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Alzheimer disease(AD)

MedGen UID:
1853
Concept ID:
C0002395
Disease or Syndrome
Synonyms: Alzheimer's disease; Presenile and senile dementia
SNOMED CT: AD - Alzheimer's disease (26929004); Alzheimer disease (26929004); Alzheimer dementia (26929004); Alzheimer's disease (26929004)
 
Gene (location): APP (21q21.3)
Related genes: ABCA7, PSEN2, PSEN1, PLAU, NOS3, MPO, APOE
 
HPO: HP:0002511
Monarch Initiative: MONDO:0004975
OMIM®: 104300; 516000
Orphanet: ORPHA238616

Definition

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.

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.

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.

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 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. [from MedlinePlus Genetics]

Conditions with this feature

Down syndrome
MedGen UID:
4385
Concept ID:
C0013080
Disease or Syndrome
Down syndrome, the most frequent form of mental retardation caused by a microscopically demonstrable chromosomal aberration, is characterized by well-defined and distinctive phenotypic features and natural history. It is caused by triplicate state (trisomy) of all or a critical portion of chromosome 21.
Alzheimer disease 3
MedGen UID:
334304
Concept ID:
C1843013
Disease or Syndrome
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.\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\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\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\nAlzheimer'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.
Alzheimer disease 4
MedGen UID:
376072
Concept ID:
C1847200
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\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\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\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.
Alzheimer disease, familial early-onset, with coexisting amyloid and prion pathology
MedGen UID:
341884
Concept ID:
C1857933
Disease or Syndrome
Alzheimer disease 2
MedGen UID:
400197
Concept ID:
C1863051
Disease or Syndrome
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.\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\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\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\nAlzheimer'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.
Alzheimer disease type 1
MedGen UID:
354892
Concept ID:
C1863052
Disease or Syndrome
Alzheimer disease is the most common form of progressive dementia in the elderly. It is a neurodegenerative disorder characterized by the neuropathologic findings of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques that accumulate in vulnerable brain regions (Sennvik et al., 2000). Terry and Davies (1980) pointed out that the 'presenile' form, with onset before age 65, is identical to the most common form of late-onset or 'senile' dementia, and suggested the term 'senile dementia of the Alzheimer type' (SDAT). Haines (1991) reviewed the genetics of AD. Selkoe (1996) reviewed the pathophysiology, chromosomal loci, and pathogenetic mechanisms of Alzheimer disease. Theuns and Van Broeckhoven (2000) reviewed the transcriptional regulation of the genes involved in Alzheimer disease. Genetic Heterogeneity of Alzheimer Disease Alzheimer disease is a genetically heterogeneous disorder. See also AD2 (104310), associated with the APOE*4 allele (107741) on chromosome 19; AD3 (607822), caused by mutation in the presenilin-1 gene (PSEN1; 104311) on 14q; and AD4 (606889), caused by mutation in the PSEN2 gene (600759) on 1q31. There is evidence for additional AD loci on other chromosomes; see AD5 (602096) on 12p11; AD6 (605526) on 10q24; AD7 (606187) on 10p13; AD8 (607116) on 20p; AD9 (608907), associated with variation in the ABCA7 gene (605414) on 19p13; AD10 (609636) on 7q36; AD11 (609790) on 9q22; AD12 (611073) on 8p12-q22; AD13 (611152) on 1q21; AD14 (611154) on 1q25; AD15 (604154) on 3q22-q24; AD16 (300756) on Xq21.3; AD17 (615080) on 6p21.2; and AD18 (615590), associated with variation in the ADAM10 gene (602192) on 15q21. Evidence also suggests that mitochondrial DNA polymorphisms may be risk factors in Alzheimer disease (502500). Finally, there have been associations between AD and various polymorphisms in other genes, including alpha-2-macroglobulin (A2M; 103950.0005), low density lipoprotein-related protein-1 (LRP1; 107770), the transferrin gene (TF; 190000), the hemochromatosis gene (HFE; 613609), the NOS3 gene (163729), the vascular endothelial growth factor gene (VEGF; 192240), the ABCA2 gene (600047), and the TNF gene (191160) (see MOLECULAR GENETICS).
Alzheimer disease 10
MedGen UID:
351228
Concept ID:
C1864828
Disease or Syndrome
An Alzheimer's disease that is characterized by an associated with variation in the region 7q36.
Alzheimer disease 5
MedGen UID:
356103
Concept ID:
C1865868
Disease or Syndrome
Alzheimer disease 9
MedGen UID:
924255
Concept ID:
C4282179
Finding

Professional guidelines

PubMed

Arvanitakis Z, Shah RC, Bennett DA
JAMA 2019 Oct 22;322(16):1589-1599. doi: 10.1001/jama.2019.4782. PMID: 31638686Free PMC Article
Long JM, Holtzman DM
Cell 2019 Oct 3;179(2):312-339. Epub 2019 Sep 26 doi: 10.1016/j.cell.2019.09.001. PMID: 31564456Free PMC Article
McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O'Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K
Neurology 2017 Jul 4;89(1):88-100. Epub 2017 Jun 7 doi: 10.1212/WNL.0000000000004058. PMID: 28592453Free PMC Article

Recent clinical studies

Etiology

Wong W
Am J Manag Care 2020 Aug;26(8 Suppl):S177-S183. doi: 10.37765/ajmc.2020.88482. PMID: 32840331
Grabher BJ
J Nucl Med Technol 2018 Dec;46(4):335-340. Epub 2018 Aug 23 doi: 10.2967/jnmt.118.218057. PMID: 30139888
Eratne D, Loi SM, Farrand S, Kelso W, Velakoulis D, Looi JC
Australas Psychiatry 2018 Aug;26(4):347-357. Epub 2018 Apr 3 doi: 10.1177/1039856218762308. PMID: 29614878
Gómez Gallego M, Gómez García J
Neurologia 2017 Jun;32(5):300-308. Epub 2016 Feb 17 doi: 10.1016/j.nrl.2015.12.003. PMID: 26896913
Oboudiyat C, Glazer H, Seifan A, Greer C, Isaacson RS
Semin Neurol 2013 Sep;33(4):313-29. Epub 2013 Nov 14 doi: 10.1055/s-0033-1359319. PMID: 24234352

Diagnosis

Grabher BJ
J Nucl Med Technol 2018 Dec;46(4):335-340. Epub 2018 Aug 23 doi: 10.2967/jnmt.118.218057. PMID: 30139888
Tellechea P, Pujol N, Esteve-Belloch P, Echeveste B, García-Eulate MR, Arbizu J, Riverol M
Neurologia (Engl Ed) 2018 May;33(4):244-253. Epub 2015 Nov 3 doi: 10.1016/j.nrl.2015.08.002. PMID: 26546285
Mendez MF
Neurol Clin 2017 May;35(2):263-281. doi: 10.1016/j.ncl.2017.01.005. PMID: 28410659Free PMC Article
EBioMedicine 2016 Jul;9:1-2. Epub 2016 Jul 5 doi: 10.1016/j.ebiom.2016.07.001. PMID: 27412262Free PMC Article
Brody H
Nature 2011 Jul 13;475(7355):S1. doi: 10.1038/475S1a. PMID: 21760574

Therapy

Boxer AL, Sperling R
Cell 2023 Oct 26;186(22):4757-4772. Epub 2023 Oct 16 doi: 10.1016/j.cell.2023.09.023. PMID: 37848035Free PMC Article
Kurkinen M
Adv Clin Exp Med 2023 Sep;32(9):943-947. doi: 10.17219/acem/171379. PMID: 37676096
Flo BK, Matziorinis AM, Skouras S, Sudmann TT, Gold C, Koelsch S
PLoS One 2022;17(6):e0270682. Epub 2022 Jun 30 doi: 10.1371/journal.pone.0270682. PMID: 35771851Free PMC Article
Avgerinos KI, Ferrucci L, Kapogiannis D
Ageing Res Rev 2021 Jul;68:101339. Epub 2021 Apr 5 doi: 10.1016/j.arr.2021.101339. PMID: 33831607Free PMC Article
Yeung CHC, Schooling CM
Int J Epidemiol 2021 Jul 9;50(3):829-840. doi: 10.1093/ije/dyaa241. PMID: 33313759

Prognosis

Alzheimers Dement 2021 Mar;17(3):327-406. Epub 2021 Mar 23 doi: 10.1002/alz.12328. PMID: 33756057
Silva MVF, Loures CMG, Alves LCV, de Souza LC, Borges KBG, Carvalho MDG
J Biomed Sci 2019 May 9;26(1):33. doi: 10.1186/s12929-019-0524-y. PMID: 31072403Free PMC Article
Niu H, Álvarez-Álvarez I, Guillén-Grima F, Aguinaga-Ontoso I
Neurologia 2017 Oct;32(8):523-532. Epub 2016 Apr 26 doi: 10.1016/j.nrl.2016.02.016. PMID: 27130306
Sacuiu SF
Handb Clin Neurol 2016;138:123-51. doi: 10.1016/B978-0-12-802973-2.00008-2. PMID: 27637956
Qiu C, Kivipelto M, von Strauss E
Dialogues Clin Neurosci 2009;11(2):111-28. doi: 10.31887/DCNS.2009.11.2/cqiu. PMID: 19585947Free PMC Article

Clinical prediction guides

Ibrahim B, Suppiah S, Ibrahim N, Mohamad M, Hassan HA, Nasser NS, Saripan MI
Hum Brain Mapp 2021 Jun 15;42(9):2941-2968. Epub 2021 May 4 doi: 10.1002/hbm.25369. PMID: 33942449Free PMC Article
Wang X, Zhen X, Li Q, Shen D, Huang H
Neuroinformatics 2018 Oct;16(3-4):285-294. doi: 10.1007/s12021-018-9381-1. PMID: 29802511Free PMC Article
Wattmo C
Am J Alzheimers Dis Other Demen 2013 Aug;28(5):440-9. Epub 2013 May 20 doi: 10.1177/1533317513488916. PMID: 23689074Free PMC Article
Mandal PK
J Alzheimers Dis 2012;31 Suppl 3:S1-3. doi: 10.3233/JAD-2012-120731. PMID: 22903126
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J
Neurology 1994 Dec;44(12):2308-14. doi: 10.1212/wnl.44.12.2308. PMID: 7991117

Recent systematic reviews

Kim KY, Shin KY, Chang KA
Cells 2023 May 4;12(9) doi: 10.3390/cells12091309. PMID: 37174709Free PMC Article
Bleibel M, El Cheikh A, Sadier NS, Abou-Abbas L
Alzheimers Res Ther 2023 Mar 27;15(1):65. doi: 10.1186/s13195-023-01214-9. PMID: 36973733Free PMC Article
Chou YH, Sundman M, Ton That V, Green J, Trapani C
Ageing Res Rev 2022 Aug;79:101660. Epub 2022 Jun 6 doi: 10.1016/j.arr.2022.101660. PMID: 35680080Free PMC Article
Solch RJ, Aigbogun JO, Voyiadjis AG, Talkington GM, Darensbourg RM, O'Connell S, Pickett KM, Perez SR, Maraganore DM
J Neurol Sci 2022 Mar 15;434:120166. Epub 2022 Jan 26 doi: 10.1016/j.jns.2022.120166. PMID: 35144237
Blackman J, Swirski M, Clynes J, Harding S, Leng Y, Coulthard E
J Sleep Res 2021 Aug;30(4):e13229. Epub 2020 Dec 2 doi: 10.1111/jsr.13229. PMID: 33289311Free PMC Article

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2023 Statement from the US Food and Drug Administration (FDA):

Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer’s disease patients) treated with this class of medications, including [lecanemab], have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed they can still be treated with lecanemab; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA… Consider the benefit of lecanemab for the treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when decided to initiate treatment with lecanemab.

Please review the complete therapeutic recommendations that are located here: (1).

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes, and genetic variants may be corrected in accordance with nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.

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