Long-term exposure to air pollution and the incidence of dementia, Alzheimer’s disease and cognitive impairment

ObjectiveTo investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.DesignRetrospective cohort study using primary care data.Setting75 Greater London practices.Participants130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.Primary and secondary outcome measuresA first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.Results2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5specifically from primary traffic sources only and Lnight, but only NO2and PM2.5remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.ConclusionsWe have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.

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Air Pollution as Risk Factor for Mental Disorders: In Search for a Possible Link with Alzheimer’s Disease and Schizophrenia

Advances in Alzheimer’s Disease - Alzheimer’s Disease and Air Pollution ◽

10.3233/aiad210043 ◽

2021 ◽

Author(s):

Luigi Attademo ◽

Francesco Bernardini

Keyword(s):

Mental Health ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Air Pollution ◽

Risk Factor ◽

Air Pollutants ◽

Epidemiological Studies ◽

Increased Risk ◽

The Central Nervous System

As a global problem that has increasingly been causing worldwide concern, air pollution poses a significant and serious environmental risk to health. Risks of cardiovascular and respiratory diseases, as well as various types of cancer, have been consistently associated with the exposure to air pollutants. More recently, various studies have also shown that the central nervous system is also attacked by air pollution. Air pollution appears to be strongly associated with a higher risk of cognitive defects, neurodevelopmental (e.g., schizophrenia) and neurodegenerative (e.g., Alzheimer’s disease) disorders. Subjects with schizophrenia, as well as subjects with Alzheimer’s disease, experience a variety of neuropsychological deficits and cognitive impairments. This determines an adverse effect on social and professional functioning, and it contributes to the long-term disease burden. However, no final conclusions have been drawn on the matter of the direct relationship between schizophrenia and Alzheimer’s disease. In recent years, the topic of urbanicity and mental health has become increasingly important. Urban exposure to environmental toxins and pollution is currently described as a reliable risk factor for schizophrenia and other psychoses, and it has been demonstrated more and more how exposure to air pollutants is associated with increased risk of dementia. Pathways by which air pollution can target and damage the brain, leading to an increased risk for developing schizophrenia and Alzheimer’s disease, are multiple and complex. Results from epidemiological studies suggest potential associations, but are still insufficient to confirm causality. Further studies are needed in order to verify this hypothesis. And if confirmed, the clinical implications could be of substantial relevance for both public and mental health.

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Ozone, Particulate Matter, and Newly Diagnosed Alzheimer’s Disease: A Population-Based Cohort Study in Taiwan

Advances in Alzheimer’s Disease - Alzheimer’s Disease and Air Pollution ◽

10.3233/aiad210002 ◽

2021 ◽

Author(s):

Chau-Ren Jung ◽

Yu-Ting Lin ◽

Bing-Fang Hwang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Air Pollution ◽

Cohort Study ◽

Particulate Matter ◽

Proportional Hazards ◽

Newly Diagnosed ◽

Hazards Model

Several studies with animal research associate air pollution in Alzheimer’s disease (AD) neuropathology, but the actual impact of air pollution on the risk of AD is unknown. Here, this study investigates the association between long-term exposure to ozone (O3) and particulate matter (PM) with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5), and newly diagnosed AD in Taiwan. We conducted a cohort study of 95,690 individuals’ age ≥ 65 during 2001–2010. We obtained PM10 and O3 data from Taiwan Environmental Protection Agency during 2000–2010. Since PM2.5 data is only accessible entirely after 2006, we used the mean ratio between PM2.5 and PM10 during 2006–2010 (0.57) to estimate the PM2.5 concentrations from 2000 to 2005. A Cox proportional hazards model was used to evaluate the associations between O3 and PM2.5 at baseline and changes of O3 and PM2.5 during the follow-up period and AD. The adjusted HR for AD was weakly associated with a raised concentration in O3 at baseline per increase of 9.63 ppb (adjusted HR 1.06, 95% confidence interval (CI) 1.00–1.12). Further, we estimated a 211% risk of increase of AD per increase of 10.91 ppb in O3 over the follow-up period (95% CI 2.92–3.33). We found a 138% risk of increase of AD per increase of 4.34 μg/m3 in PM2.5 over the follow-up period (95% CI 2.21–2.56). These findings suggest long-term exposure to O3 and PM2.5 above the current US EPA standards are associated with increased the risk of AD.

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Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young

Environmental Research ◽

10.1016/j.envres.2020.110087 ◽

2020 ◽

Vol 191 ◽

pp. 110087 ◽

Cited By ~ 1

Author(s):

Lilian Calderón-Garcidueñas ◽

Ana Karen Torres-Solorio ◽

Randy J. Kulesza ◽

Ricardo Torres-Jardón ◽

Luis Oscar González-González ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Air Pollution ◽

Cognitive Impairment ◽

Historical Development

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Associations Between Long Term Exposure to Air Pollution and the Incidence of Dementia and Cognitive Impairment in a Canadian Prospective Cohort Study

10.22215/etd/2016-11426 ◽

2016 ◽

Author(s):

Yanjiang Yu

Keyword(s):

Air Pollution ◽

Cohort Study ◽

Cognitive Impairment ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Incidence Of Dementia

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Synaptic Plasticity and Oscillations in Alzheimer’s Disease: A Complex Picture of a Multifaceted Disease

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.696476 ◽

2021 ◽

Vol 14 ◽

Author(s):

Yuniesky Andrade-Talavera ◽

Antonio Rodríguez-Moreno

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Neuronal Network ◽

Brain Plasticity ◽

Network Dynamics ◽

Long Term Potentiation ◽

High Frequency Stimulation ◽

Neuronal Network Dynamics

Brain plasticity is widely accepted as the core neurophysiological basis of memory and is generally defined by activity-dependent changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). By using diverse induction protocols like high-frequency stimulation (HFS) or spike-timing dependent plasticity (STDP), such crucial cognition-relevant plastic processes are shown to be impaired in Alzheimer’s disease (AD). In AD, the severity of the cognitive impairment also correlates with the level of disruption of neuronal network dynamics. Currently under debate, the named amyloid hypothesis points to amyloid-beta peptide 1–42 (Aβ42) as the trigger of the functional deviations underlying cognitive impairment in AD. However, there are missing functional mechanistic data that comprehensively dissect the early subtle changes that lead to synaptic dysfunction and subsequent neuronal network collapse in AD. The convergence of the study of both, mechanisms underlying brain plasticity, and neuronal network dynamics, may represent the most efficient approach to address the early triggering and aberrant mechanisms underlying the progressive clinical cognitive impairment in AD. Here we comment on the emerging integrative roles of brain plasticity and network oscillations in AD research and on the future perspectives of research in this field.

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Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

The British Journal of Psychiatry ◽

10.1192/bjp.bp.110.080044 ◽

2011 ◽

Vol 198 (5) ◽

pp. 351-356 ◽

Cited By ~ 184

Author(s):

Orestes V. Forlenza ◽

Breno S. Diniz ◽

Márcia Radanovic ◽

Franklin S. Santos ◽

Leda L. Talib ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Lithium Treatment ◽

Amnestic Mild Cognitive Impairment ◽

Disease Assessment ◽

Short Term Treatment ◽

Disease Modifying

BackgroundTwo recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.AimsTo evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).MethodForty-five participants with aMCI were randomised to receive lithium (0.25–0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ42), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.ResultsLithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.ConclusionsThe present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

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Citicoline in the Treatment of Mild Cognitive Impairment in Blood Relatives of Patients with Alzheimer’s Disease: Immediate and Long-Term Effects of Course Therapy

Psychiatry ◽

10.30629/2618-6667-2021-19-4-42-51 ◽

2021 ◽

Vol 19 (4) ◽

pp. 42-51

Author(s):

N. D. Seleznеva ◽

I. F. Roshchina ◽

E. V. Ponomareva ◽

S. Iv. Gavrilova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Functioning ◽

Cognitive Dysfunction ◽

Therapeutic Effects ◽

Long Term Effects ◽

Voluntary Attention

The aim was to study immediate and long-term (post-therapeutic) effects of a three-month course of therapy with citicoline in 1st-degree relatives of patients with Alzheimer’s disease (AD). All the included relatives of patients with AD revealed signs of minimal cognitive dysfunction (MCD) and mild cognitive decline syndrome (MCI — Mild Cognitive Impairment, ICD-10 code F06.7). Study participants: the study involved 90 first-degree relatives: 24 with MCI and 66 with MCD. Study design: an open-label comparative multidisciplinary study of the six-month dynamics of cognitive functioning of two groups of relatives who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of relatives with MCI syndrome and MKD were compared with the indicators at the end of the three-month course of therapy with citicoline at a daily dose of 1000 mg as well as 3 months after the end of the course of treatment. Methods: clinical, psychopathological, neuropsychological, psychometric, genetic, statistical ones. Results: а significant positive effect of the course therapy with citicoline on the cognitive impairment of 1st degree AD-patients’ relatives with minimal cognitive dysfunction and more pronounced cognitive impairments met the diagnostic criteria for MCI syndrome has been found. A significantly greater value of both immediate and long-term therapeutic effect of MKD compared with MCI in relatives was established by psychometric and neuropsychological indicators characterizing voluntary memorization of verbal and visual stimuli, optical and spatial activity, voluntary attention, and associative verbal thinking. Conclusion: the results of the study can be used as the basis for a model of prevention of the progression of cognitive deficit and the development of dementia in persons with a high risk of developing AD, i.e. in individuals with both genetic risk and signs of cognitive impairment.

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Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22052283 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2283

Author(s):

Yu-Jung Cheng ◽

Chieh-Hsin Lin ◽

Hsien-Yuan Lane

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Early Stage ◽

Amyloid Β ◽

Tau Proteins ◽

And Oxidative Stress

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.

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