Anticholinergic alzheimer's
214429379
12.30 Do anticholinergic drugs increase alzheimer's pathology in parkinson's patients? A retrospective post mortem investigation
Introduction Recent studies have highlighted the accumulated use of anticholinergic drugs is associated with an increased risk of dementia, and many of those are used for symptomatic management in Parkinson's disease (PD) Unfortunately, the only available post mortem study investigating the effect of anticholinergic agents on Alzheimer's pathology burden suffers from several methodological limitations. Therefore, we aimed to validate if cumulative use of anticholinergic medication will increase Alzheimer's pathologies in the post mortem PD brains. Material and methods Retrospective case note analysis was carried out on 54 selected PD cases from the Parkinson's UK Brain Bank and cases were stratified into no, low and high anticholinergic burden using literature based anticholinergic scores. Association of anticholinergic burden and Alzheimer's pathology in post mortem tissues was analysed with logistic regression modelling. Results A higher anticholinergic burden is associated with a greater tau burden in entorhinal cortex in PD cases (OR=2.21) Interestingly, a high anticholinergic burden decreases the odds of amyloid beta presence in the anterior hippocampus (OR=0.127) entorhinal cortex (OR=0.124) and frontal cortex (OR=0.113) of PD cases. Conclusion We have demonstrated that anticholinergic drugs have varying effect on Alzheimer's pathology in post mortem PD brain tissues. Complex mechanism is probably involved and require further studies.
Journal of Neurology, Neurosurgery, and Psychiatry
Alan King Lun Liu Yau Mun Lim Ronald K B Pearce Steve Gentleman
204761467
ASSOCIATION OF ANTICHOLINERGIC MEDICATION USE WITH IN VIVO ALZHEIMER'S DISEASE PATHOLOGIES
the pre dementia stage (LOMCI>EOMCI) EOAD had greater GM FW increases in the parietal/precuneus and middle temporal regions than LOAD (Fig. 3) Lastly, parietal GM FW increases contributed to global cognitive impairment in MCI while parietal and temporalWM abnormalities and GM thinning related to lower MoCA in dementia (Table 1) Conclusions: Our study revealed differential patterns of GM and WM macro/microstructural changes in earlyand late onset AD and MCI. Findings suggested that GM microstructural changes appeared earlier than cortical thinning and were better associated with cognitive decline. The combined WM and GM microstructural assays could help differential diagnosis and early detection in preclinical and prodromal stages of neurodegeneration. rday, July 13, 2019
Alzheimer's Dementia
Jun Ho Lee Min Soo Byun Dahyun Yi So Yeon Jeon Gijung Jung Han Na Lee Bo Kyung Sohn Jun-Young Lee Seung-Ho Ryu Dong Woo Lee Dong Young Lee
204758993
ASSOCIATION OF ANTICHOLINERGIC MEDICATION USE WITH IN VIVO ALZHEIMER'S DISEASE PATHOLOGIES
Background: Vascular disease pathology is a common comorbidity in multiple degenerative diseases and measured as white matter hyperintensities (WMH) on T2 images. The origin and specific role of WMH in different diseases is incompletely understood. In this work, we compared WMH burden in Alzheimers (AD) and Parkinsons disease (PD) We tested association with cerebral blood flow (CBF) as a marker of vascular insufficiency and mean diffusivity (MD) in white matter as a marker of axonal/myelin rarefaction. We also evaluated the association of WMH burden, CBF, and MD with the administered cognitive battery. Methods: 114 (Table 1) individuals underwent FLAIR, pCASL, and DTI MRI. Subjects were recruited at the local ADRC and Udall Center and analyzed separately. Lobar WMH burden was calculated and subdivided into lobar periventricular (PVH) and deep (DH) WMH. We tested the hypothesis that PVH and DH burden were associated with MD and CBF respectively in both diseases. Furthermore, we tested association of all cognitive tests (MoCA, MiNT, CATFLU, CRAFT) that were available for all subjects with hypothesized lobar WMH burden, CBF, and MD. Results: We show that AD subjects have a significantly higher PVH burden than NC especially in the frontal and parietal lobes as well as a higher frontal DH burden (Figure 1) No association was detected between PVH and MD or between DH and CBF. Low CATFLU scores were significantly associated with higher temporo frontal CBF and temporal MD (Figure 2) Low MoCA scores were associated with high parieto temporal MD. For PD subjects, no significant difference in WMH burden was observed compared to NC. WMH burden was associated with MD in PD. No association was observed with lobar CBF. Temporal WMH was associated with MoCA, CATFLU and MiNT in PD (Figure 3) All tests were adjusted for age and sex. Conclusions: WMH burden is higher in AD than PD.CBF was associated with cognitive symptoms in AD not PD. While commonly associated with executive functioning, we found associations of WMH andMDwith cognition only in PD. Vascular pathology manifests differently in different degenerative diseases indicating that it may play a more mechanistic role in AD than just being a comorbidity.
Alzheimer's Dementia
Jun Ho Lee Min Soo Byun Dahyun Yi So Yeon Jeon Gijung Jung Han Na Lee Bo Kyung Sohn Jun-Young Lee Seung-Ho Ryu Dong Woo Lee Dong Young Lee
2077621
Midlife anticholinergic drug use, risk of Alzheimer's disease, and brain atrophy in community dwelling older adults
We examined how long term anticholinergic (AC) drug use beginning at midlife affects risk of Alzheimer's disease (AD) and rates of brain atrophy in cognitively normal older adults.
Alzheimer's dementia
Yi-Fang Chuang Palchamy Elango Christopher E Gonzalez Madhav Thambisetty
3481250
Anticholinergic Exposure and Risk of Pneumonia in Persons with Alzheimer's Disease: A Nested Case Control Study.
BACKGROUND Risk of pneumonia is increased in persons with Alzheimer's disease (AD) In some studies, anticholinergic drugs (AC) have been associated with an increased pneumonia risk. OBJECTIVE We analyzed the risk of pneumonia associated with ACs in persons with AD. METHODS We performed a nested case control study using register based data from a Finnish nationwide MEDALZ cohort including all community dwelling persons diagnosed with AD during 2005 2011. Cases were identified based on pneumonia diagnoses (n 12,442) from hospital discharge and causes of death registers. Up to two controls without pneumonia were matched based on time since AD diagnoses, age, and gender for each case; AC use was measured using Anticholinergic Drug Scale. RESULTS Use of AC was associated with an increased risk of pneumonia (adjusted odds ratio (OR) 1.36, 95% confidence interval (CI) 1.29 1.43) However, there was no increased pneumonia risk in persons using level 3 ACs. Incident use was associated with higher risk of pneumonia (OR 2.68, 95% CI 2.15 3.34) than prevalent use (OR 1.48, 95% CI 1.40 1.57) Among persons using cholinesterase inhibitors (AChEIs) risk of pneumonia was increased in persons using also ACs (OR 1.53, 95% CI 1.41 1.66) CONCLUSION ACs were associated with an increased risk of pneumonia in persons with AD, especially at the time of initiation of these drugs. AC use was associated with increased pneumonia risk also in persons using AChEIs. This risk should be carefully considered when treating AD patients.
Journal of Alzheimer's disease JAD
Pasi Lampela Anna-Maija Tolppanen Antti Tanskanen Jari Tiihonen Sirpa Hartikainen Heidi Taipale
53253968
CONCOMITANT USE OF ANTICHOLINERGIC MEDICATION ATTENUATES BENEFITS OF CHOLINESTERASE INHIBITORS IN ALZHEIMER'S DISEASE: A LARGE COHORT STUDY OF SURVIVAL AND COGNITIVE FUNCTION
Figure. Comparison of longitudinal change in MMSE Babak Hooshmand, Helga Refsum, A. David Smith, Ingemar K areholt, Christine von Arnim, Erika Jonsson Laukka, Lars BEURackman, Laura Fratiglioni, Miia Kivipelto, Karolinska Institutet, Stockholm, Sweden; Ulm University Hospital, Ulm, Germany; Oslo University, Oslo, Norway; Oxford University, Oxford, United Kingdom; Karolinska Institute, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden; Kuopio University Hospital, Kuopio, Finland; National Institute for Health and Welfare, Helsinki, Finland; Karolinska Institutet Stockholm University, Stockholm, Sweden; University of Eastern Finland, Kuopio, Finland. Contact e mail: Babak.Hooshmand@ki.se
Alzheimer's Dementia
Christoph Mueller Brendon Stubbs S Banerji Robert J Stewart Gayan Perera
33391496
Hypothesis of Endogenous Anticholinergic Activity in Alzheimer's Disease
In this article, we review and repropose our hypothesis of the endogenous appearance of anticholinergic activity (AA) in Alzheimer's disease (AD) First, we introduce our previous articles and speculate that, because acetylcholine (ACh) regulates both cognitive function and inflammation, downregulation of this neurotransmitter causes upregulation of the inflammatory system. AA then appears endogenously with the production of cytokines and the downregulation of ACh in AD. To support our hypothesis, we present a female AD patient whose AA was considered to occur endogenously through her AD pathology. Her serum anticholinergic activity (SAA) was positive at her first visit to our memory clinic, was negative at the 1 year and 2 year follow up visits, and had become positive again by 3 years. We speculate that the initial positive SAA was related to her AD pathology plus mental stress, and that her SAA at 3 years was related to her AD pathology only. Consequently, we believe that 2 patterns of SAA positivity (and therefore AA) exist. One occurs when the downregulation of ACh reaches a critical level, and the other occurs with the addition of some other factor such as medication, induced illness or mental stress that causes AA to affect AD pathology. Finally, we consider the pharmacotherapy of AD based on the proposed hypothesis and conclude that cholinesterase inhibitors can be used to prevent rapid disease progression, whereas N methyl D aspartate receptor antagonists should be reserved for the treatment of AD that is already in a stage of rapid progression. We also propose a staging schema for patients with AD.
Neurodegenerative Diseases
Kimiko Konishi Koji Hori Masayuki Tani Hiroi Tomioka Yuka Kitajima Norihisa Akashi Atsuko Inamoto Kenzo Kurosawa Haijime Yuda Takahiro Hanashi Hiromi Ouchi Misa Hosoi Mitsugu Hachisu
24486746
Does Anticholinergic Activity Affect Neuropathology Implication of Neuroinflammation in Alzheimer's Disease
One characteristic neuropathological feature of Alzheimer's disease (AD) is profound neuronal loss in the nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex. Clinically, anticholinergic activity causes a decline in cognitive function and increases the risk of dementia, thus possibly enhancing AD pathologies and neurodegeneration. Until now there has been insufficient human neuropathological data to support this conclusion. Experimental studies using a tauopathy mouse model demonstrated anticholinergics enhanced tau pathology and neurodegeneration corresponding to central anticholinergic activity. Additionally, donepezil, a cholinesterase inhibitor, ameliorated tau pathology and neurodegeneration in the same mouse model. These results indicate the balance between cholinergic and anticholinergic activities might affect neurodegeneration. Importantly, neurodegeneration observed in the mouse model seemed to correspond to the distribution of microglial activation, and it was reported that neuroinflammation plays an important role in the pathomechanism of AD, while anticholinergic activity augments inflammatory responses. Moreover, some studies indicated b amyloid itself depletes cholinergic function similarly to anticholinergic activity. Thus, anticholinergic activity might initiate and/or accelerate AD pathology. Limited human data support the conclusion that anticholinergic activity enhances AD related neuropathology and neurodegeneration. However, experimental data from a tauopathy mouse model indicated anticholinergic activity might enhance neurodegeneration with enhanced neuroinflammation including microglial activation.
Neurodegenerative Diseases
Yasumasa Yoshiyama Ayako Kojima Kimiko Itoh Sagiri Isose Mizuho Koide Koji Hori Kimihito Arai
25637111
Assessment of Cognitive Dysfunction Caused by Anticholinergic Burden in Japanese Alzheimer's Disease Patients, Using the Most Commonly Used Scales in Japan.
Anticholinergic activity (AA) is generally thought to cause cognitive dysfunction, especially in Alzheimer's disease (AD) one of the neurocognitive disorders related to memory disturbances. Therefore, it is important to evaluate cognitive functions to determine whether they are associated with anticholinergic burden. In Japan, the most frequently used cognitive scale for evaluating cognitive functions is the revised version of Hasegawa's Dementia Rating Scale (HDS R) However, the relationship between anticholinergic burden and cognitive functions has not been previously examined using the HDS R. Therefore, here we used the HDS R to evaluate the relationship between serum anticholinergic activity (SAA) and cognitive functions in 76 patients with AD, 26 of whom had positive SAA [SAA with a mean of 4.14 2.70 nM. Total scores for orientations to time and place, registration, and recall were significantly lower in the SAA group than in the SAA group (P 0.05) suggesting potential relationships between SAA and disorientations to time and place in current surroundings as well as memory disturbances. Thus, the disorientations to time and place might explain the clinical features of confusion in current surroundings caused by anticholinergic burden in AD.
Nihon shinkei seishin yakurigaku zasshi Japanese journal of psychopharmacology
Kimiko Konishi Koji Hori Mitsugu Hachisu Hiroi Tomioka Masayuki Tani Misa Hosoi Yuka Kitajima Atsuko Inamoto Akira Iwanami
1668073
Beyond the Hypothesis of Serum Anticholinergic Activity in Alzheimer's Disease: Acetylcholine Neuronal Activity Modulates Brain Derived Neurotrophic Factor Production and Inflammation in the Brain
The brain of Alzheimer's disease (AD) patients is characterized by neurodegeneration, especially an acetylcholine (ACh) neuronal deficit with accumulation of b amyloid protein, which leads to oxygen stress and inflammation. The active oxygen directly damages the neuron by increasing intracellular Ca2+ The inflammation is due to activation of the microglia, thereby producing cytokines which inhibit the production of brain derived neurotrophic factor (BDNF) As the BDNF acts by neuronal protection, synaptogenesis and neurogenesis, the reduction of BDNF in the brain of AD patients worsens the symptoms of AD. On the other hand, treatment of AD patients with a cholinesterase inhibitor enhances ACh activity and inhibits inflammation. Then the expression of BDNF is restored and neuroprotection reestablished. However, there are several reports which showed controversial results concerning the relationship between BDNF and AD. We speculate that BDNF is related to some neurocognitive process and reflects neuronal activity in other neurodegenerative and neuropsychiatric disorders and that in the mild cognitive impairment stage, BDNF and choline acetyltransferase (ChAT) activities are hyperactivated because of a compensatory mechanism of AD pathology. In contrast, in the mild stage of AD, BDNF and ChAT activity are downregulated.
Neurodegenerative Diseases
Mitsugu Hachisu Kimiko Konishi Misa Hosoi Masayuki Tani Hiroi Tomioka Atsuko Inamoto Sousuke Minami Takuji Izuno Kaori Umezawa Kentaro Horiuchi Koji Hori