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Alzheimer disease 3(AD3)

MedGen UID:
334304
Concept ID:
C1843013
Disease or Syndrome
Synonyms: AD3; Alzheimer disease early onset type 3; ALZHEIMER DISEASE, FAMILIAL, 3
 
Genes (locations): APOE (19q13.32); PSEN1 (14q24.2)
 
Monarch Initiative: MONDO:0011913
OMIM®: 607822

Definition

Alzheimer's disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear between a person's thirties and mid-sixties, while the late-onset form appears during or after a person's mid-sixties. The early-onset form of Alzheimer's disease is much less common than the late-onset form, accounting for less than 10 percent of all cases of Alzheimer's disease.

As the disorder progresses, some people with Alzheimer's disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with Alzheimer's disease usually require total care during the advanced stages of the disease.

Memory loss is the most common sign of Alzheimer's disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer's disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.

Individuals with Alzheimer's disease usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Survival is usually shorter in individuals diagnosed after age 80 than in those diagnosed at a younger age. In Alzheimer's disease, death usually results from pneumonia, malnutrition, or general body wasting (inanition).

Alzheimer's disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood. [from MedlinePlus Genetics]

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Alzheimer disease
MedGen UID:
1853
Concept ID:
C0002395
Disease or Syndrome
Alzheimer's disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood.\n\nIndividuals with Alzheimer's disease usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Survival is usually shorter in individuals diagnosed after age 80 than in those diagnosed at a younger age. In Alzheimer's disease, death usually results from pneumonia, malnutrition, or general body wasting (inanition).\n\nMemory loss is the most common sign of Alzheimer's disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer's disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.\n\nAs the disorder progresses, some people with Alzheimer's disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with Alzheimer's disease usually require total care during the advanced stages of the disease.\n\nAlzheimer's disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear between a person's thirties and mid-sixties, while the late-onset form appears during or after a person's mid-sixties. The early-onset form of Alzheimer's disease is much less common than the late-onset form, accounting for less than 10 percent of all cases of Alzheimer's disease.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Neurofibrillary tangles
MedGen UID:
39273
Concept ID:
C0085400
Finding
Pathological protein aggregates formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form.
Disturbed sensory perception
MedGen UID:
508504
Concept ID:
C0150075
Finding
Alteration or impairment in the processing or interpretation of sensory information can lead to abnormal perceptions or experiences.
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Optic ataxia
MedGen UID:
1635801
Concept ID:
C4703584
Finding
Difficulty reaching visually guided goals in peripheral vision, with the deficit, leaves voluntary eye movements largely unaffected.

Professional guidelines

PubMed

Kadakova S, Raska J, Hribkova H, Fedorova V, Sedmik J, Plesingrova K, Sheardova K, Bohaciakova D
Stem Cell Res 2024 Feb;74:103273. Epub 2023 Dec 7 doi: 10.1016/j.scr.2023.103273. PMID: 38100913

Recent clinical studies

Etiology

Zukotynski K, Black SE, Kuo PH, Bhan A, Adamo S, Scott CJM, Lam B, Masellis M, Kumar S, Fischer CE, Tartaglia MC, Lang AE, Tang-Wai DF, Freedman M, Vasdev N, Gaudet V
Clin Nucl Med 2021 Aug 1;46(8):616-620. doi: 10.1097/RLU.0000000000003668. PMID: 33883495
Cohen AD, McDade E, Christian B, Price J, Mathis C, Klunk W, Handen BL
Alzheimers Dement 2018 Jun;14(6):743-750. Epub 2018 Mar 1 doi: 10.1016/j.jalz.2018.01.002. PMID: 29477284Free PMC Article
Zerah L, Boddaert J, Leperre-Desplanques A, Bonnet-Zamponi D, Verny M, Deligne J, Boelle PY
J Am Med Dir Assoc 2017 Jun 1;18(6):549.e1-549.e13. Epub 2017 Mar 18 doi: 10.1016/j.jamda.2017.02.001. PMID: 28330633
Shadlen MF, McCormick WC, Larson EB
Alzheimer Dis Assoc Disord 2002;16 Suppl 2:S96-S100. doi: 10.1097/00002093-200200002-00012. PMID: 12351923
Stopa EG, Volicer L, Kuo-Leblanc V, Harper D, Lathi D, Tate B, Satlin A
J Neuropathol Exp Neurol 1999 Jan;58(1):29-39. doi: 10.1097/00005072-199901000-00004. PMID: 10068311

Diagnosis

Zukotynski K, Black SE, Kuo PH, Bhan A, Adamo S, Scott CJM, Lam B, Masellis M, Kumar S, Fischer CE, Tartaglia MC, Lang AE, Tang-Wai DF, Freedman M, Vasdev N, Gaudet V
Clin Nucl Med 2021 Aug 1;46(8):616-620. doi: 10.1097/RLU.0000000000003668. PMID: 33883495
Cohen AD, McDade E, Christian B, Price J, Mathis C, Klunk W, Handen BL
Alzheimers Dement 2018 Jun;14(6):743-750. Epub 2018 Mar 1 doi: 10.1016/j.jalz.2018.01.002. PMID: 29477284Free PMC Article
Zerah L, Boddaert J, Leperre-Desplanques A, Bonnet-Zamponi D, Verny M, Deligne J, Boelle PY
J Am Med Dir Assoc 2017 Jun 1;18(6):549.e1-549.e13. Epub 2017 Mar 18 doi: 10.1016/j.jamda.2017.02.001. PMID: 28330633
MacPherson SE, Parra MA, Moreno S, Lopera F, Della Sala S
J Alzheimers Dis 2015;44(2):481-92. doi: 10.3233/JAD-140990. PMID: 25352452
Hollister LE, Shah NN
J Clin Psychiatry 1996 Jun;57(6):241-4. PMID: 8666560

Therapy

Alvarado CX, Makarious MB, Weller CA, Vitale D, Koretsky MJ, Bandres-Ciga S, Iwaki H, Levine K, Singleton A, Faghri F, Nalls MA, Leonard HL
Am J Hum Genet 2024 Jan 4;111(1):150-164. doi: 10.1016/j.ajhg.2023.12.006. PMID: 38181731Free PMC Article
Zerah L, Boddaert J, Leperre-Desplanques A, Bonnet-Zamponi D, Verny M, Deligne J, Boelle PY
J Am Med Dir Assoc 2017 Jun 1;18(6):549.e1-549.e13. Epub 2017 Mar 18 doi: 10.1016/j.jamda.2017.02.001. PMID: 28330633
Shadlen MF, McCormick WC, Larson EB
Alzheimer Dis Assoc Disord 2002;16 Suppl 2:S96-S100. doi: 10.1097/00002093-200200002-00012. PMID: 12351923

Prognosis

Hollister LE, Shah NN
J Clin Psychiatry 1996 Jun;57(6):241-4. PMID: 8666560

Clinical prediction guides

Zukotynski K, Black SE, Kuo PH, Bhan A, Adamo S, Scott CJM, Lam B, Masellis M, Kumar S, Fischer CE, Tartaglia MC, Lang AE, Tang-Wai DF, Freedman M, Vasdev N, Gaudet V
Clin Nucl Med 2021 Aug 1;46(8):616-620. doi: 10.1097/RLU.0000000000003668. PMID: 33883495
Stopa EG, Volicer L, Kuo-Leblanc V, Harper D, Lathi D, Tate B, Satlin A
J Neuropathol Exp Neurol 1999 Jan;58(1):29-39. doi: 10.1097/00005072-199901000-00004. PMID: 10068311
Hollister LE, Shah NN
J Clin Psychiatry 1996 Jun;57(6):241-4. PMID: 8666560

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