Safety and Efficacy of Rivastigmine in Adolescents with Down Syndrome: A Preliminary 20-Week, Open-Label Study

Heller, James H.; Spiridigliozzi, Gail A.; Crissman, Blythe G.; Sullivan, Jennifer; Eells, Rebecca L.; Li, Jennifer S.; Doraiswamy, P. Murali; Krishnan, Kamini; Kishnani, Priya S.

doi:10.1089/cap.2006.16.755

Cited by 39 publications

(41 citation statements)

References 15 publications

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“…The Corsi Block Tapping Forward (sum of the number of digits in trials remembered correctly) measures visuospatial memory (Shapiro et al, 1992). The NEPSY Visual Attention subtest assesses visual attention (Visual Attention Accuracy) and processing speed (Visual Attention Time) and is appropriate in DS (Heller et al, 2006). …”

Section: Methodsmentioning

confidence: 99%

Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome

Hartley

Handen

Devenny

et al. 2017

Neurobiology of Aging

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Adults with Down syndrome (DS) have a high incidence of Alzheimer’s disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-β accumulation via the PET tracer [11C] Pittsburgh compound B (PiB) across two data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex and anterior ventral striatum. Across the two cycles, 14 (27.5%) participants were consistently PiB+, 31 (60.8%) were consistently PiB−, and 6 (11.7%) converted from PiB− at Cycle 1 to PiB+ at Cycle 2. Increased global amyloid-β was related to decline in verbal episodic memory, visual episodic memory, executive functioning, and fine motor processing speed. Participants who were consistently PiB+ demonstrated worsening of episodic memory, whereas participants who were consistently PiB− evidenced stable or improved performance. Amyloid-β accumulation may be a contributor to or biomarker of declining cognitive functioning in preclinical AD in DS.

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Section: Methodsmentioning

confidence: 99%

Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome

Hartley

Handen

Devenny

et al. 2017

Neurobiology of Aging

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“…The VABS‐II is a commonly used measure of adaptive behavior in individuals with ID. It has also been included as an efficacy measure in a number of clinical trials including individuals with DS (Heller et al, ; Kishnani et al, ; Spiridigliozzi et al, ). The VABS‐II Survey Interview Form was used in the present study to measure participants' level of adaptive behavior, as reported by their parent or primary caregiver.…”

Section: Introductionmentioning

confidence: 99%

Adaptive behavior in adolescents and adults with Down syndrome: Results from a 6‐month longitudinal study

Spiridigliozzi

Goeldner

Edgin

et al. 2018

American J of Med Genetics Pt A

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Measures of adaptive behavior are important in the assessment and treatment of individuals with intellectual disabilities (ID). The purpose of the current study was to evaluate the stability of an established and a novel measure of adaptive behavior over time, and their suitability as outcome measures in clinical trials targeting individuals with Down syndrome (DS). This 6-month, longitudinal, noninterventional, multinational study included adolescents (12-17 years) and adults (18-30 years) with DS. Participants were from seven countries (11 different sites) with English, Spanish and French as their native language. The Vineland Adaptive Behavior Scales-II (VABS-II) and a newly developed Clinician Global Impression (CGI) scale were administered at baseline, 1 and 6 months. Adults had lower composite standard scores on all domains of the VABS-II compared with adolescents. The communication domain was a weakness relative to the socialization and daily living skills domains on the VABS-II and the CGI-Severity scale. These findings were stable over 6 months, as exhibited by high intraclass correlations (>0.75). These results provide valuable baseline data for use in trial design and endpoint selection for studies including individuals with DS. ClinicalTrials.gov identifier: NCT01580384. K E Y W O R D S adaptive behavior, CGI-I, CGI-S, Down syndrome, intellectual disability, VABS-II

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“…Alzheimer's disease, Down's syndrome, Parkinson's disease, and schizophrenia are generally characterized by progressive diminution in cognitive function associated with the loss of cholinergic neurons and synapses in the brain 1–5. For example, in Alzheimer's disease, the severity of cognitive dysfunction is correlated with loss of cholinergic synaptic elements in the cortex and subcortical brain areas 6–12.…”

Section: Introductionmentioning

confidence: 99%

Synthesis andin VitroBiological Evaluation of Carbonyl Group-Containing Inhibitors of Vesicular Acetylcholine Transporter

Efange¹,

Khare²,

Hohenberg³

et al. 2010

J. Med. Chem.

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To identify selective high-affinity inhibitors of the vesicular acetylcholine transporter (VAChT), we have interposed a carbonyl group between the phenyl and piperidyl groups of the prototypical VAChT ligand vesamicol, and its more potent analogues benzovesamicol and 5-aminobenzovesamicol. Of 33 compounds synthesized and tested, six display very high affinity for VAChT (Ki, 0.25 – 0.66 nM) and greater than 500-fold selectivity for VAChT over σ1 and σ2 receptors. Twelve compounds have high affinity (Ki, 1.0–10 nM) and good selectivity for VAChT. Furthermore, three halogenated compounds, namely, trans-3-[4-(4-fluorobenzoyl)piperidinyl]-2-hydroxy-1,2,3,4-tetrahydronaphthalene (28b) (Ki = 2.7 nM, VAChT/sigma selectivity index = 70), trans-3-[4-(5-iodothienylcarbonyl)piperidinyl]-2-hydroxy-1,2,3,4-tetrahydronaphthalene (28h) (Ki = 0.66 nM, VAChT/sigma selectivity index = 294), and 5-amino-3-[4-(p-fluorobenzoyl)piperidinyl]-2-hydroxy-1,2,3,4,-tetrahydronaphthalene (30b) (Ki = 2.40 nM, VAChT/sigma selectivity index = 410) display moderate to high selectivity for VAChT. These three compounds can be synthesized with the corresponding radioisotopes so as to serve as PET/SPECT probes for imaging the VAChT in vivo.

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Safety and Efficacy of Rivastigmine in Adolescents with Down Syndrome: A Preliminary 20-Week, Open-Label Study

Cited by 39 publications

References 15 publications

Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome

Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome

Adaptive behavior in adolescents and adults with Down syndrome: Results from a 6‐month longitudinal study

Synthesis andin VitroBiological Evaluation of Carbonyl Group-Containing Inhibitors of Vesicular Acetylcholine Transporter

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