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Coffee Decreases Parkinson’s Tremors in Men, Study Suggests

coffee, tremors and Parkinson's

Drinking coffee may reduce tremors in Parkinson’s disease patients, but only among men, a recent study suggests.

The study, “Sex-dependent Effects of Coffee Consumption on Newly Diagnosed Parkinson’s Disease,” was published recently in the journal BMC Neurology.

There is some evidence that drinking coffee reduces the risk of developing Parkinson’s disease, but the effect of coffee on motor symptoms in people who already have been diagnosed with Parkinson’s is less clear.

In this study, researchers recruited Parkinson’s patients (137 women, 147 men) and divided them into two groups: coffee drinkers (204 people), which included anyone who drinks coffee regularly, or used to, even if they don’t anymore, and; non-coffee drinkers (80 people) who never regularly drank coffee.

Compared to the non-coffee drinkers, coffee drinkers were disproportionately younger, male, better-educated, and were younger at symptom onset. Coffee drinkers had less motor impairment, as demonstrated by lower scores on the motor section of the Unified Parkinson Disease Rating Scale (UPDRS; 19.46 vs. 22.84); this included significantly lower scores for tremor (2.48 vs. 3.64), bradykinesia (slow movement; 2.48 vs. 10.83) and gait and posture (0.78 vs. 1.16).

Of note, resting tremor occurs when a person’s hands, arms, or legs shake even when they are at rest; action tremor occurs with the voluntary movement of a muscle.

When the researchers included other factors (age, sex, etc.) in their model, most of these differences were no longer statistically significant. However, tremor scores were still significantly lower among coffee drinkers. More specifically, coffee drinkers had significantly lower scores for tremors at rest (1.49 vs. 2.41), whereas scores for action tremors were not very much  different between the two groups once other variables were taken into account.

Furthermore, this association was dose-dependent. That is, the more coffee participants reported drinking, the lower their tremor scores tended to be.

Researchers then divided the patients by sex and performed a similar analysis. Interestingly, tremor scores were significantly lower among male coffee drinkers as compared to male non-coffee drinkers, but this association was not statistically significant for females. This suggests sex-dependent differences on the effects of coffee in Parkinson’s patients.

The researchers speculated that such differences may be attributable to hormones that are typically present at different levels between the sexes, most notably estrogen. But further research will be needed to determine whether this idea holds water.

“Coffee consumption and tremor severity are inversely related in male patients with de novo [Parkinson’s disease],” the researchers wrote. “Further investigations are needed to reveal the exact causal relationship between coffee consumption and tremor in [Parkinson’s disease] patients,” they added.

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Mouse Studies Suggest Protective Effects of Caffeine in Parkinson’s Disease

caffeine and Parkinson's

Two new studies in mice suggest that caffeine might have protective effects in the brains of Parkinson’s disease patients.

The studies, “Chronic Caffeine Treatment Modulates  Disease Progression in a Transgenic Alpha-Synuclein Prion-Like Spreading Mouse Model of Parkinson’s Disease,” and “Chronic Caffeine Treatment Reverses A-Synuclein-Induced Cognitive Impairment With Enhanced Dendritic Spine Density and Morphology in Mice,” will be presented during the 14th​ International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders, March 26-31 in Lisbon, Portugal.

Previous epidemiological studies have suggested that consuming caffeine might protect against the development of Parkinson’s. These more-recent studies set out to test this premise more directly in an animal model.

Both studies used mouse models of Parkinson’s that involved injecting mice with alpha-synuclein. This protein is a major component of Lewy bodies, irregular “clumps” in brain cells that are a hallmark of Parkinson’s pathology. Specifically, both research teams used a mutant form of the protein called A53T, which forms these clumps even more effectively than the wild-type protein.

In both studies, injection with A53T led to changes characteristic of Parkinson’s disease, such as impaired motor function and memory, as well as changes in brain physiology, like the development of the aforementioned Lewy bodies and loss of dendritic spines (parts of neurons involved in making connections in the brain).

However, when the mice were given caffeine in their drinking water, these effects were lessened. Both studies showed similarly beneficial results, though the exact parameters that were measured were different.

In the first study, researchers at Aarhus University, Denmark, report that mice given caffeine had less alpha-synuclein in their brains. Caffeine also caused a three–week delay in the onset of clasping, which is a behavior mice do with their hind limbs that is indicative of brain damage. Furthermore, caffeine-treated mice lived, on average, 40% longer than their counterparts who weren’t given caffeine.

In the second study, researchers at Wenzhou Medical University, China, reported that mice given caffeine had fewer memory problems and more dendritic spines than their untreated counterparts.

Both studies support the previous epidemiological evidence that caffeine can be protective for Parkinson’s disease, although there is the usual caveat that experiments in animal models are never a perfect replica of actual human disease.

It also is not clear why or how caffeine might have such protective effects, and further research will be needed to figure out just how caffeine might benefit Parkinson’s patients.

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Physical Activity, Coffee, Moderate Alcohol Consumption Protect Against Disease Progression, Study Reports

coffee, alcohol, lifestyle factors

Physical activity and participation in competitive sports, as well as coffee, caffeinated tea or moderate alcohol consumption before diagnosis, protect against worsening motor and cognitive function in Parkinson’s patients, according to a new population-based study.

In contrast, smoking and heavy alcohol consumption — or never consuming alcohol — correlated with higher risks of mortality and cognitive and motor decline.

The research, “The Association Between Lifestyle Factors and Parkinson’s Disease Progression and Mortality,” was published in the journal Movement Disorders.

Lifestyle factors such as coffee and moderate alcohol consumption, physical activity, and cigarette smoking have been linked with lower risk of Parkinson’s disease. Whether they affect disease progression remains undetermined, although small studies have shown that smoking and drinking coffee do not affect motor progression in Parkinson’s.

In turn, nonpaharmacologic approaches such as physical activity may benefit physical functioning, balance and gait, as well as protect against dementia.

Researchers at the UCLA Fielding School of Public Health and the David Geffen School of Medicine, in Los Angeles, California, assessed whether diverse lifestyle factors before a Parkinson’s diagnosis in adults affect motor progression, cognitive decline, and survival.

A total of 360 patients were enrolled within three years of diagnosis (average 2.1 years), as part of the population-based Parkinson’s Environment and Gene study in central California. The patients lived in one of three central California counties — Kern, Fresno or Tulare — and were followed from 2001 to 2016.

From the 252 patients not lost to follow-up (mean follow-up 5.3 years; 64 patients deceased, six were too ill, 17 withdrew, and 21 could not be contacted), 244 individuals — 139 men, mean age at diagnosis 66.9 years, mean duration of disease at baseline 2.1 years — provided data for analysis of disease progression.

The team also included 341 control participants from the same communities for analysis of mortality, who had been living in California for at least five years.

Telephone interviews were conducted to obtain self-reports of history of smoking, caffeinated coffee/tea or alcohol (beer, wine and liquor) consumption, overall physical activity level, and participation in competitive sports.

The participants were asked to report at what age they started and stopped drinking the beverages, as well as their average consumption per day during four age groups: 18-24, 25-44, 45-64, and 65 years or older.

Also, patients were asked about the average number of days per week and hours per day they participated in mild, moderate, or vigorous physical activity at the same age groups. Participation in competitive sports also was addressed, including basketball (20.6% of participants), baseball (18.1%), football (18.1%), track and field (12.5 %), and softball (8.3%).

Physical examinations were performed at each visit to assess motor function — Hoehn & Yahr (H&Y) stages — and cognition, with the Mini-Mental State Exam (MMSE). Cognitive decline was defined as a 4-point decrease from baseline MMSE examination.

In total, 209 patients (58%) and 67 controls (20%) died during follow-up. Fifty of the 244 patients (21%) assessed for progression experienced a 4-point or greater decline on the MMSE, while 77 (32%) progressed to H&Y stage 3 — transition from mild to moderate motor dysfunction, with loss of balance — or worse.

Coffee, caffeinated tea, moderate (below the median drinks per day), beer or liquor consumption, and participation in competitive sports were protective against mortality. In contrast, smoking and never drinking coffee or alcohol correlated with increased risk of mortality. Of note, the higher risk with smoking contrasts with prior studies showing protection against disease onset, the scientists noted.

In controls, alcohol and coffee consumption also were protective, while smoking conferred greater mortality risk.

The data further showed that engaging in competitive sports was associated with a history of head trauma in Parkinson’s patients, but not in controls. Head trauma also was linked with shorter time from diagnosis to death in this subset of patients.

Ever coffee consumption, participating in competitive sports and physical activity were protective against both motor function worsening and cognitive decline. Compared to moderate drinkers, patients who never drank liquor and those who drank more heavily were at greater risk for motor dysfunction. Also, never drinking and current cigarette smoking were associated with increased risk of cognitive decline.

Comparing patients who never drank coffee to those who have ever drank it, the findings also showed that never consuming coffee was associated with younger age at diagnosis (62.6 vs 67.6 years), longer disease duration at baseline (2.7 vs. 1.9 years) and less weekly alcohol consumption at some point (44% vs 69%).

“Although replication is needed,” researchers wrote, “our study suggests that multiple lifestyle factors potentially modify the rate of symptom progression.”

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Caffeine Plus Coffee Compound Linked to Serotonin Help Protect Brain from Toxic Damage, Mouse Study Says

coffee and its compounds

Two compounds found in coffee — caffeine and EHT, a fatty acid molecule derived from serotonin — work together to protect the brain from damage induced by alpha-synuclein, a study in mice reported.

The study, “Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson’s disease and DLB,” was published in PNAS.

Parkinson’s disease is characterized by alpha-synuclein aggregates. When this protein clumps, it gives rise to small fibrils that accumulate inside brain cells, producing small inclusions called Lewy bodies. These structures are highly toxic and often cause irreparable damage to affected nerve cells, slowly killing them.

Previous studies have shown that alpha-synuclein is abnormally hyperphosphorylated — a chemical modification in which a phosphate group is added to the protein — in the brain of patients with Parkinson’s. This is caused by the lack of activity of the protein phosphatase 2A (PP2A), an enzyme responsible for removing phosphate groups from alpha-synuclein.

Of note, alpha-synuclein phosphorylation is known to occur in Parkinson’s disease, and is thought to be a critical step in disease progression as it enhances alpha-synuclein’s toxicity —possibly by increasing the formation of alpha synuclein aggregates.

Interestingly, studies also report that Eicosanoyl-5-hydroxytryptamide or EHT — a fatty acid molecule found in coffee — promotes the activation of PP2A. In transgenic (or genetically engineered) mice, it was able to reverse the symptoms of phosphorylation to produce large quantities of alpha-synuclein.

The chemical serotonin, a neurotransmitter, is known to serve as a “feel-good” chemical in the brain, influencing a person’s sense of well-being and happiness.

“Considering epidemiologic and experimental evidence suggesting protective effects of CAF [caffeine] in PD [Parkinson’s disease], we sought, in the present study, to test whether there is synergy between EHT and caffeine in models of [alpha]-synucleinopathy,” the researchers wrote.  “[A]mong patients with early PD, the amount of CAF consumption does not impact the rate of progression of the disease, and decaffeinated coffee has been found to be protective in Drosophila models of PD, raising some question about the protective effect of only CAF among the numerous other compounds in coffee.”

Researchers treated alpha-synuclein transgenic mice (SynTg) — which overexpress alpha-synuclein in nerve cells — with either higher doses of caffeine and EHT separately, or with lower doses of both compounds for six months.

SynTg mice treated with caffeine and EHT had lesser accumulation of hyperphosphorylated alpha-synuclein in the brain, which was linked to higher levels of active PP2. These animals also  maintained neuron integrity and function, had lower brain inflammation, and performed better on behavioral tests.

Investigators found the same therapeutic benefits when they used the combined treatment in another mouse model of alpha-synucleinopathy, in which animals were injected with pre-formed fibrils of alpha-synuclein (alpha-Syn PFF).

In both animal models, however treatment with either caffeine or EHT alone failed to produce the same positive effects.

“These findings suggest that these two components of coffee have synergistic effects in protecting the brain against [alpha]-synuclein−mediated toxicity through maintenance of PP2A in an active state,” the researchers wrote.

“As we begin to unravel the polypharmacology of the micronutrients in commonly consumed botanical extracts such as coffee, it seems likely that it will be possible to optimize their composition to enhance efficacy so as to provide widely available, inexpensive, and effective therapeutics for the prevention and treatment of neurodegenerative diseases such as PD, DLB [dementia with Lewy bodies], PSP [progressive supranuclear palsy], and AD [Alzheimer’s disease],” they concluded.

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Certain Compounds in Coffee, But Not Caffeine, Seen to Prevent Protein Buildup Linked to Parkinson’s in Early Study

coffee consumption

Chemical compounds in coffee — especially phenylindanes that form during the roasting of coffee beans — appear to prevent the damaging aggregation of amyloid-beta and tau known to play key roles in Parkinson’s and Alzheimer’s disease, researchers report.

Caffeine, in contrast, had no effect on protein buildup in this early lab study, and researchers saw coffee consumption to offer no protection against alpha-synuclein aggregation.

The study, “Phenylindanes in Brewed Coffee Inhibit Amyloid-Beta and Tau Aggregation,” was published in Frontiers in Neuroscience.

Coffee consumption has been suggested to reduce the risk of developing diabetes, various cancers, and neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Despite the available evidence, however, it’s unclear what how exactly coffee can help to prevent age-related cognitive decline.

Past studies have reported that caffeine, the main bioactive compound of coffee, can reduce the risk of Parkinson’s both in men and in women who were not taking hormone replacement therapy. It has also been seen to reduce nerve cell death in the substantia nigra – the brain area most affected in Parkinson’s – in mouse models of the disease.

However, recent data also suggests that long-term consumption of caffeine may exacerbate anxiety-related behavioral and psychological symptoms in patients with dementia, counteracting its potential beneficial effects.

These contrasting findings highlight the need to identify those coffee components that may be neuroprotective.

Researchers led by Donald Weaver, MD, PhD, co-director of the Krembil Brain Institute, evaluated the potential of chemical components of coffee to inhibit the buildup of proteins that can drive neurodegenerative diseases like Alzheimer’s and Parkinson’s, in particular: amyloid-beta, tau, and alpha-synuclein.

The team started by examining three types of instant coffees — light roast, dark roast, and decaffeinated dark roast — in terms of their ability to prevent protein aggregates. They tested the instant coffees by adding them to one of these three proteins in an in vitro (laboratory dish) context.

“The effect of caffeine content would be assessed by comparing the activity of caffeinated and decaffeinated dark roast coffee extracts. Further, since it is known that different levels of roasting affect the composition of the coffee brew, comparison of light versus dark roast coffee extracts was also performed,” the researchers wrote.

Dark roast coffee showed the greatest inhibitory effect against tau protein buildup. Interestingly, the level of caffeine in each type of coffee had no impact on tau, amyloid-beta, and alpha-synuclein’s ability to aggregate.

“We were surprised to find that caffeine content did not influence aggregation inhibition, and thus performed a post-hoc analysis of pure caffeine,” the researchers said in the study. “No effect on fibril growth was observed relative to the vehicle control, consistent with the results for caffeinated versus decaffeinated coffee extracts.”

Further experiments found that all coffee extracts could prevent amyloid-beta and tau protein aggregation at 200 μg/mL concentration. Dark roast coffee (with or without caffeine) was seen as more potent in preventing the oligomerization — a chemical form that proteins can take — of amyloid-beta than the light roast extract.

All types of coffee as an instant mix, however, showed an ability to promote alpha-synuclein aggregation at amounts above 100 mg/mL.

To better understand these findings, the team then explored the activity of the six main chemical components of coffee — caffeine, chlorogenic acid, quinic acid, caffeic acid, quercetin, and phenylindane.

Researchers found that most of these compounds — with exception of caffeine and quinic acid for amyloid-beta, and caffeine and caffeic acid for tau — prevented protein aggregation.

Phenylindane was found to hold the strongest inhibitory activity, working as a dual-inhibitor to prevent the formation of amyloid-beta aggregates by 99% and those of tau tangles by 95.2%. Importantly, in later experiments, phenylindanes did not show “pro-aggregation behavior” toward alpha-synuclein, the study reported.

Phenylindanes are formed during the roasting of coffee beans and are found in higher concentrations in dark roast coffees, which have longer roasting times.

“It’s the first time anybody’s investigated how phenylindanes interact with the proteins that are responsible for Alzheimer’s and Parkinson’s,” Ross Mancini, a research fellow in medicinal chemistry at the Krembil institute and the study’s first author, said in a news release.  “The next step would be to investigate how beneficial these compounds are, and whether they have the ability to enter the bloodstream, or cross the blood-brain barrier.”

The team is now investigating if phenylindanes can reduce amyloid-beta, tau and alpha-synuclein loads in cell and animal models of Alzheimer’s and Parkinson’s disease.

Researchers caution that their findings are not recommendation for excessive coffee consumption.

“What this study does is take the epidemiological evidence and try to refine it and to demonstrate that there are indeed components within coffee that are beneficial to warding off cognitive decline,” Weaver said. “It’s interesting, but are we suggesting that coffee is a cure? Absolutely not.”

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