Alzheimer Disease

Overview

Definition

Alzheimer disease is a progressive neurodegenerative disease that causes 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 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 and a decline in cognition, 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 social skills.

Epidemiology

• Leading cause of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders in adults > 65 years
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: women > men
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency increases exponentially after age 65. 
• 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 of Alzheimer disease after age 70 in the United States: 9.7%
• Familial Alzheimer disease called “early-onset” Alzheimer disease:
  • Rare (< 1% of cases)
  • Caused by genetic mutations Genetic Mutations Carcinogenesis
  • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance

Etiology

Although the cause of Alzheimer disease is unknown, several genetic defects and risk factors have been identified.

• Genetic factors: 
  • Amyloid precursor protein gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics:
    • Located on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21
    • Associated with approximately 1% of all early-onset Alzheimer disease and 0.1% of total Alzheimer disease cases
    • Age at onset of Alzheimer disease in individuals with this mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations is 45–66 years.
  • Presenilin-1 (PSEN1) mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations:
    • Located on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 14 
    • Linked to 50% of all familial Alzheimer disease cases
    • Age at onset: 28–62 years
  • Presenilin-2 (PSEN2) mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations:
    • Located on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 1 
    • Causes the rarest form of familial Alzheimer disease
    • Age at onset: 40–85 years
  • Apolipoprotein E gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (APOE ε4) mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations:
    • Located on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 19 
    • May increase Alzheimer disease risk by impairing beta-amyloid clearance 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
    • Age at onset is later than those listed above (> 60 years).
• Other risk factors: 
  • Age
  • Familial history of Alzheimer disease
  • Head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep deprivation
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Dyslipidemia
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension 
  • Peripheral atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis

Pathophysiology

The pathogenesis of Alzheimer disease is unclear; however, there is an increase in beta-amyloid peptides and 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 the tau protein.

• Pathways likely involved in Alzheimer disease:
  • Mutations in the genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure PSEN1 or PSEN2 may increase the production of amyloid or neurotoxic forms of beta-amyloid found outside 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.
  • Tau ( aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS in microtubule assembly and stabilization): hyperphosphorylation →  aggregates → abnormal helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) form of tau  → found inside neurofibrillary tangles
• Gross pathologic changes:
  • Cortical 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 with widening cerebral sulci
  • Compensatory ventricular enlargement 
• Microscopic pathologic changes found in the hippocampus:
  • Neurofibrillary tangles = bundles of filaments in the cytoplasm 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
    • Paired helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) filaments that contain hyperphosphorylated tau
    • Severity of Alzheimer disease directly correlates to the number of neurofibrillary tangles. 
  • Beta-amyloid “neuritic” plaques = focal, spherical collections of silver-staining neuritic processes
  • Amyloid angiopathy → granulovacuolar degeneration
• Low acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS → decrease in cognitive ability
• Autopsy studies in people > 85 years show pathologic findings of Alzheimer disease in ⅓ of individuals with no clinical diagnosis of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders before death.
  • More than half of brains from cases of Alzheimer disease show “mixed pathology” or 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 changes of ≥ 1 other causes of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders.
  • Concomitant cerebrovascular disease is common.
  • Lewy body disease is also seen.

Clinical Presentation

Interviewing family members is essential to obtain a history of cognitive and behavioral changes.

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

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 the most common early symptom of Alzheimer disease.

• Described as anterograde long-term episodic amnesia
• Insidious onset with slow gradual progression 
• In earlier stages of presentation: episodic 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 is affected = 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 of events occurring at a time and place
• In later stages 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:
  • Procedural learning and remote 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 
  • Semantic 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 = 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 for facts, vocabulary, and concepts
  • Immediate recall 

Impaired executive function and judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment

• Subtle to prominent impairment occurs in early Alzheimer disease.
• Ability to complete tasks declines
• Reduced insight Insight Psychiatric Assessment into deficits (anosognosia) ↑ over time 
• Associated with behavioral changes

Impairment in cognitive domains

• Develop and progress insidiously
• Visuospatial impairments: seen relatively early in the disease
• Language deficits and primary progressive aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke: manifest later

Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology function impairment

• Apraxia Apraxia A group of cognitive disorders characterized by the inability to perform previously learned skills that cannot be attributed to deficits of motor or sensory function. The two major subtypes of this condition are ideomotor and ideational apraxia, which refers to loss of the ability to mentally formulate the processes involved with performing an action. For example, dressing apraxia may result from an inability to mentally formulate the act of placing clothes on the body. Apraxias are generally associated with lesions of the dominant parietal lobe and supramarginal gyrus. Cranial Nerve Palsies = difficulty performing purposeful movements
  • Usually occurs after deficits in 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 language are apparent
  • Initially presents with difficulty performing complex, multistep activities
  • Later → difficulty with dressing, using utensils, and other self-care tasks 
• Shuffling gait Shuffling Gait Normal Pressure Hydrocephalus with generalized muscle rigidity Muscle rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Motor Neuron Lesions
• Slowness and awkwardness of movement

Behavioral and psychological symptoms

• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbances
• Apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome/social disengagement
• Irritability
• 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, aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder, wandering, and psychosis: difficult for family members
• Delusions in later stages: common themes of theft, infidelity, or misidentification

Other signs and symptoms

• Focal, nonmotor seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures with impaired awareness (usually in the later stages) in 10%–20% of cases 
• Olfactory dysfunction

Diagnosis

The typical duration of symptomatic Alzheimer disease is 8–10 years, but the course ranges from 1 to 25 years.

History and examination

• Detailed history, including the perspective of an informant (e.g., spouse or adult child)
• Neuropsychological assessment
• Mental status scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions to evaluate cognition:
  • Mini–Mental State Examination Mini–Mental State Examination Geriatric Changes ( MMSE MMSE Major Neurocognitive Disorders)
  • Montreal Cognitive Assessment Montreal Cognitive Assessment Major Neurocognitive Disorders ( MoCA MoCA Major Neurocognitive Disorders)
  • Alzheimer disease assessment scale-cognitive behavior subscale (ADAS-Cog)
  • Clinical Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders Rating Scale Scale Dermatologic Examination (CDR)

National Institute on Aging and the Alzheimer’s Association (NIA-AA) diagnostic guidelines

• Initial diagnostic criteria presented in 1984, revised in 2011:
  • Recognizes that Alzheimer disease presents on a spectrum with a preclinical stage, followed by early cognitive impairment, and then marked dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Expands the criteria beyond 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 loss to other cognitive aspects
• Criteria for probable Alzheimer disease dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders require the presence of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders and:
  • Interference with ability to function at work or usual activities
  • Decline from a previous level of functioning 
  • Not explained by 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 or major psychiatric disorder
  • Cognitive impairment established by history taking from the individual and a knowledgeable informant
  • Cognitive impairment involving ≥ 2 of the following:
    • Impaired ability to acquire and remember new information
    • Impaired reasoning Reasoning Decision-making Capacity and Legal Competence and handling of complex tasks, poor judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment
    • Impaired visuospatial abilities
    • Impaired language functions
    • Changes in personality, behavior, or comportment
  • Other clinical criteria:
    • Insidious onset
    • Clear history of progression
    • Initial and most prominent cognitive deficits are 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, or visuospatial cognitive deficits.
    • No other clear diagnosis of vascular dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders 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, or frontotemporal dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders

Other testing

• Labs to evaluate for other causes of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders:
  • CBC
  • Chemistries
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function
  • Vitamin B₁₂ 
• Imaging to rule out other pathology
  • MRI findings:
    • Generalized and focal 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
    • White matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome lesions
    • Reduced hippocampal volume or medial temporal lobe Temporal lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the occipital lobe. Cerebral Cortex: Anatomy 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 
  • Amyloid 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 imaging: Tracers may be used as qualitative assessments of beta-amyloid plaque Plaque Primary Skin Lesions density.

Management

There is no cure for Alzheimer disease, but medications may delay functional decline. Individualized treatment decisions are made in conjunction with individuals and caregivers after discussion of potential benefits, risks, and costs.

• Supportive care
  • Lifestyle modifications:
    • Regular Regular Insulin sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep cycle
    • It is imperative for the individual to stop driving when executive function is lost.
  • Maintain good physical health.
  • 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 training (e.g., puzzles, interactive games) 
• Pharmacologic treatment
  • Cholinesterase Cholinesterase Liver Function Tests inhibitors: used with mild to moderate symptoms
    • 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
    • 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
    • Galantamine Galantamine A benzazepine derived from norbelladine. It is found in galanthus and other amaryllidaceae. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of gallamine triethiodide and tubocurarine and has been studied as a treatment for alzheimer disease and other central nervous system disorders. Major Neurocognitive Disorders
  • N-methyl-D-aspartate (NMDA) antagonist:
    • Memantine
    • Used for moderate to severe dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Low-dose antipsychotics: only as a last resort to control 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 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
  • Selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants to treat concomitant depression
  • Monoclonal antibody against beta-amyloid:
    • Examples:
      • Aducanumab (approved 2021)
      • Lecanemab (approved 2023)
    • For mild cognitive impairment due to Alzheimer disease
    • Produced a substantial reduction 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 amyloid levels in studies, but benefits on clinical end points have been inconsistent
• Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies in families with a history of early-onset Alzheimer disease

Differential Diagnosis

• Vascular dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders: also known as multi-infarct dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders. Vascular dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders is caused by damage to the blood vessels and affects parts 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. The condition presents with abrupt cognitive decline and stepwise deterioration. Asymmetric focal deficits are the hallmark of this disease. Lacunar defects are seen on CT/MRI. Treatment includes risk factor reduction and managing hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, and hyperlipidemia and recommending smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation.
• Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders 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: Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, visual 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, parkinsonism Parkinsonism West Nile Virus, cognitive fluctuations, dysautonomia, sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disorders, and neuroleptic sensitivity are major symptoms of dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders 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. Diagnosed by white atrophic lesions seen on MRI. Treatment is supportive.
• Frontotemporal dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders: neuropathologically and clinically heterogeneous disorder characterized by focal degeneration 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/or temporal lobes. Frontotemporal dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders manifests between the ages of 45 and 70. The behavioral variant is most common and presents as early changes in behavior and apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome. Increased amyloid-beta protein is the primary indicator Indicator Methods for assessing flow through a system by injection of a known quantity of an indicator, such as a dye, radionuclide, or chilled liquid, into the system and monitoring its concentration over time at a specific point in the system. Body Fluid Compartments for frontotemporal dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, and changes in the temporal lobe Temporal lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the occipital lobe. Cerebral Cortex: Anatomy can be seen on 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 scans. Treatment is supportive.