The Effects of Long-Term Treatment with Metrifonate, a Cholinesterase Inhibitor, on Cholinergic Activity, Amyloid Pathology, and Cognitive Function in APP and PS1 Doubly Transgenic Mice

Alzheimer’s disease (AD) is accompanied by prominent behavioural disturbances. They cause significant distress for both caregivers and patients and can play a major role in the decision to institutionalise AD patients. Recent evidence suggests that cholinergic deficiencies not only contribute to the memory and cognitive abnormalities of AD but are also responsible for some behavioural abnormalities seen over the course of the disease. In this study we assessed the ability of rivastigmine, a pseudo-irreversible cholinesterase inhibitor, to improve behavioural and psychopathologic symptoms in AD. The analysis included 34 patients present in the Germanarm of the international study B303 who received and completed long-term treatment with rivastigmine in the open-label study B305. Assessments of behaviour and psychopathological symptoms were performed using the behavioural component of the Clinicians Interview Based Impression of Change Plus (CIBIC-Plus). Results show that long-term treatment with rivastigmine can slow the progression of behavioural and psychopathological symptoms of AD. Behavioural symptoms showing stabilisation included aggressiveness, activity disturbances, hallucinations and paranoid features. Results also suggest that patients treated earlier with rivastigmine may attain a greater benefit compared with patients whose treatment is delayed 6 months. Further studies examining the effects of rivastigmine on behavioural disturbances in AD are therefore warranted.

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Increased expression of the neuropeptide Y receptor Y1 gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone

Journal of Neurochemistry ◽

10.1046/j.1471-4159.2001.00559.x ◽

2008 ◽

Vol 79 (2) ◽

pp. 417-425 ◽

Cited By ~ 24

Author(s):

Gianna Ferrara ◽

Mariangela Serra ◽

Francesca Zammaretti ◽

Maria Giuseppina Pisu ◽

GianCarlo Panzica ◽

...

Keyword(s):

Transgenic Mice ◽

Neuropeptide Y ◽

Term Treatment ◽

Medial Amygdala ◽

Neuropeptide Y Receptor ◽

Long Term Treatment

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140. Long-term treatment with quetiapine improves cognitive function in schizophrenia

Biological Psychiatry ◽

10.1016/s0006-3223(00)00402-9 ◽

2000 ◽

Vol 47 (8) ◽

pp. S42 ◽

Cited By ~ 4

Author(s):

S.E. Purdon ◽

A. Malla ◽

A. Labelle ◽

W. Litt

Keyword(s):

Cognitive Function ◽

Term Treatment ◽

Long Term Treatment

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068 Evaluation of the long-term treatment effect of teriflunomide on cognitive outcomes and association with brain volume change: data from temso and its extension study

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.67 ◽

2018 ◽

Vol 89 (6) ◽

pp. A28.1-A28 ◽

Cited By ~ 1

Author(s):

Till Sprenger ◽

Jeannette Lechner-Scott ◽

Maria P Sormani ◽

Jerry S Wolinsky ◽

Jens Wuerfel ◽

...

Keyword(s):

Cognitive Function ◽

Volume Change ◽

Brain Volume ◽

Term Treatment ◽

Cognitive Outcomes ◽

Link Type ◽

Brain Volume Loss ◽

Long Term Treatment ◽

Z Scores

IntroductionIn a blinded SIENA (Structural Image Evaluation using Normalisation of Atrophy) analysis of TEMSO (NCT00134563), teriflunomide significantly reduced brain volume loss (BVL) over 2 years vs placebo. Further analysis indicated a strong correlation between 2 year BVL and disability worsening, showing better disability outcomes for patients with lower rates of BVL. Here, we explore the relationship between BVL and long-term changes in cognitive function in TEMSO and its extension (NCT00803049).MethodsThe effect of teriflunomide on cognitive function was assessed by change from baseline in Paced Auditory Serial Addition Test (PASAT)−3 scores in the TEMSO core (n=1086) and extension (n=740) studies. To evaluate change in PASAT-3 scores over 5 years, the TEMSO population was categorised into groups defined by percentage brain volume change from baseline to Year 2 (assessed by SIENA).ResultsAdjusted mean changes from baseline to Week 96 in PASAT-3 raw/Z-scores were –0.265/–0.022 and 0.870/0.073 for placebo and teriflunomide 14 mg, respectively (difference vs placebo, p=0.0435 in both instances). Long-term improvements in PASAT-3 Z-scores were observed with teriflunomide 14 mg treatment: mean (SD) changes from baseline at Weeks 156 and 276 were 0.194 (0.634) and 0.200 (0.677), respectively. Mean (SD) units of change from baseline in raw PASAT-3 scores for teriflunomide 14 mg–treated patients at Weeks 156 and 276 were 2.36 (7.73) and 2.43 (8.24), respectively. In an association analysis, the group with least BVL from baseline to Year 2 demonstrated a significant improvement in PASAT-3 score with teriflunomide treatment over 5 years vs the group with most BVL.ConclusionTeriflunomide significantly improved PASAT-3 performance vs placebo over 5 years in the TEMSO core and extension studies. Slower rates of BVL over 2 years correlated with better long-term PASAT-3 improvement. This study suggests that BVL earlier in the disease course predicts longer-term cognitive function.Study supportSanofi.

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