Genetics: Renewed Importance Of Apoe Gba Variants And Potential Role Of Lysosomal Dysfunction
Given the overlap in clinical symptoms and neuropathologic features among PDD, AD, and DLB, genetic association studies represent a powerful tool to identify areas of potential divergence in molecular mechanism and to highlight shared genetic risk factors that may represent common neurodegenerative pathways. A recent multicenter study of neuropathologically confirmed DLB cases reported 3 genetic loci with significant associations with the DLB phenotype, corresponding to the genes for APOE , Syn , and SCARB2 , a lysosomal protein previously linked to PD. Another study found that the APOE4 allele associated with DLB regardless of the presence of A pathology, suggesting that APOE may have an A-independent effect on DLB and PDD pathogenesis. The importance of APOE was further underscored by the finding that the APOE4 variant was associated with poorer cognitive performance in a study of more than 1,000 patients with PD across multiple centers. Interestingly, the authors noted that the MAPT H1 haplotype, while associated with overall PD risk, did not predict cognitive performance in this dataset. Other recent studies have been mixed with respect to association of the MAPT H1 haplotype and rate of cognitive decline in PD.,
The Era Of Digital Cognitive Testing
The development of digital cognitive testing and the evolution of self-completed computerized assessments and wearable devices to assess cognitive functioning in daily life, provides an exciting opportunity to both improve clinical management and to obtain more sensitive outcome measures for clinical trials and will likely become a standard procedure in the future, given further technological improvements and increased access to the internet and digital devices. To reach this point, psychometric requirements , documentation and technical problems, as well as their relation to traditional tests, need to be well known.
How Is Parkinsons Disease Diagnosed
A person doesnt need to have all the signs and symptoms of Parkinsons disease to be diagnosed with it.
In general, people have a combination of the motor symptoms and the non-motor symptoms, says Dr. Nwabuobi. Some people have more non-motor symptoms than motor and vice versa, but in order to have a diagnosis of Parkinsons, you definitely need the motor symptoms. Were looking for specific things , including a rest tremor, bradykinesia, rigidity, and poor balance.
According to the Parkinsons Foundation, a person needs to have two of the four main motor symptoms of Parkinsons over a period of time to be diagnosed with the disease.
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What Are The Different Types Of Memory Loss Diseases
Alzheimers disease, Parkinsons disease, Huntingtons disease, and multi-infarct dementia are among the most common types of memory loss diseases. Memory loss, also sometimes referred to as dementia, is most commonly associated with aging, but it can actually affect any individual at any age. This is particularly true in individuals who have developed specific diseases. Modern medicine may help slow the decline of memory loss attributed to these conditions, but there is no way to cure any of them.
Memory loss may be acute or chronic. Acute cases are typically attributed to a sudden physical or emotional trauma. Chronic memory loss, however, is mostly due to one of several progressive diseases and is mostly irreversible.
As people age, minor memory loss is considered normal, and deficits in memory are not necessarily caused by any known diseases. The aging process is, however, often accompanied by the threat of certain diseases known to impair cognitive functioning.
Dementia And Parkinsons Disease
In this 2-hour webinar geriatrician Naaz Parmar provides an understanding of dementia as a disease, the different subtypes of dementia, and how they affect a person with concurrent PD. This webinar also gives an overview of treatment options with lifestyle changes and medications. Coping strategies for a person with dementia and their loved ones, will also be discussed.
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Classification Issues And Prodromal Stages
The proposal that dementia prior to or simultaneous with motor symptoms can be included in the diagnostic criteria for PD, has reopened the long-standing debate on whether PDD and DLB should be considered the same disease,,,. A deeper understanding of the pathophysiological processes underlying these two synucleinopathies, such as the relative contribution of -amyloid and tau pathology in cortex and striatum, the extent of cortical Lewy pathology and -synuclein load in the hippocampus, the severity of neuronal loss in the substantia nigra, and cholinergic cell loss, is required to better understand the relationship between PD and DLB.
Although some risk factors for cognitive impairment have been identified,,, further research is needed to better identify any early evidence of cognitive impairment in genetic at-risk populations and in individuals with clinical features of prodromal PD to provide opportunities for prevention strategies and early precision therapy interventions.
Coping With Dietary Problems
Many people with Parkinsons experience various eating and dietary problems, such as constipation, chewing and swallowing difficulties, and upset stomach. The following tips can help you minimize the symptoms.
If you suffer from constipation Drink lots of water and eat fiber-rich foods, including beans, brown rice, whole grains, and fruit.
If you have trouble chewing or swallowing food Cut foods into smaller portions to avoid choking and to encourage digestion, and remain upright for 30 minutes after eating.
If youre struggling with fatigueLimit the amount of sugar youre eating. Also avoid alcohol and caffeine, especially before bed, as they can reduce the quality of your sleep.
If you take levodopa Dont eat meat or other protein-rich foods for at least 30-60 minutes after taking levodopa, as protein blocks your bodys ability to absorb the medication.
If your medication gives you an upset stomach Take your medication with a full glass of water and a small non-protein based snack, such as a piece of toast or fruit.
Some Parkinsons disease medications need to be taken promptly at specified times before or after eating, so it can also help to establish a regular routine for meal and medication times.
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Asceneurons Innovation In Pdd And Dlb
Several symptomatic treatments addressing motoric disturbances in PD are currently available. In contrast, there is a very high unmet medical need for novel symptomatic medications to mitigate the cognitive decline in Parkinsons disease dementia patients, since available options have limited efficacy and considerable side effects. As the disease progresses, balancing the benefits of medications with their side effects becomes challenging for caregivers.
Asceneuron has generated small molecules of novel chemical classes that have the potential to deliver novel, well-tolerated and efficacious drugs to treat learning and memory deficits in dementia. Our positive allosteric modulators of the M1 muscarinic acetylcholine receptor have the potential to bring the first approved treatment for PDD to patients and a new class of molecules for the treatment of dementia in general. M1 PAMs induce a change in the shape of the receptor, enhancing binding to the neurotransmitter acetylcholine. As a result, receptor activity is potentiated so that it can still fulfill its signaling functions, critical for cognition, even in situations where acetylcholine levels are reduced as observed in Parkinsons disease dementia and other dementia in general.
Given the high unmet medical need in PDD, a symptomatic treatment for one of the more debilitating facets of PD would bring significant benefit to PD patients and their caregivers.
Other Reasons For Cognitive Symptoms
Besides PD, there are other important causes of cognitive dysfunction to keep in mind. Medical illnesses such as thyroid disease or vitamin B12 deficiency can cause cognitive symptoms. Urinary tract infections or pneumonia can acutely cause confusion or hallucinations. In these settings, the cognitive symptoms are generally reversible after the infection or medical condition is treated. One should be aware that some medications for pain or bladder problems may cause sedation/sleepiness or confusion, and, thereby, impair cognitive function.
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Can A Stroke Cause Parkinsons Disease
A stroke can cause some symptoms of Parkinsons disease, but not Parkinsons disease itself. This condition is called Parkinsonism. Parkinsonism is associated with many of the same movement problems of Parkinsons disease, such as tremors and stiffness. However, it usually does not worsen over time as Parkinsons disease does. If a stroke causes brain damage in the area of the brain that is associated with Parkinsons disease, then Parkinsonism can occur.
Clinical Value Of The Present Findings
Our PD participants had problems in WM updating that were unrelated to their other cognitive difficulties, such as prolonged response latencies, difficulties in maintaining attention and inhibiting irrelevant information, and episodic memory deficits. As compared to other WM subdomains, updating was the only subdomain that clearly discriminated PD patients from healthy controls even when no other problems were considered. Altogether, these findings suggest that the WM subdomain of updating should receive particular attention when surveying onset cognitive deficits in PD patients. However, further test development is needed to utilize this knowledge in practice, as standardized, readily available measures of WM updating are lacking.
What Are The Symptoms
Symptoms of PD vary from person to person, as does the rate of progression. A person who has Parkinsons may experience some of these more common hallmark symptoms:
- Bradykinesia slowness of movement, impaired dexterity, decreased blinking, drooling, expressionless face.
- Tremor at rest involuntary shaking that decreases with purposeful movement. Typically starts on one side of the body, usually the hand.
- Rigidity stiffness caused by involuntary increase in muscle tone.
- Postural instability sense of imbalance. Patients often compensate by lowering their center of gravity, which results in a stooped posture.
Other symptoms that may or may not occur:
Freezing or being stuck in place Shuffling gait or dragging of one foot Stooped posture Cognitive impairment
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Managing Cognitive Impairments In Parkinsons
After a thorough evaluation to rule out other causes of cognitive impairment, patients with PD may be treated with medication, occupational therapy, and/or speech therapy. The medications used to treat cognitive impairments in people with PD are based on treatments used for Alzheimers disease. Occupational therapy can help a person with PD by providing adaptive strategies for daily activities. Speech therapy can help with language functions, as well as information processing. 3,4
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How Is A Diagnosis Made
Because other conditions and medications mimic the symptoms of PD, getting an accurate diagnosis from a physician is important. No single test can confirm a diagnosis of PD, because the symptoms vary from person to person. A thorough history and physical exam should be enough for a diagnosis to be made. Other conditions that have Parkinsons-like symptoms include Parkinsons plus, essential tremor, progressive supranuclear palsy, multi-system atrophy, dystonia, and normal pressure hydrocephalus.
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Background Characteristics And Group Comparisons For Single Measures
The groups were comparable on all demographic characteristics, as well as on motivation and alertness evaluations throughout the test sessions . The age of the PD group ranged from 45 to 72 years and they had an average education of 14.8 years . The mean age at disease onset had been 59.5 years , while the average disease duration had been 5.6 years . The age of the control group ranged from 50 to 73 years and they had an average education of 14.2 years .
There were some differences between the groups in cognitive performance, global cognitive abilities, self-reported everyday cognition, and self-reported affective symptoms . As shown in Table 2, the PD patients performed significantly worse than the healthy controls on SRT , CPT , and the Wordlist recall task . Sentence recall was the only non-WM task that systematically correlated with the WM tasks within the PD group .
Table 2. Group differences for computerized tasks between the PD patients and the healthy controls.
The PD patients exhibited also general cognitive impairment , and reported more everyday cognitive difficulties as well as depressive symptoms as compared to the controls. The PD patients did not, however, differ from the controls on the other global cognitive ability measure or on the self-reported apathy rating .
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Does Parkinsons Disease Cause Memory Loss
My mother was recently diagnosed with Parkinson’s and is becoming more and more forgetful. Is this a symptom of the disease?
Dr. Janis Miyasaki responds:
As many as 70 percent of Parkinson’s patients will ultimately end up developing dementiausually in the later stages of the disease.
Even in the early stages of the disease, tests show some patients starting to have subtle changes in thinking. These patients may not be able to access information as efficiently as they once did. They can have trouble doing two things at once.
One problem is that the medications we give Parkinson’s patients to help with motor problems can lead to worsening memory, confusion, hallucinations and delusions.
The good news is that the drugs used to treat Alzheimer’s seem to be more effective in patients with Parkinson’s . But these medications also can worsen a patient’s motor symptoms. Some notice they are slower and stiffer when taking these drugs. Some have increased .
So, there’s a trade-off. If a patient is reporting problems with memory and thinking and is having some hallucinations, I will try reducing the dosage of some of the less effective Parkinson’s drugs. And I will try them on the lowest doses of an Alzheimer’s medication.
The memory problems you mention are a sign that you’ll need to become more involved in your mother’s care and life. And you probably should be attending her doctor’s visits.
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What Are Parkinsons Disease Dementia And Lewy Body Dementia
Parkinsons disease is a progressive, degenerative neurological movement disorder that affects approximately 7 million people worldwide. It is the second most common neurodegenerative disorder after Alzheimer’s disease.
Up to 80% of Parkinsons disease patients will develop Parkinsons disease dementia that is characterized by a progressive loss of memory and decline in intellectual abilities.
About 15% of Parkinsons disease diagnoses include so-called Parkinsons plus syndromes. One of these syndromes is Lewy body dementia , also known as dementia with Lewy bodies , a form of progressive dementia accounting for 20% of dementias in people over the age of 65.
Depression May Be An Early Symptom Of Parkinsons
Depression is one of the most common, and most disabling, non-motor symptoms of Parkinsons disease. As many as 50 per cent of people with Parkinsons experience the symptoms of clinical depression at some stage of the disease. Some people experience depression up to a decade or more before experiencing any motor symptoms of Parkinsons.
Clinical depression and anxiety are underdiagnosed symptoms of Parkinsons. Researchers believe that depression and anxiety in Parkinsons disease may be due to chemical and physical changes in the area of the brain that affect mood as well as movement. These changes are caused by the disease itself.
Here are some suggestions to help identify depression in Parkinsons:
- Mention changes in mood to your physician if they do not ask you about these conditions.
- Complete our Geriatric Depression Scale-15 to record your feelings so you can discuss symptoms with your doctor. Download the answer key and compare your responses.
- delusions and impulse control disorders
Associations Between Cognitive Deficits And Psychiatric Symptoms
Neither everyday cognition nor psychiatric symptoms were correlated with WM performance in the PD group. These findings support the existence of subjective cognitive decline in PD , suggesting that objectively measured cognitive performance, subjectively experienced cognitive problems, and affective symptoms arise from distinct underlying factors. This is the case in WM as well. Lack of correlation between subjective cognitive complaints and task performance has also been observed in some previous studies with other cognitive measures . Our study further indicates that both everyday cognitive difficulties and affective symptoms are linked to PD symptoms, indicating that the various types of difficulties in daily living could have a common origin that perhaps relates to psychiatric well-being. Cognitive difficulties directly related to PD and those associated with a decline in global cognitive abilities could, in turn, have different underlying mechanisms. As noted above, our findings suggest a direct link between PD and WM updating, while more widespread WM deficits may occur in parallel with global cognitive decline.
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What Is Parkinson Disease
Parkinson disease is a movement disorder. It can cause the muscles to tighten and become rigid This makes it hard to walk and do other daily activities. People with Parkinsons disease also have tremors and may develop cognitive problems, including memory loss and dementia.
Parkinson disease is most common in people who are older than 50. The average age at which it occurs is 60. But some younger people may also get Parkinson disease. When it affects someone younger than age 50, it’s called early-onset Parkinson disease. You may be more likely to get early-onset Parkinson disease if someone in your family has it. The older you are, the greater your risk of developing Parkinson disease. It’s also much more common in men than in women.
Parkinson disease is a chronic and progressive disease. It doesn’t go away and continues to get worse over time.
Mild Memory And Cognitive Problems
Mild memory loss and thinking problems are known as mild cognitive impairment, or MCI. Many people experience some form of thinking or memory problems at some point in life, perhaps due to factors such as grief or stress. But when people experience greater difficulties with memory, language, thinking or judgment than might be expected at their age, they may have MCI.
The terms memory problems and ‘memory loss’ can be misleading because far more than just memory may be affected. If you have mild cognitive problems, you may experience:
- Slowed thought processes. You may find it hard to follow a number of steps to complete a task or have problems multi-tasking
- Difficulties with planning, problem-solving or making decisions
- Difficulties following and taking part in conversations
- Difficulty finding the right word
- Poor concentration
- Lack of motivation
- Short-term memory loss difficulty remembering names or the sequence of recent events
- Problems with judging distances or direction. Describing how to get from one place to another may become hard.
Visual hallucinations or delusions may accompany cognitive problems in some people. Sometimes these are drug induced or they may be related to Lewy body dementia so you should let your doctor know if you experience these symptoms.
People with cognitive difficulties may be unaware of the problems they are experiencing, and friends and family may notice first.
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