Major Neurocognitive Disorder HY 2024-02 PDF

HY: Major neurocognitive disorder Gonzalez MD START Major Neurocognitive Disorder Key points (1) Dementia according to the DSM-5 is now called Major Neurocognitive Disorder. However, due to the common use of the term dementia in society and medical literature, it will...

HY: Major neurocognitive disorder Gonzalez MD START Major Neurocognitive Disorder Key points (1) Dementia according to the DSM-5 is now called Major Neurocognitive Disorder. However, due to the common use of the term dementia in society and medical literature, it will be referred to as both Dementia and Major Neurocognitive Disorder. Major neurocognitive disorder can a ect younger individuals and does not always imply Alzheimer disease as the etiology. Major neurocognitive disorder is characterized by BEHAVIORAL CHANGES and a significant decline in at least one of the domains of cognition which is not better explained by a nondegenerative, psychiatry disorders or systemic conditions. The decline represents a change from a patient's prior level of cognitive ability, is persistent and progressive, there must also be a decline in the patient's ability to function and perform everyday tasks. The everyday function is o en evaluated in terms of the ability to perform IADLs (Instrumental Activities of Daily Living), such as managing finances or medications, or, if more severe, ADLs (Activities of Daily Living), such as grooming or feeding oneself. Individuals o en do not have insight into their deficits. Currently, no cure exists. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Major Neurocognitive Disorder Key points (2) The diagnostic process requires a history taken from the patient and a reliable informant, as well as objective measures of impairment through a neuropsychiatric and neuropsychological assessment. Definitive classification of dementia is based on the underlying neuropathology (biopsy). However, dementias can be sorted into syndromic categories on the basis of distinct clinical features. The accuracy of clinicopathological diagnoses is improved by the use of imaging, biofluid and genetic biomarkers. In addition, simple treatable causes of cognitive impairment, such as hypothyroidism, vitamin B12 deficiency, infection or medication-induced problems, must be sought and ruled out. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Epidemiology Around 40% of those aged 65 or over thought to be living with dementia do not have a diagnosis. Currently, 47 million people in the world have dementia, and the number is expected to increase to 131 million by 2050. The individual lifetime cost to care for an individual with dementia was nearly $200,000 more than an individual without dementia. The age cut-o for early versus late onset of dementia is arbitrarily set at 65 years, which is historically the typical age for retirement. 50% of people with Downʼs syndrome will develop dementia. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ https://dementiastatistics.or Alzheimer´s Disease International https://www.alzint.org  Pathogenesis (1) Dementia is a complex process involving an interplay between specific molecular pathways (deposit of abnormally folded proteins) causing: Loss of synaptic connections Cell death Gliosis Inflammation Disruption of functional networks underlying cognition, personality, behaviour and sensorimotor functions, eventually attacking an individualʼs autonomy. Ageing is the most robust risk factor for dementia (90% of dementias presenting a er the age of 65 years). Accumulation of abnormally folded proteins lies at the heart of dementia neuropathology: Alzheimer disease: disruption of the memory system, language, visuospatial and behavioural executive domains Frontotemporal lobar degeneration: aggregates of tau, TDP‑43 or FUS, can give rise to frontotemporal dementia syndromes The most definitive classification is based on the accumulation of abnormal protein aggregates in neurons and glia. Mild Cognitive Impairment: the Manchester consensus These aggregates perturb the neural networks subserving cognitive, behavioural and sensorimotor Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 functions. doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ The functional domains a ected serve as footprints that the clinician can trace back with various levels of Alzheimer´s Disease International certainty to the underlying neuropathology. https://www.alzint.org Subtypes of dementia Dementia is a term used to cover a group of diseases that cause decline in cognitive function. Alzheimerʼs disease is the most common and well-known disease that causes dementia, accounting for 60-70% of all dementia cases. It is characterised by amyloid plaques and neurofibrillary tangles in the brain, resulting in brain cell death. Vascular dementia is caused by reduced blood supply to the brain, o en as a result of a stroke and can have a sudden onset. Lewy body dementia is named for the build-up of abnormal proteins in the brain called Lewy bodies. Frontotemporal dementia specifically a ects the frontal and temporal lobes of the brain resulting in changes in behaviour, and a deterioration in language and social skills. Mixed dementia is characterised by the presence of more than one type of dementia, which can be more challenging to diagnose and manage. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Key Points (2) Dementia UAG 1 PrImer NATURE REVIEWS | DISeASe PRIMeRS | Article citation ID: ( 2020) 6:68  Key Points (2) Dementia UAG 1 PrImer NATURE REVIEWS | DISeASe PRIMeRS | Article citation ID: ( 2020) 6:68 Alzheimer´s Disease Neuropathology: Alzheimer AD pathology is a DUAL PROTEINOPATHY defined by the coexistence of: Aβ42 fibrils -- (extracellular aggregates) — and, to a lesser extent... Aβ40 fibrils — that form neuritic Aβ plaques (amyloid), and... P-tau/NFTs -- (intracellular aggregates) Hyperphosphorylated tau (neurofibrillary tangles). The gradual spread of NFTs begins subcortically in noradrenergic projections and correlates with progression of cognitive deficits The amyloid deposition, o en di use at the time of symptom presentation Amyloid deposition typically starts in the large pyramidal neurons in layer II of the cortex, the CA1 region of the hippocampus, corticopetal cholinergic neurons in the basal forebrain, and noradrenergic neurons in the locus coeruleus There is a synergy between tau and amyloid in the progression: 1. Neuronal loss results is noradrenergic deficiency, and ensuing symptoms such as attentional deficits. 2. Involvement of cholinergic neurons in the nucleus basalis of Meynert results in an important cholinergic deficit, and loss of serotonergic neurons in the dorsal raphe nucleus contribute to psychiatric changes. 3. The cortical regions displaying accumulation of abnormal tau include the temporal lobes, the hippocampal formation and the neocortex. 4. The abnormally phosphorylated tau no longer binds to microtubules, leading to misfolding and aggregation, forming insoluble NFTs (causing Alzheimer´s Society neuronal premature apoptosis, which results in loss of grey matter) https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Alzheimer´s Disease: Genetic mutations The late-onset form of the disease is defined as AD with onset at age 65 years or older and accounts for the majority of AD cases. A genetic risk factor for late-onset AD was identified as the type ε4 allele of the gene for apolipoprotein E (APOE), located on chromosome 19 has essential roles in cholesterol homeostasis and triglyceride metabolism also this mutation can a ect the Amyloid depuration Compared with non-carriers, individuals with one APOE ε4 allele have a three- to four-fold risk of developing AD, while those with two APOE ε4 alleles have a 5–18 times greater risk of developing the disease. Early-onset, generally before the age of 65, is a rare familial form of AD that accounts for approximately < 5% of all cases Down-syndrome associated AD (DSAD) Autosomal dominant AD (ADAD) To date, 106 mutations on three separate genes are associated with the early-onset form of AD: the amyloid precursor protein (APP) gene on chromosome 21 the presenilin 1 (PSEN1) gene on chromosome 14, the presenilin 2 (PSEN2) gene on chromosome 1. Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Alzheimer´s Disease: Diagnostic approach Currently, the diagnosis of AD is largely one of exclusion: Clinical history Psychiatric history Neurological examination Cognitive testing Neuroimaging All of these serve to exclude other common neurodegenerative disorders Others: 1. MRI to evaluate pattern of atrophy, concomitant vascular disease, and nondegenerative lesions (mimics) 2. Molecular biomarkers (cerebrospinal fluid (CSF: Total Tau, Phosphorylated Tau, Amyloid) or PET) for early-onset AD, atypical clinical features or possibility of frontotemporal lobar degeneration; 3. 18F-FDG–PET if patient is amyloid-negative according to CSF or PET studies and MRI is inconclusive. 4. Genetic testing: PSEN1, PSEN2 if familial cause Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Alzheimer´s Disease (Clinical approach - algorythm) STEP #1: CLINICAL ASSESSMENT A diagnosis of AD dementia requires insidious onset and gradual progression of deficits in two cognitive domains, one being memory. Incorporating in vivo biomarkers as well as genetics. STEP #2: POTENTIAL GENETIC ETIOLOGY Sporadic AD is predominantly a late-onset dementia, presenting a er the sixth to seventh decade of life, Familial AD usually presents earlier (10-20% cases) with a clear family history showing a Mendelian inheritance pattern (PSEN1, PSEN2 and APP genes). Sporadic LOAD is the prototypical AD syndrome. STEP #3: STRATIFICATION (STAGES) Amnestic di iculties with formation of new episodic memories, is frequently the first clinical presentation of typical — or amnestic — AD. Decreased semantic fluency can also be noted on neuropsychological testing. Overall, typical AD is defined by prominent early episodic memory deficits, reflecting neurodegeneration of the limbic system and the medial temporal lobe. Additional deficits such as acalculia and visuospatial dysfunction localize to parietal lobes. Noradrenergic and cholinergic deficits can be prominent, a ecting mood and frontal lobe functions, with diminished attention and concentration. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org UAG  Alzheimer´s disease: structural neuroimaging Patterns of brain atrophy: Atrophy is first noted in the medial temporal lobes, and gradually spreads to involve the broader temporoparietal and posterior cingulate cortices. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Alzheimer´s Disease (Clinical approach) Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Vascular Dementia Frontotemporal Dementia Lewy Body Dementia  Vascular Dementia Cardiovascular disease a ecting vessels of various calibres can cause infarcts and haemorrhages, as well as chronic progressive white matter disease, including demyelination, axonal injury, astrocytosis and oedema, with infiltration of macrophages and activation of microglia. In contrast with other neurodegenerative diseases,vascular dementia is not characterized neuropathologically by accumulation of abnormal proteins. Nonetheless, vascular disease tends to be progressive and degenerative, with cognitive impairment following clinical stroke or resulting from subclinical vascular brain injury. Chronic cerebral Small vessel disease: the most insidious subtype, shows the strongest association with cognitive impairment. It is associated with blood–brain barrier (BBB) compromise, resulting in leakage of fluid and macromolecules, and chronic white matter disease (cortical and subcortical microinfarcts, lacunar strokes, a chronic state of cerebral hypoperfusion, hippocampal atrophy, and sclerosis). The histopathological substrate includes lipohyalinization of vessels, formation of microatheromas within vessels, fibroid necrosis, enlarged Virchow–Robin spaces, and astrocytic gliosis. There may be a potential risk of having synergistic interactions between SVD and AD pathology. Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Frontotemporal Dementia Frontotemporal lobar degeneration (FTLD) a ects the pregenual anterior cingulate cortex Tau Tau is encoded by the microtubule-associated protein tau gene. Alternative splicing of MAPT mRNA leads to production of six tau isoforms with di erential expression across the brain. Tau binds to and stabilizes microtubules, which are important for cellular morphology and function. The normally phosphorylated tau becomes aberrantly hyperphosphorylated, dissociates from microtubules, and forms aggregates within neurons and glia. Frontotemporal lobar degeneration a ects the pregenual anterior cingulate cortex Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Classical Lewy body. These neuronal inclusions are cytoplasmic, brightly eosinophilic and they Lewy body dementia are surrounded by a clear halo. Lewy body dementia Pathology: It is characterized by the presence of intracellular α-synuclein aggregates (Lewy bodies) that cause dysfunction of cerebral neuronal networks. Typically manifest symptomatically between the ages of 60 and 90 years. Pesticide exposure, TBI and a history of melanoma are possible risk factors for DLB. The defining clinical features of DLB localize to cortical and subcortical structures, with the ensuing characteristic combination of cognitive and motor dysfunction The core diagnostic features of DLB include fluctuating cognition, recurrent visual hallucinations, and parkinsonism. The fluctuations in mental status, may be due to profound Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. cholinergic deficits in addition to neocortical Lewy body pathology Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Key Points (2) Dementia UAG 1 PrImer NATURE REVIEWS | DISeASe PRIMeRS | Article citation ID: ( 2020) 6:68 Dementia Timeline Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  Understanding & respecting the person with dementia Someone with dementia, whose mental abilities are declining, will feel vulnerable and in need of reassurance and support. A person with dementia is still an adult It is important that everyone continues to treat the person as an adult and with courtesy, and respect however advanced their dementia. Never talk over the head of a person with dementia or across them as though they are not there. Do not talk about the person with dementia in front of them unless they are included in the conversation. Look for the meaning behind what they may be trying to communicate even if it seems not to make sense. The person with dementia needs to feel respected and valued for who they are now, as well as for who they were in the past. Be flexible and tolerant UAG 2020 American Medical Association. All rights reserved Caregiver burden prevention 1. The emotional burden is very important as caregivers are more likely to be depressed, they tend to increase the use of psychotropic medicines and visit doctors more o en 2. They do not sleep well and feel exhausted. 3. The constant anxiety is a particularly aggravating factor Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Tips to tackle family tension around Alzheimer´s Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Understanding Dementia Medical-Legal Implications A person with Dementia could be at risk to be manipulated in a case of undue influence. The victim of a scam, might be vulnerable if they have Alzheimerʼs. Proving the presence or absence of Dementia and other cognitive defects might shi the pivot of a case or direction towards settlement or trial. Legal matters rest on decision-making. Whether the case is probate litigation or fraud, a decision-makerʼs competency and lucidity can be at issue. Informed Decisions: If a person with Dementia is making a will or trust, selling real estate or a business, or making gi s of money, art or other tangible items, the potential legal consequences are troubling. Assessing if Dementia is or is not present is a job for a physician qualified to assess neurocognitive disorders. Everyone, including doctors, are alerted by signs and symptoms that raise the possibility Dementia is present. Mild Cognitive Impairment: the Manchester consensus Alzheimer´s Society Published by Oxford University Press on behalf of the British Geriatrics Society. https://www.alzheimers.org.uk/ Age and Ageing 2021; 50: 72–80 Alzheimer´s Disease International doi: 10.1093/ageing/afaa228 https://www.alzint.org Prevention Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org Interventions There is no cure for dementia, but a lot can be done to support both people living with the illness and those who care for them. People with dementia can take steps to maintain their quality of life and promote their well-being by: being physically active taking part in activities and social interactions that stimulate the brain and maintain daily function. In addition, some medications can help manage dementia symptoms: Cholinesterase inhibitors like donepezil are used to treat Alzheimer disease. Selective serotonin reuptake inhibitors (SSRIs) can help with severe symptoms of depression in people living with dementia if lifestyle and social changes donʼt work, but these should not be the first option. Mild Cognitive Impairment: the Manchester consensus Alzheimer´s Society Published by Oxford University Press on behalf of the British Geriatrics Society. https://www.alzheimers.org.uk/ Age and Ageing 2021; 50: 72–80 Alzheimer´s Disease International doi: 10.1093/ageing/afaa228 https://www.alzint.org Major Neurocognitive Disorder. Key factors | risk and protective factors for dementia and Alzheimer disease across the lifespan. Some factors can di erentially a ect the risk of dementia and Alzheimer disease in an individual depending on the time of exposure within the life course. For example, hypertension, obesity and dyslipidaemia increase dementia risk when a person is exposed during midlife. By contrast, other factors such diet a ect risk across the lifespan. CAIDE, Cardiovascular Risk Factors, Aging and Dementia Social withdrawal exacerbates negative symptoms Mild Cognitive Impairment: the Manchester consensus Published by Oxford University Press on behalf of the British Geriatrics Society. Age and Ageing 2021; 50: 72–80 doi: 10.1093/ageing/afaa228 Alzheimer´s Society https://www.alzheimers.org.uk/ Alzheimer´s Disease International https://www.alzint.org  111222333 [email protected] Lorem Ipsum dolor 00, 2ºA 00000 Consecuteur (Amet) Any questions? [email protected]