults. Principal component analysis was performed to assess internal consistency. Linear regression was performed to identify key predictors of Willingness to engage in AD risk reduction behaviors. The measure as well as the individual scales (Benefits, Barriers, Severity, Susceptibility and Social Norm) were found to be internally consistent. Overall, as Benefits and Barriers scores increased, Willingness scores also increased. Those without prior AD experience or family history had lower willingness scores. Finally, we observed an interaction between age and norms, suggesting that social factors related to AD prevention ...
OBJECTIVE: Study the clinical and neuropathological correlates of patterns of abnormal tau deposi... more OBJECTIVE: Study the clinical and neuropathological correlates of patterns of abnormal tau deposition within the hippocampus. BACKGROUND: Alzheimer’s Disease (AD) is marked by cerebral deposition of phospho-tau. Patterns of phospho-tau accumulation within the three-layered hippocampus vary. There is increasing interest in lamina-specific tau changes in aging, AD and dementia because they may reflect trans-synaptic propagation of phospho-tau along neuroanatomical pathways. Here, we studied patterns of tau deposition within the inner (IML) and outer (OML) molecular layers of the dentate gyrus. DESIGN/METHODS: This series included 98 consecutive autopsied brains from the Alzheimer’s Disease Research Center, stained for phospho-tau with AT-8. Density of staining was rated as High vs. Low within IML and OML. Inter-rater reliabilities were kappa=0.8 for IML and kappa=0.6 for OML. Subjects were grouped according to four patterns: IML+OML (n=44), OML-only (n=35), IML-only (n=5), and neither (n-14), and compared with respect to neuropathological diagnoses, clinical dementia status (yes/no), Braak neurofibrillary tangle stage, age of symptom onset and age of death. RESULTS: Among all subjects, those with high AT-8 staining in IML+OML, vs. OML-only, were more likely to fulfill CERAD criteria for Definite AD (93% vs. 66%, p<0.01). This group also had higher mean Braak stage (5.8 vs. 4.5, p<0.01), earlier mean age of onset (65.9 vs. 73.7 yrs, p=0.02) and earlier mean age of death (78.1vs. 86.2 yrs, p<0.01). In logistic regression, the association between IML+OML and Definite AD remained significant after adjusting for age of death, gender, ethnicity, education and clinical dementia status (OR 5.7, p=0.04). Analyses restricted to the 70 subjects with Definite AD showed that IML+OML staining (compared to OML-only) was associated with higher Braak stage and earlier age of death. CONCLUSIONS: Phospho-tau deposition in AD occurs within IML and/or OML. Prominent IML involvement is associated with earlier age of death in AD. Support included NIH/NIA grant #P50AG08702 and the Taub Institute. Disclosure: Dr. Seifan has nothing to disclose. Dr. Noble has nothing to disclose. Dr. Mez has nothing to disclose. Dr. Marder has received personal compensation in an editorial capacity for Current Neuroscience. Dr. Marder has received research support from the National Institutes of Health, Michael J Fox Foundation, Parkinson Disease Foundation, CHDI Foundation, and Huntington9s Disease Soceity of America. Dr. Honig has received personal compensation for activities with Johnson & Johnson, Janssen, and the Gerson Lehman Group. Dr. Honig has received personal compensation in an editorial capacity for American Medical Association/Archives of Neurology. Dr. Honig has received research support from Allon, Baxter, Bristol-Myers Squibb Company, Elan Corporation, Genentech, Inc., Eli Lilly & Company, Janssen, and Pfizer Inc.
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