Neurocognitive Disorders PDF

Neurocognitive Disorders - Chap 17 What Are The Causes of Cognitive Impairment? Acquired causes - Can be related to illness, disease state, and/or other biomedical factors, eg., traumatic brain injury, drugs & alcohol, chronic stress Degenerative causes -...

Neurocognitive Disorders - Chap 17 What Are The Causes of Cognitive Impairment? Acquired causes - Can be related to illness, disease state, and/or other biomedical factors, eg., traumatic brain injury, drugs & alcohol, chronic stress Degenerative causes - Can be related to diseases that have no cure, that will continue to progress Neurocognitive Disorders in the DSM-5-TR Delirium - rapidly developing disturbance of attention or awareness not better explained by preexisting or evolving neurocognitive disorder Mild Neurocognitive Disorder - modest decline in one or more cognitive domains; cognitive deficits do not interfere with ADLs (activities of daily living), though the patient may need greater effort or compensatory strategies to maintain ADLs Major Neurocognitive Disorder - major decline in one or more cognitive domains; cognitive deficits interfere with ADLs What is Delirium? Delirium = a neurocognitive disorder characterized by a disturbance in awareness and attention not better explained by preexisting or evolving neurocognitive disorder Timeframe: develops over a short period of time and may fluctuate in severity over the course of a day Symptoms: - Clouded state of consciousness - Extreme trouble focusing attention - Disturbances in sleep/wake cycle - Fragmented thinking - Speech is rambling and incoherent - Disorientation  - Perceptual disturbances - Memory impairments - Mood swings - Secondary to underlying medical condition Detection of delirium is important but often missed - untreated , further cognitive decline and mortality may occur Beyond treating the underlying medical conditions, the most common treatment is atypical antipsychotic medication Prevalence - Low in the community overall, but increases with age - 10-30% in older individuals presenting at emergency depts - 14-25% in individuals upon hospital admission - 15-56% of older individuals postoperatively - 70-87% of older people in intensive care - Up to 60% of individuals in nursing homes/post acute care settings - Up to 83% of all individuals at the end of life Characteristics of Normal Aging Intelligence remains intact Normal performance mental status examinations (MSE) Occasional complaints of memory loss Memory loss can be recognized at any age Failure to appreciate wearing ripped jeans? Disorders of Cognition Cognitive “mishaps” are a common and quite normal feature of stress or aging As people move through middle age, these memory difficulties and lapses of attention increase, and they may occur regularly by age 60 or 70 Sometimes, however, people experience memory and other cognitive changes that are far more extensive and problematic Neurocognitive Disorders Categories listed as Neurocogntive Disorders in DSM-5-TR: - Delirium Rapidly developing disturbance of attention or awareness not better explained by preexisting or evolving neurocognitive disorder - Mild neurocognitive disorder (“mild neurocognitive impairment”) Modest decline in one or more cognitive domains; cognitive deficits do not interfere with ADLs, though the patient may need greater effort or compensatory strategies to maintain ADLs - Major neurocognitive disorder (“dementia”) Major decline in one or more cognitive domains; cognitive deficits interfere with ADLs Differential Diagnosis Process of making a diagnostic decision, in which clinician rules out other diagnoses in favor of one diagnosis over another Mild Neurocognitive Disorder Minor cognitive decline from previous levels in one or more domains based on both of the following - Concerns of the patient, a close other, or a clinician - Neurocognitive performance below appropriate norms (i.e., between the 3rd and 16th percentile) on formal testing, or equivalent clinical evaluation The cognitive deficits do not interfere with independence, even though greater effort, compensatory strategies, or accommodations many be required to maintain independence The cognitive deficits do not occur exclusively in the context of a delirium and are not due to another psychological disorder Major Neurocognitive Disorder Evidence of significant cognitive decline from previous levels in one or more domains based on both of the following:  - Concerns of patient, a close other, or a clinician - Neurocognitive performance below the 3rd percentile on formal testing, or equivalent clinical evaluation Impact: symptoms must exceed cultural and contextual normal. Symptoms interfere with independence Rule out: symptoms do not occur exclusively in the context of delirium 6 Cognitive Domains in Which Deficits may Occur for Mild and Major Neurocognitive Disorders Complex attention: focusing/sustaining attention Executive functions: planning and decision making; working memory Learning & memory: learning new skills & remembering them Language: speaking comprehension Perceptual-motor: hand-eye coordination, etc… Social-cognition: recognitioning emotions in others Dementia Is an umbrella term that describes many neurocognitive disorders - Alzheimer’s disease - Vascular dementia - Lewy body disease - Frontotemporal dementia - Other dementias (dementias associated with Parkinson's disease, Huntington's disease, etc…) Mild Neurocognitive Disorder due to… Alzheimer’s disease Frontotemporal lobar degeneration Lewy body disease Vascular disease Traumatic brain injury  Substance/medication use HIV infection Prion disease Parkinson’s disease Huntington’s disease Another medical condition Multiple etiologies Unspecified Major Neurocognitive Disorder due to… (more significant impairment) Alzheimer’s disease Frontotemporal lobar degeneration Lewy body disease Vascular disease (multi infarct dementia) Traumatic brain injury Substance/medication use HIV infection Prion disease Parkinson’s disease Huntington’s disease Another medical condition Multiple etiologies Unspecified Alzheimer’s Disease Described by Alois Alzheimer in 1906 Irreversible brain tissue deterioration - Death usually occurs within 12 years Usually begins with… - Difficulty remembering recent events - Learning new material  - Irritability As disease progresses… - Language problems intensify, including word-finding - Disorientation 1. Time, place, and identity confusion - Agitation - Depression Brain Changes in Alzheimer’s Disease Neuritic Plaques - β-amyloid protein deposits - Primarily found in frontal cortex Neurofibrillary tangles - Protein filaments composed of tau in axons of neurons - Primarily found in hippocampus Measured using PET scans Plaques most dense in frontal cortex; tangles most dense in hippocampus Loss of synapses for acetylcholinergic (Ach) and glutaminergic neurons - As neurons die, atrophy of cerebral and entorhinal cortices and hippocampus - Enlargement of ventricles Alzheimer’s Related Dementia Amyloid Plaques Neurofibrillary Tangles Current Research Amyloid scans to detect Alzheimer’s disease Recap:  Amyloid plaques are formed from amyloid precursor proteins, APP, a protein that resides in our brains. APP can form fragments which clump together with debris from dying neurons to form amyloid plaque A protein called TAU normally benefits the cell. It’s a structural component that forms microtubules, transporting molecules from one part of the cell to another. Abnormal or unhealthy TAU leads to collapse of the microtubules, which twist; these are neurofibrillary tangles Causal Factors About Alzheimer’s Disease Related Dementia Early-onset ADRD - prior to age 65  - Relatively rare (5% of all cases) - Associated with 3 causal genes (APP, PS1, PS2) Late onset ADRD - At or after age 65 - Common (95% of all cases) - Associated with a vulnerability allele (form) of APOE nameled APOE-e4 Etiology of Alzheimer’s Disease: Genetic Factors Polymorphism of a gene on chromosome 19 Apolipoprotein ε4 or ApoE-4 allele - Increases production of amyloid precursors Before the development of symptoms, people with two ε4 alleles show: - Overproduction of beta-amyloid plaques - Loss of neurons in the hippocampus - Low glucose metabolism in several regions of the cerebral cortex Alzheimer’s Disease Heritability 79% ApoE4 allele: gene on chromosome 19 - Having 1 E4 allele increases risk by 20% - Having two E4 alleles increases risk substantially more Related to overproduction of beta-amyloid plaques, loss of neurons in the hippocampus, and low glucose metabolism in cerebral cortex Etiology of Alzheimer’s Disease: Risk Factors Greater risk: - Smoking, being single, low social support, and depression related to greater risk of developing Alzheimer’s Lower risk - Cognitive factors (e.g.: solving crossword puzzles, reading the newspaper daily) Etiology of Alzheimer’s Disease: Lifestyle Factors Greater risk: - Social isolation, insomnia Lower risk - Fish consumption, mediterranean diet, education - Exercise (predicts less decline in cognitive functioning and decreased risk of developing Alzheimer’s - Engagement in cognitive activities “Use it or lose it” Frequent cognitive activity is related to a 46% decrease in risk Intellectual activity protects against the expression of underlying neurobiological disease Cognitive reserve: some people may be able to compensate for the disease by using alternative brain networks or cognitive strategies Prevention and Treatment of Dementia Medications - No drug reverses Alzheimer’s disease - Some drugs produce slightly less decline 1. Cholinesterase inhibitors (drugs that prevent the breakdown of acetylcholine) 2. Donepezil (Aricept) 3. Galantamine (Reminyl) Vitamin E, statins, and nonsteroidal anti-inflammatory drugs have failed to find support Preventive work focuses on processes involved in the creation of amyloid from its precursor protein Antidepressants for depression Antipsychotic medication for agitation Drugs Used to Treat Alzheimer’s Dementia Two Main types: a. Cholinesterase – inhibitors - Work by preventing the breakdown of acetylcholine, stimulate the nicotinic receptors to release more Ach in the brain - Drug: Execlon (rivastigmine) – prescribed to treat sx’s of middle to moderate A - Drug: Razadyne (galantamine) – prescribed to treat sx’s of mild to moderate AD. side effects: nausea, vomiting, diarrhea, weight loss b. NMDA antagonists - Work by blocking the toxic effects associated with excess glutamate and regulate glutamatergic activation - Drug: namenda (memantine) – prescribed to treat sx’s of moderate to severe AD. side effects: dizziness, headache, constipation, confusion New Drug used to treat alzheimer’s dementia (as of June 7, 2021) Different from the other two types of drugs This drug is a human monoclonal antibody that preferentially binds to aggregated (clumped) beta amyloid to reduce the # of amyloid plaques This drug is a targeted at the underlying pathophysiology of AD (works by removing beta-amyloid) Drug: Aduhelm (aducanumab) – prescribed to treat sx’s of mild AD to improve clinical outcome. Side effects: increased risk of strokes, brain bleeds Why are we *hopeful* about drugs like Aduhelm? - First drug to slow disease progression Why was Aduhelm Developed? Beta amyloid peptide → Aβ protein → accumulates in brain as amyloid plaques Neuritic plaques disrupt communication between neurons and may also activate immune system cells, trigger in inflammatory response in brain The Beta-amyloid hypothesis  - Aβ-related toxicity is the main cause of the synaptic dysfunction and subsequent neurodegeneration which forms the basis of Alzheimer dementia progression So by directly targeting the beta amyloid peptide, Aduhelm trying to reduce the Aβ plaques in the brain Newer Drugs Developed to Treat MCI Due to Alzheimer’s Disease These drugs are antibodies that preferentially bind to aggregated (clumped) beta amyloid to reduce the # of amyloid plaques These drugs are targeted at the underlying pathophysiology of AD Work by removing beta-amyloid - Drug – Becanemab (Leqembi) - Drug – Donamemab (Kisuna) Prescribed to treat sx’s of Mild Cognitive Impairment to slow the progression of the disease to AD Side effects: increased risk of strokes, brian bleeds, and ARIA (amyloid-related imaging abnormalities) Treatment of Dementia Psychological treatments - Supportive psychotherapy for family and patient - Education about disease and care - Cognitive interventions when disease is in early stages - Labeling drawers, appliances - Calendars, clocks, and strategically placed notes - Exercise has been associated with cognitive benefits - Music appears to reduce agitation and disruptive behavior Vascular Neurocognitive Disorder A neurocognitive disorder in which the blood vessels in the brain become damaged or blocked, resulting in decreased flow oxygen to those parts of the brain  There may be sudden cognitive dysfunction in specific functions depending on the size of the brain affected Frontotemporal Neurocognitive Disorder Loss of neurons in frontal and temporal lobes - Memory not severely disrupted Impairment of executive functions - Planning - Problem solving - Goal-directed behavior Difficulty recognizing and regulating emotion - Much more profound impact than Alzheimer’s Caused by multiple genetic pathways - Pick’s disease 1. Associated with tau protein 2. Behavioral variant FTD (bvFTD) - Diagnosed with 3 or more of the following symptoms are present: 1. Behavioral disinhibition 2. Lack of sympathy and empathy 3. Obsessive-compulsive or repetitive behaviors 4. Change in food preference or placing inappropriate objects in mouth - High levels of tau proteins Parkinson’s Disease 3rd most common Characterized by tremors or rigid movements Primarily caused by loss of dopamine neurons About 75% eventually show signs of cognitive impairment Lewy Body (DLB) Disease  Lewy bodies are microscopic round, abnormal protein deposits that develop in the brain and damage the neurons Symptoms similar to Parkinson’s and Alzheimer’s diseases - Shuffling gait - Loss of memory Symptoms differ in that DLB patients have: - Fluctuating cognitive symptoms - Prominent visual hallucinations - Intense dreams involving movement and vocalizing - REM sleep behavior disorder Symptoms are hard to distinguish from Parkinson’s and Alzheimer’s disease Symptoms are more likely to include: - Promentine visual hallucinations - Fluctuating cognitive symptoms - Sensitivity to physical side effects of antipsychotic medications - Intense dreams involving movement and vocalizing Huntington’s Disease Rare degenerative disorders of CNS Chronic, progressive chorea Patients usually develop dementia Death occurs 10-20 years post symptom onset Associated with having too much dopamine Chronic Traumatic Encephalopathy (CTE) Discovered build-up of tau protein in brain A form of dementia that is different from Alzheimer’s Dementia and associated with different protein abnormalities in the brain upon autopsy People who experience repeated head injuries (mild, moderate, or severe) eg. boxers, football players, and combat veterans, are at higher risk for CTE  Characterized by an accumulation of p-tau in cortical regions, microgliosis, esp in the lateral and frontal cortex Dramatic atrophy of the frontal, medial temporal, and anterior thalamic regions Psychiatric sxs include: aggression, mood (depressive) symptoms, cognitive deficits, and memory loss. Increased suicide risk as disorder progresses