Major Neurocognitive Disorders

Overview

Definition

• The term “major neurocognitive disorders (NCDs)” describes a group of disorders characterized by progressive cognitive impairments.
• Also known as dementia
• To be classified as an NCD, there must be a clear decline from previous levels of functioning and cognitive baseline in a person.

Epidemiology

• About 20% of people above 65 years of age meet the criteria for major NCD. 
• About 70% of these patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease (most common cause of major NCD).
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency increases with age to a rate of ≥ 20% for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship over the age of 85 years.
• Serious economic and social impact, as these individuals often require a caregiver for the rest of their lives

Etiology

Most common:

• Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease
• Vascular dementia
• Lewy body dementia
• Parkinson’s disease dementia
• Frontotemporal dementia Frontotemporal dementia Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of tau protein inclusions. Ftld includes three clinical syndromes: frontotemporal dementia, semantic dementia, and primary progressive nonfluent aphasia. Amyotrophic Lateral Sclerosis
• Metabolic abnormalities ( hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, uremia Uremia A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of renal insufficiency. Most uremic toxins are end products of protein or nitrogen catabolism, such as urea or creatinine. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms. Acute Kidney Injury) 
• Nutritional deficiencies (vitamin B₁₂/ folate deficiency Folate deficiency A nutritional condition produced by a deficiency of folic acid in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B12 deficiency do not occur. Megaloblastic Anemia)
• Dementia secondary to depression 

Less common:

• Creutzfeldt-Jakob disease Creutzfeldt-Jakob Disease A rare transmissible encephalopathy most prevalent between the ages of 50 and 70 years. Affected individuals may present with sleep disturbances, personality changes, ataxia; aphasia, visual loss, weakness, muscle atrophy, myoclonus, progressive dementia, and death within one year of disease onset. A familial form exhibiting autosomal dominant inheritance and a new variant cjd (potentially associated with bovine spongiform encephalopathy) have been described. Pathological features include prominent cerebellar and cerebral cortical spongiform degeneration and the presence of prions. Transmissible Spongiform Encephalopathies
• Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome
• Huntington disease Huntington disease Huntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant mode of inheritance and poor prognosis. It is caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene (HTT). The most common clinical presentation in adulthood is a movement disorder known as chorea: abrupt, involuntary movements of the face, trunk, and limbs. Huntington Disease
• HIV HIV Anti-HIV Drugs dementia 

Pathophysiology

Pathophysiology of the most common causes of the major NCDs are shortly described below.

Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease

• Accounts for 60%–70% of dementia cases
• Characterized by:
  • Loss of neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology in cortex and subcortex → atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation of primarily the temporal and parietal lobe Parietal lobe Upper central part of the cerebral hemisphere. It is located posterior to central sulcus, anterior to the occipital lobe, and superior to the temporal lobes. Cerebral Cortex: Anatomy
  • Accumulation of beta-amyloid plaques, tau protein, and potentially Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease inside neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology

Vascular dementia

• Primary cause of vascular dementia is cerebral vascular disease.
• Risk factors: same as those for cardiovascular disease 
• Reduction in cerebral perfusion Cerebral Perfusion Syncope → disruption of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification connectivity, cerebral atrophy Cerebral Atrophy Subdural Hemorrhage

Dementia with Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease

• Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease are thought to be responsible for impaired mental functions related to thinking, movement, behavior, and mood in dementia with Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease.
  • Abnormal aggregation Aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Coagulation Studies of protein (α-synuclein) within nerve cells is the chief component of Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease. 
  • Found abundantly in brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification cells of people suffering from dementia with Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease and Parkinson’s disease dementia (less commonly in Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease)
• Presence of Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease alters the level of neurotransmitters and neuromodulators in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification, principally dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS. 

Parkinson’s disease dementia

• Loss of pigmented dopaminergic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology in the substantia nigra Substantia nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis. Basal Ganglia: Anatomy ( pars compacta Pars compacta A region in the substantia nigra located dorsal to the pars reticulata. Parkinson’s Disease) 
• Presence of Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease
• Leads to destruction of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification cells and depletion of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS (hormone that controls muscle coordination Coordination Cerebellar Disorders) in the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy

Frontotemporal dementia Frontotemporal dementia Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of tau protein inclusions. Ftld includes three clinical syndromes: frontotemporal dementia, semantic dementia, and primary progressive nonfluent aphasia. Amyotrophic Lateral Sclerosis

• Different types of dementia affecting the frontal Frontal The bone that forms the frontal aspect of the skull. Its flat part forms the forehead, articulating inferiorly with the nasal bone and the cheek bone on each side of the face. Skull: Anatomy and temporal lobes
• Damage to neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology → shrinkage of the frontal Frontal The bone that forms the frontal aspect of the skull. Its flat part forms the forehead, articulating inferiorly with the nasal bone and the cheek bone on each side of the face. Skull: Anatomy and temporal lobes of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
• Assumed to have stronger genetic component than other types of dementia
• Mostly affecting people aged 50–60, but can also manifest much earlier or later 

Clinical Presentation

General features

Significant decline in cognition in the following domains: 

• Attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment
• Executive function
• Learning/ memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment
• Language
• Perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment
• Social interaction

Symptoms are not explained by other medical, psychiatric conditions (depression, delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium).

Specific subgroups of dementia

Diagnosis

History and exam

• Determine onset and development of symptoms.
• Involve collateral information from caregiver, if possible.
• Mental status exam:
  • Cognition must be tested separately using screening Screening Preoperative Care tests.
    • Examples: Mini-Cog, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MoCA)
    • No one test is superior clinically to another.
  • It is recommended to repeat the screening Screening Preoperative Care tests to detect progression of the cognitive decline.
  • Be wary of symptoms of depression, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, or paranoia, which can present concurrently with cognitive impairment!

Further workup tests

The following are mostly used to differentiate or rule out treatable medical or neurologic conditions that cause a decline in cognition: 

• Basic lab tests:
  • CBC
  • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes 
  • Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH) 
  • Vitamin B₁₂ and folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 levels
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children
• Ancillary labs:
  • HIV HIV Anti-HIV Drugs antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (→ HIV-associated dementia HIV-associated dementia A neurologic condition associated with the acquired immunodeficiency syndrome and characterized by impaired concentration and memory, slowness of hand movements, ataxia, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. AIDS-defining Conditions)
  • Rapid plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products reagin (→ syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis)
  • Serum copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements, ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease levels (→ Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease)
  • CSF analysis CSF analysis Meningitis:
    • Beta-amyloid 
    • Total tau
    • Phosphorylated-tau (p-tau)
• Imaging of the head Imaging of the head Today, CT and MRI, especially the latter, are the preferred imaging methods for the study of the cranial vault and its contents. In conditions where emergent management is decided on the basis of presentation and imaging, CT has the advantage of rapid scan time and wider availability. Imaging of the Head and Brain:
  • Mostly to rule out tumors and vascular disease 
  • CT
  • MRI
  • PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging 
• Neuropsychological tests:
  • Assess ability to speak and work with numbers, memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment, and problem-solving skills.
  • Can distinguish symptoms from various etiologies of major NCDs

Management

General approach

• Identify and treat reversible causes of major NCD early.
• For nonreversible cases, management techniques focus on preserving quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life by prevention as well as treatment of symptoms. 
• To date, there are no treatments to completely cure major NCDs. 

Prevention

• Control of blood pressure, cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels, and blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance level
• Regular Regular Insulin physical activity and healthy diet
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation 
• Cognitive exercises 

Pharmacotherapy

• Treatments for Alzheimer disease Alzheimer disease As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Alzheimer Disease dementia:
  • Acetylcholinesterase inhibitors ( donepezil Donepezil An indan and piperidine derivative that acts as a selective and reversible inhibitor of acetylcholinesterase. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate dementia in alzheimer disease. Cholinomimetic Drugs, galantamine, rivastigmine Rivastigmine A carbamate-derived reversible cholinesterase inhibitor that is selective for the central nervous system and is used for the treatment of dementia in alzheimer disease and parkinson disease. Cholinomimetic Drugs)
  • Increase the amount of available neurotransmitters and thus transmission of signals.
  • Long-term use modestly stabilizes cognitive decline for 6–12 months longer than no treatment. 
  • Side effects:
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
    • Muscle cramps Cramps Ion Channel Myopathy
  • Also has shown benefits for managing major NCDs such as dementia with Lewy bodies Lewy bodies Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of lewy bodies is the histological marker of the degenerative changes in lewy body disease and parkinson disease but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex. Parkinson’s Disease and Parkinson’s disease dimentia
• Drugs to avoid:
  • Antipsychotics ( haloperidol Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics and quetiapine Quetiapine A dibenzothiazepine and antipsychotic agent that targets the serotonin 5-HT2 receptor; histamine h1 receptor, adrenergic alpha1 and alpha2 receptors, as well as the dopamine d1 receptor and dopamine D2 receptor. It is used in the treatment of schizophrenia; bipolar disorder and depressive disorder. Second-Generation Antipsychotics):
    • Lead to altered consciousness, confusion, and hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
    • Use only in acute, severe cases of agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus 
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines: increase fall risk 

Caregiver support

• Educating and providing support for caregivers is an essential part of the treatment plan. 
• Long-term outcome of those with major NCDs has been shown to be dependent on the wellness of the caregivers.

Complications and Prognosis

Complications

• Frequent hospitalizations due to:
  • Frequent falls, fractures 
  • Behavioral disturbances with increased agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus and personality changes 
  • Inability to take care of oneself 
• Death:
  • Often caused by acute illnesses due to increased frailty
  • 2 leading causes: pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia and ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease 

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas for major NCDs is very poor.
• 5-year mortality Mortality All deaths reported in a given population. Measures of Health Status: estimated at 60% 
• Earlier onset or family history Family History Adult Health Maintenance of dementia is linked with more rapid course of the disease.

Differential Diagnosis

• Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium: an acute change in mental status characterized by impairments in attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment, cognition, and arousal. Similar to dementia, delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium is highly prevalent among the elderly population. While delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium is always of acute onset, dementia progresses gradually, with worsening of the symptoms. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with dementia are consciously alert and pay attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment to the current happenings, whereas patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium have altered consciousness levels. 
• Depression: characterized by persistent low mood and loss of interest in association with somatic symptoms Somatic symptoms Major Depressive Disorder for a duration of at least 2 weeks. Depression in elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can manifest as “pseudodementia,” where the patient presents with cognitive decline much like that seen in NCDs. Those with pseudodementia will have more prominent depressive mood symptoms, often a prior history of depression, and better insight Insight Psychiatric Assessment into their condition than those with dementia. 
• Normal aging: minor memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment problems may occur as part of normal aging. The associated minor cognitive decline is called benign Benign Fibroadenoma senescent forgetfulness. The amount of memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment impairment is difficult to quantify in normal aging; however, it is clearly distinguished from major NCDs due to the patient having intact activities of daily living as well as no issues with orientation Orientation Awareness of oneself in relation to time, place and person. Psychiatric Assessment.