치매에 대한 이해 치매의 유형, 진행 및 관리 [치매] 이해하기

### 치매에 대한 이해 치매의 유형, 진행 및 관리
* 🧠 치매는 인지 기능과 일상 활동을 손상시키는 진행성 신경 퇴행성 질환으로, **알츠하이머병이 가장 흔한 하위 유형**으로 **전체 치매의 70%**를 차지합니다.
* 🔍 **혈관성 치매, 루이체 치매, 전두측두엽 치매 등 치매의 여러 하위 유형**에는 고유한 특징과 근본적인 원인이 있습니다.
* 🕰 치매는 **치매 전 단계(경도 인지 장애)**부터 시작하여 **초기, 중기, 말기**로 진행되며, 각 단계마다 뚜렷한 증상과 어려움이 있습니다.
* - **APOE 유전자 변이와 같은 유전적 요인**이 알츠하이머 위험에 영향을 미치며, **다운증후군은 조기 발병 알츠하이머의 중요한 위험 요인**입니다.
* 치매의 진단은 주로 **임상 병력, 인지 평가, 혈액 검사 및 영상 검사를 통한 가역적 원인 배제** 등을 바탕으로 이루어집니다.
* 💊 치매를 완치할 수 있는 치료제는 없지만 **콜린에스테라아제 억제제나 메만틴 같은 약물**은 증상을 관리하고 인지 기능 저하를 늦추는 데 도움이 될 수 있습니다.
* 🏋 규칙적인 운동 및 행동 전략과 같은 생활 습관 개입도 **질병 진행에 긍정적인 영향**을 미칠 수 있습니다.
* 💀 치매는 폐렴과 같은 합병증으로 인해 **1년 사망률이 30~40%**, **5년 사망률이 약 65%**에 달하는 등 사망률에 큰 영향을 미칩니다.

진행성 신경 퇴행성 질환인 치매는 알츠하이머, 혈관성 치매, 전두측두엽 치매 등 다양한 아형을 포괄하며 인지 기능 저하와 기능 장애를 유발합니다.

foreign [Music]. Dementia is an umbrella term that describes a progressive neurodegenerative disease characterized by cognitive decline, causing an impairment in daily functioning. Under this umbrella, we have multiple subtypes, including Alzheimer's, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Neurodegeneration means that cells in the nervous system stop working and eventually die. This happens naturally as we age, but in dementia, there are abnormal changes that increase how many cells are lost. This loss of neurons and their connections results in the symptoms described as cognitive decline, which is quite a general term. It means an impairment in one of memory, executive function, language, attention, or visuospatial functions like recognizing faces or environments. Since dementia is progressive, these can be seen to be getting worse over time. In the earliest stage, called the pre-dementia stage, there can be subtle symptoms such as anosmia, which is the loss of sense of smell. This can occur as far back as 10 years before the first clinical signs of

dementia. There can be mild cognitive impairment, but it does not impair daily functioning, which is a defining feature of dementia. Examples could be some difficulty in finding occasional words or some forgetfulness. Once the symptoms are profound enough to cause impairment in daily function, it is called early-stage dementia. Here, symptoms are apparent to other people, such as forgetting to take medication, misplacing objects, difficulty in accomplishing tasks around the house, managing finances, as well as planning and organizing. In the middle stage, people tend to lose the ability to acquire new information, particularly in Alzheimer's. It's also here that they begin to require assistance with personal care and hygiene, and there can be more behavioral disturbances like restlessness, aggression, and repetitiveness. They may also demonstrate a lack of insight into their condition, and problems with orientation also become more apparent. In the latest stages, people will believe that they are in a different time, commonly in an earlier time in their life. This is called time shifting, and patients may ask for people who are no longer alive.

the ability to speak may be lost regressing only to a few words. Depression and anxiety become more common in the later stages, and hallucinations also become more prominent. Restlessness is very common at this stage, and aggression may be more present as it is more difficult for patients to express their needs. Dangers like hot stoves may no longer be recognized, and faces or places also no longer recognized. There can also be physical difficulties; walking becomes more difficult, leading to more time in chairs or in a bed, which predisposes to venous thromboembolism. Nutrition is challenging as swallowing difficulties often develop, which can result in aspiration and ultimately pneumonia. The duration of the timeline varies but tends to be roughly two years in each stage. Once functionally impaired, the most common subtype of dementia is Alzheimer's disease, which makes up around 70 percent of cases worldwide. As with most subtypes, Alzheimer's is the result of accumulation of insoluble proteins in the brain. There are two in particular involved in Alzheimer's; the first is beta amyloid.

which forms extracellular plaques, also known as extracellular senile plaques. The second is hypophosphorylated Tau protein, which accumulates inside neurons to form neurofibrillary tangles. Beta amyloid comes from the breakdown of a normal transmembrane protein called amyloid precursor protein. It is cleaved by alpha, beta, and gamma secretes and is normally broken down. But if the beta secretes ACT first and is then followed by gamma secretes, this generates beta amyloid and leads to the formation of the plaques. These proteins lead to dysfunction and death of the neurons. They are found in normal brains; however, in Alzheimer's, there is a significantly higher quantity, and they're found in more particular locations, specifically the hippocampus, parietal, and temporal lobes. Although dementia symptoms can generally be similar, the subtypes can have slightly different presentations. Alzheimer's often presents with short-term memory loss and difficulty finding words. Visio spatial impairment is also fairly common; for example, getting lost and problems with insight, meaning they do not realize that they

have problems with their memory. Vascular dementia makes up around 15 percent of cases and generally involves disturbance in the blood supply to the brain, leading to ischemia and loss of cells. If the blood supply to the brain is interrupted, causing the neurons to die, this could be called a stroke. It is thought that in vascular dementia, there could be a series of small strokes, which alone are not evident, but as they increase in number, the symptoms then develop. This is known as multi-infarct dementia. Subcortical dementia is another common type of vascular dementia, in which the smaller penetrating vessels are affected, sometimes called small vessel disease. Because of the close linked to strokes, it's no surprise to have a stroke-related subtype of vascular dementia, with up to 30 percent of patients with ischemic strokes estimated to go on and develop vascular dementia. In the periods between events, there may be little to no decline, followed by sudden decline when new insults occur. This gives vascular dementia the characteristic stepwise progression. Risk factors include smoking, diabetes

atrial fibrillation, dyslipidemia, hypertension, and age. With the risk doubling every five years in vascular dementia, impairments in planning, organizing, and judgment are noticeable early on. Lewy Body dementia is seen in around 10 percent of cases. Louis bodies are spherical deposits with surrounding fibers found in the cytoplasm of neurons. The center of the deposit is formed from Alpha-synuclein and ubiquitin aggregates. Lewy bodies are also a primary brain abnormality in Parkinson's disease dementia. Lewy Body dementia has core symptoms such as fluctuating cognition, visual hallucinations, and parkinsonian symptoms like bradykinesia, which is the slowing of movements, cogwheel rigidity, a predisposition to falls, and autonomic disturbances like orthostatic hypotension, incontinence, and constipation. It also has suggestive symptoms like REM sleep disturbance or antipsychotic sensitivity. One or more core with one or more suggestive symptoms is enough for a probable

diagnosis. While having only one or more suggestive gives a possible diagnosis, the second most common dementia in people under the age of 65 is frontal temporal dementia, just behind early Alzheimer's, with the mean age of onset being 53. Experts believe that there are two main disease processes involving transactive DNA binding protein (TDP-43) and the microtubule-associated Tau protein. Behavioral variant type is the most common subtype, characterized by personality changes and behavioral changes like disinhibition and social withdrawal occurring early on in the process. Spherical collections of Tau fibrils can be found in the cytoplasm, called pick bodies, which is why frontal temporal dementia was in the past called Pick's disease. Semantic variant manifests with language difficulties, including difficulties in finding words, as well as impairments in comprehension. This variant features a form of fluent aphasia. Non-fluent primary Progressive Aphasia features labored, hesitant speech rather than fluency, and these two are under the category of primary Progressive aphasia. Increasing age is generally the largest

risk factor. At age 65, there is a two percent prevalence, while at 85, it is as high as 40 percent. Genetics also play a role. For example, a family history of a first-degree relative with Alzheimer's increases the risk by between 10 and 30 percent. Early-onset dementia is defined as dementia affecting people under the age of 65, which makes up around five percent of all cases. The trisomy 21 or Down syndrome is a significant risk factor for developing early-onset Alzheimer's. There are three chromosomes instead of two, which could mean more amyloid precursor protein and therefore more beta-amyloid being produced. In Alzheimer's, there can be autosomal dominant transmission with near-complete penetrance. This is the case in around five percent of all cases and in most cases of early-onset Alzheimer's. For the early-onset variant, the three genes in particular are amyloid precursor protein on chromosome 21, presenilin 1 and 2 on chromosomes 14 and 1. For later-onset Alzheimer's, APO

lipoprotein E genes play a larger role. It is a regulator of lipid metabolism and can interact with beta-amyloid. The E4 variant is thought to produce a 50% risk of developing Alzheimer's, while having two alleles is thought to produce a 90% risk. Dementia in general is more common in women, but this may be because women tend to live longer than men. Cognitive Reserve is another factor. It is the extent of neuronal loss that can be tolerated before function is impaired. People who are socially isolated, left education early, or have low job complexity typically have a lower reserve and are therefore more likely to develop dementia. We've also already mentioned risk factors for vascular dementia. The only conclusive diagnostic test for Alzheimer's is a brain biopsy and histological confirmation, which is rarely done in living people. Some imaging techniques like positron emission tomography or PET scans are being developed that can detect these histological findings non-invasively. Therefore, the clinical history alongside a largely normal neurological exam is most commonly how dementia is suspected.

a mental state examination is done to evaluate cognition. Examples being the mini-mental state exam and the Montreal cognitive assessment. Blood tests are usually normal. However, there are some reversible causes of cognitive impairment that can be detected, such as vitamin B12 or folate deficiency, hypothyroidism, electrolyte disturbance like hypocalcemia, and even infective causes like Lyme's disease and neurosyphilis. CT imaging can help to rule out other causes of cognitive impairment and may also reveal cerebral atrophy, meaning a shrinking in the brain volume. Although this is suggestive, it is not specific for dementia. Genetic tests are not routinely done, and this is mostly reserved for rare familial forms. No cure currently exists for dementia. The one-year mortality is 30 to 40 percent, while the five-year mortality is around 65 percent. The most common cause of death is pneumonia, which may be because swallowing problems can predispose to aspiration and subsequently pneumonia. Some medications are used to reduce the symptoms, such as cholinesterase.

Inhibitors, which prevent the enzyme cholinesterase from breaking down acetylcholine, a neurotransmitter involved in cognition and memory. Examples include Donepezil, Galantamine, and Rivastigmine. NMDA receptor antagonists like Memantine are also used. These two classes have been found to slow the cognitive decline, but the effect on overall survival is not yet conclusive. In vascular dementia, a key part of management is addressing identified risk factors, which may help in slowing the progression. Behavioral and environmental approaches are encouraged. For example, maintaining a familiar environment, monitoring personal comfort, and redirecting attention. People with dementia are also prone to developing anxiety, depression, or even psychosis, and it is also important to treat these symptoms as well. Regular aerobic exercise has been found to slow down the progression of Alzheimer's disease.

Understanding Dementia (Alzheimer's & Vascular & Frontotemporal & Lewy Body Dementia)

Rhesus Medicine

치매에 대한 이해 증상 및 진행

치매는 인지 기능 저하와 일상 기능 장애를 일으키는 진행성 신경 퇴행성 질환입니다.

치매에는 알츠하이머병, 혈관성 치매, 루이소체 치매와 같은 하위 유형이 포함됩니다.

이 질환은 미묘한 증상이 나타나는 치매 전 단계에서 심각한 인지 기능 저하, 행동 장애, 신체적 장애가 나타나는 후기 단계로 진행됩니다.

알츠하이머병은 전 세계적으로 약 70%를 차지하는 가장 흔한 하위 유형으로, 베타 아밀로이드를 비롯한 불용성 단백질이 축적되는 것이 특징입니다.

알츠하이머병에서 베타 아밀로이드와 타우 단백질의 역할

베타 아밀로이드와 저인산화 타우 단백질은 알츠하이머병의 주범으로, 플라크와 신경섬유 엉킴을 형성합니다.

이러한 단백질은 주로 해마와 측두엽에 영향을 미쳐 신경세포 기능 장애와 사망을 유발합니다.

알츠하이머병은 단기 기억 상실, 언어 장애, 시공간 장애가 특징입니다.

15%의 비율을 차지하는 혈관성 치매는 주로 뇌로 가는 혈액 공급이 중단되어 발생하며, 작은 뇌졸중으로 인해 증상이 단계적으로 진행되는 경우가 많습니다.

혈관성 치매의 위험 요인으로는 흡연과 당뇨병이 있습니다.

혈관성 치매의 위험 요인으로는 심방세동, 이상지질혈증, 고혈압, 나이가 있으며, 5년마다 위험이 두 배로 증가합니다.

루이체 치매는 10%에서 발견되며 루이체, 알파-시누클레인, 유비퀴틴 응집체가 특징이며 인지력 저하, 시각 환각 등의 핵심 증상이 나타납니다.

65세 미만에서 두 번째로 흔한 치매인 전두측두엽 치매는 행동 변이형, 의미 변이형, 비언어성 원발성 진행성 실어증 등의 하위 유형이 있으며, 53세에 발병하고 TDP-43 및 타우 단백질과 관련이 있습니다.

알츠하이머 유병률은 나이가 들수록, 특히 65세 이후부터 증가하며 유전적 요인이 강합니다.

65세 미만에서 발병하는 조기 치매는 다운증후군 및 특정 유전자 돌연변이와 관련이 있습니다.

APO 지단백질 E 유전자는 나중에 발병하는 알츠하이머와 관련이 있으며, E4 변종은 위험이 높음니다.

인지 예비력, 혈관성 치매, 인구통계학적 요인도 위험에 영향을 미칩니다.

알츠하이머 진단은 여전히 어렵고 임상 병력과 신경학적 검사에 의존하는 경우가 많지만, 새로운 영상 기술이 비침습적 진단에 대한 가능성을 보여주고 있습니다.

미니 정신 상태 검사 및 몬트리올 인지 평가와 같은 정신 상태 검사와 비타민 결핍 및 감염과 같은 가역적 원인에 대한 혈액 검사를 통해 인지력을 평가합니다.

CT 촬영은 다른 원인을 배제하고 뇌 위축을 밝혀내는 데 도움이 될 수 있지만 유전자 검사는 드뭅니다.

현재 치매를 완치할 수 있는 치료법은 없으며 1년 사망률은 30~40%에 달합니다.

콜린에스테라아제 억제제나 메만틴과 같은 약물을 사용하여 증상을 완화하고, 위험 요인을 해결하고 행동적 접근법을 사용하는 것이 치매 관리의 핵심입니다.

규칙적인 유산소 운동은 알츠하이머병의 진행을 늦추는 것으로 밝혀졌습니다.