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Alzheimer's disease may be classified into early onset and late onset based on age of onset:
Alzheimer's disease may be classified into early onset and late onset based on age of onset:


'''Early onset Alzheimer's disease'''
{| class="wikitable"
 
|'''Sub-class'''
'''Late onset onset Alzheimer's disease'''
|'''Genetics'''
|'''Prevalence'''
|-
| colspan="1" rowspan="1" |'''Late-onset familial (AD2)'''
|
* APOE gene:
** Locus: AD2
** Protein: Apolipoprotein E
* TREM2 gene:
** Variant: p.Arg47His allelic variant
* PLD3 gene
* UNC5C gene
* AKAP9 gene:
** In African-Americans only
| colspan="1" rowspan="1" |15%-25% of familial cases
|-
| colspan="1" rowspan="1" |'''Early-onset familial AD (AD1, AD3, AD4)'''
|
* PSEN1 gene:
** Locus: AD3
** Proportion: 20-70 % of early onset AD cases
** Protein: Presenilin-1
* PSEN2 gene:
** Locus: AD4
** Proportion: Rare
** Protein: Presenilin-2
* APP gene:
** Locus: AD1
** Proportion: 10-15 % of early onset AD cases
** Protein: Amyloid precursor protein (APP)
| colspan="1" rowspan="1" |<2% of familial cases
|}


=== Classification based on course of disease ===
=== Classification based on course of disease ===
'''Predementia'''
Alzheimer's disease may be classified into the following stages based on course of disease:<ref>{{cite journal
* The first symptoms are commonly misattributed to normal [[aging]] or [[Stress (medicine)|stress]].<ref name="pmid17222085">{{cite journal |author=Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B |title=Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline |journal=[[European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies]] |volume=14 |issue=1 |pages=e1–26 |year=2007 |month=January |pmid=17222085 |doi=10.1111/j.1468-1331.2006.01605.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1351-5101&date=2007&volume=14&issue=1&spage=e1 |accessdate=2012-08-15}}</ref> Detailed [[neuropsychology|neuropsychological]] testing can reveal mild cognitive difficulties up to eight years before a person meets the clinical criteria for the [[diagnosis]] of AD.<ref>Preclinical:
|author=Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A
*{{cite journal
|title=Sundowning and circadian rhythms in Alzheimer's disease
|author=Linn RT, Wolf PA, Bachman DL, ''et al''
|journal=Am J Psychiatry
|title=The 'preclinical phase' of probable Alzheimer's disease. A 13-year prospective study of the Framingham cohort
|volume=158
|journal=Arch. Neurol.
|volume=52
|issue=5
|issue=5
|pages=485–90
|pages=704–11
|year=1995
|year=2001
|month=May
|month=May
|pmid=7733843
|pmid=11329390
|accessdate=2008-08-04
|url=http://ajp.psychiatryonline.org/cgi/content/full/158/5/704
}}
|accessdate=2008-08-27
*{{cite journal
}}</ref><ref name="pmid12603249">{{cite journal
|author=Saxton J, Lopez OL, Ratcliff G, ''et al''
|title=Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset
|journal=Neurology
|volume=63
|issue=12
|pages=2341–7
|year=2004
|month=December
|pmid=15623697
}}
*{{cite journal
|author=Twamley EW, Ropacki SA, Bondi MW
|title=Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease
|journal=J Int Neuropsychol Soc
|volume=12
|issue=5
|pages=707–35
|year=2006
|month=September
|pmid=16961952
|pmc=1621044
|doi=10.1017/S1355617706060863
}}</ref> These early symptoms can affect the most complex [[Activities of daily living|daily living activities]].<ref name="pmid16513677">{{cite journal
|author=Perneczky R, Pohl C, Sorg C, Hartmann J, Komossa K, Alexopoulos P, Wagenpfeil S, Kurz A
|title=Complex activities of daily living in mild cognitive impairment: conceptual and diagnostic issues
|journal=Age Ageing
|volume=35
|issue=3
|pages=240–245
|year=2006
|pmid=16513677
|doi=10.1093/ageing/afj054
}}</ref> The most noticeable early deficit is [[memory loss]]. The patient has difficulty remembering recently learned facts and acquiring new information.<ref name="pmid12603249">{{cite journal
|author=Arnáiz E, Almkvist O
|author=Arnáiz E, Almkvist O
|title=Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease
|title=Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease
Line 142: Line 138:
|url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=DEM20050195_6331
|url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=DEM20050195_6331
|accessdate=2008-06-12
|accessdate=2008-06-12
}}</ref> Subtle problems with the [[executive functions]] of [[attention|attentiveness]], [[planning]], flexibility, and [[abstraction|abstract thinking]], or impairments in [[semantic memory]] (memory of meanings, and conceptual relationships), can also be symptomatic of the early stages of AD.<ref name="pmid15703322">{{cite journal
}}</ref><ref name="pmid15703322">{{cite journal
|author=Rapp MA, Reischies FM
|author=Rapp MA, Reischies FM
|title=Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE)
|title=Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE)
Line 163: Line 159:
|pmid=12754679
|pmid=12754679
}}
}}
</ref> [[Apathy]] may be observed at this stage, and remains the most persistent [[neuropsychiatry|neuropsychiatric]] symptom throughout the course of the disease.<ref name="pmid15956265">{{cite journal
</ref><ref name="pmid15956265">{{cite journal
|author=Craig D, Mirakhur A, Hart DJ, McIlroy SP, Passmore AP
|author=Craig D, Mirakhur A, Hart DJ, McIlroy SP, Passmore AP
|title=A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease |journal=American Journal of Geriatric Psychiatry
|title=A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease |journal=American Journal of Geriatric Psychiatry
Line 192: Line 188:
|pmid=17485646
|pmid=17485646
|doi=10.1212/01.wnl.0000260968.92345.3f
|doi=10.1212/01.wnl.0000260968.92345.3f
}}</ref> The preclinical stage of the disease has also been termed [[mild cognitive impairment]],<ref name="pmid17408315">{{cite journal
}}</ref><ref name="pmid10653284">{{cite journal
|author=Förstl H, Kurz A
|title=Clinical features of Alzheimer's disease
|journal=European Archives of Psychiatry and Clinical Neuroscience
|volume=249
|issue=6
|pages=288–290
|year=1999
|pmid=10653284
}}</ref><ref name="pmid17408315">{{cite journal
|author=Small BJ, Gagnon E, Robinson B
|author=Small BJ, Gagnon E, Robinson B
|title=Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment
|title=Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment
Line 202: Line 207:
|month=April
|month=April
|pmid=17408315
|pmid=17408315
}}</ref> though there is still debate about whether this term corresponds to a different and separate diagnostic entity or if it is simply a first step of Alzheimer's disease.<ref name="pmid17279076">{{cite journal
}}</ref><ref name="pmid17279076">{{cite journal
|author=Petersen RC
|author=Petersen RC
|title=The current status of mild cognitive impairment—what do we tell our patients?
|title=The current status of mild cognitive impairment—what do we tell our patients?
Line 213: Line 218:
|pmid=17279076
|pmid=17279076
|doi=10.1038/ncpneuro0402
|doi=10.1038/ncpneuro0402
}}</ref>
}}</ref><ref name="pmid7967534">{{cite journal
'''Early dementia'''
|author=Frank EM
 
|title=Effect of Alzheimer's disease on communication function
In people with AD the increasing impairment of [[learning]] and [[memory]] eventually leads to a definitive diagnosis.  In a small proportion of such patients, difficulties with language, [[executive functions]], [[perception]] ([[agnosia]]), or execution of movements ([[apraxia]]) are more prominent than memory problems.<ref name="pmid10653284">{{cite journal
|journal=J S C Med Assoc
|author=Förstl H, Kurz A
|volume=90
|title=Clinical features of Alzheimer's disease
|issue=9
|journal=European Archives of Psychiatry and Clinical Neuroscience
|pages=417–23
|volume=249
|year=1994
|issue=6
|month=September
|pages=288–290
|pmid=7967534
|year=1999
|pmid=10653284
}}</ref> AD does not affect all memory capacities equally. [[long-term memory|Older memories]] of the person's life ([[episodic memory]]), facts learned ([[semantic memory]]), and [[implicit memory]] (the memory of the body on how to do things, such as using a fork to eat) are less affected than new facts or memories.<ref name="pmid1300219">{{cite journal
|author=Carlesimo GA, Oscar-Berman M
|title=Memory deficits in Alzheimer's patients: a comprehensive review
|journal=Neuropsychol Rev
|volume=3
|issue=2
|pages=119–69
|year=1992
|month=June
|pmid=1300219
}}</ref><ref name="pmid8821346">{{cite journal
}}</ref><ref name="pmid8821346">{{cite journal
|author=Jelicic M, Bonebakker AE, Bonke B
|author=Jelicic M, Bonebakker AE, Bonke B
Line 245: Line 238:
|pmid=8821346
|pmid=8821346
| doi = 10.1017/S1041610295002134
| doi = 10.1017/S1041610295002134
}}</ref> [[semantic memory|Language problems]] include a shrinking [[vocabulary]] and decreased word [[fluency]], which lead to a general impoverishment of oral and written language. In this stage, the person with Alzheimer's is usually capable of adequately communicating basic ideas.<ref name="pmid7967534">{{cite journal
|author=Frank EM
|title=Effect of Alzheimer's disease on communication function
|journal=J S C Med Assoc
|volume=90
|issue=9
|pages=417–23
|year=1994
|month=September
|pmid=7967534
}}</ref><ref name="pmid12402233">{{cite journal
}}</ref><ref name="pmid12402233">{{cite journal
|author=Becker JT, Overman AA
|author=Becker JT, Overman AA
Line 275: Line 258:
|month=April
|month=April
|pmid=7617154
|pmid=7617154
}}</ref> Sufferers may appear clumsy when performing [[fine motor skill|fine motor tasks]] such as writing, drawing, or dressing, as their [[brain|brains]] have more difficulty with planning and coordinating certain movements ([[apraxia]]).<ref name="pmid8124945">{{cite journal
}}</ref><ref name="pmid8124945">{{cite journal
|author=Benke T
|author=Benke T
|title=Two forms of apraxia in Alzheimer's disease
|title=Two forms of apraxia in Alzheimer's disease
Line 285: Line 268:
|month=December
|month=December
|pmid=8124945
|pmid=8124945
}}</ref> As the disease progresses, people with AD often continue to perform many tasks independently, but may require assistance or supervision with cognitively demanding activities.<ref name="pmid10653284" />
}}</ref><ref name="pmid10653284" /><ref name="pmid15121235">{{cite journal
 
[[Image:Portion of Reagan's Alzheimer's letter.png|left|thumb|120px|In 1994 United States ex-president R. Reagan informed the country of his AD diagnosis via a hand-written letter.]]'''Moderate dementia'''
 
Progressive deterioration eventually hinders independence.<ref name="pmid10653284" /> [[Speech difficulties]] become more evident, with an inability to recall vocabulary leading to frequent incorrect word substitutions ([[paraphasia]]). Reading and writing skills are also progressively lost.<ref name="pmid7967534" /><ref name="pmid15121235">{{cite journal
|author=Forbes KE, Shanks MF, Venneri A
|author=Forbes KE, Shanks MF, Venneri A
|title=The evolution of dysgraphia in Alzheimer's disease
|title=The evolution of dysgraphia in Alzheimer's disease
Line 300: Line 279:
|pmid=15121235
|pmid=15121235
|doi=10.1016/j.brainresbull.2003.11.005
|doi=10.1016/j.brainresbull.2003.11.005
}}</ref> Complex motor sequences become less coordinated as time passes, reducing the ability to perform most normal daily activities.<ref name="pmid16209425">{{cite journal
}}</ref><ref name="pmid16209425">{{cite journal
|author=Galasko D, Schmitt F, Thomas R, Jin S, Bennett D
|author=Galasko D, Schmitt F, Thomas R, Jin S, Bennett D
|title=Detailed assessment of activities of daily living in moderate to severe Alzheimer's disease
|title=Detailed assessment of activities of daily living in moderate to severe Alzheimer's disease
Line 309: Line 288:
|year=2005
|year=2005
|pmid=16209425
|pmid=16209425
}}</ref> During this phase, memory problems worsen, and patients may fail to recognize close relatives.<ref name="pmid1737981">{{cite journal
}}</ref><ref>Neuropsychiatric symptoms:
|author=Galasko D, Schmitt F, Thomas R, Jin S, Bennett D
|title=Detailed assessment of activities of daily living in moderate to severe Alzheimer's disease
|journal=J Int Neuropsychol Soc
|volume=11
|issue=4
|pages=446–53
|year=2005
|month=July
|pmid=16209425
}}</ref> [[Long-term memory]], which was previously intact, becomes impaired,<ref name="pmid15288331">{{cite journal
|author=Sartori G, Snitz BE, Sorcinelli L, Daum I
|title=Remote memory in advanced Alzheimer's disease
|journal=Arch Clin Neuropsychol
|volume=19
|issue=6
|pages=779–89
|year=2004
|month=September
|pmid=15288331
|doi=10.1016/j.acn.2003.09.007
}}</ref> and behavioral changes become more prevalent. Common [[neuropsychiatric]] manifestations include wandering, sundowning (the onset of confusion and agitation each day around sundown),<ref>{{cite journal
|author=Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A
|title=Sundowning and circadian rhythms in Alzheimer's disease
|journal=Am J Psychiatry
|volume=158
|issue=5
|pages=704–11
|year=2001
|month=May
|pmid=11329390
|url=http://ajp.psychiatryonline.org/cgi/content/full/158/5/704
|accessdate=2008-08-27
}}</ref> [[irritability]], and [[labile affect]], which can lead to crying, outbursts of unpremeditated [[aggression]], or resistance to caregiving. Approximately 30% of patients also develop [[Delusional misidentification syndrome|illusionary misidentifications]] and other [[delusion]]al symptoms.<ref name="pmid15956265" /><ref>Neuropsychiatric symptoms:
*{{cite journal
*{{cite journal
|author=Scarmeas N, Brandt J, Blacker D, ''et al''
|author=Scarmeas N, Brandt J, Blacker D, ''et al''
Line 378: Line 324:
|pmid=17931577
|pmid=17931577
|doi=10.1016/j.jamda.2007.05.005
|doi=10.1016/j.jamda.2007.05.005
}}</ref> [[Urinary incontinence]] can develop.<ref name="pmid11442300">{{cite journal
}}</ref><ref name="pmid11442300">{{cite journal
|author=Honig LS, Mayeux R
|author=Honig LS, Mayeux R
|title=Natural history of Alzheimer's disease
|title=Natural history of Alzheimer's disease
Line 388: Line 334:
|month=June
|month=June
|pmid=11442300
|pmid=11442300
}}</ref> These symptoms create [[stress (medicine)|stress]] for relatives and caretakers, which can be reduced by moving the person from [[home care]] to a long-term care facility.<ref name="pmid10653284" /><ref name="pmid7806732">{{cite journal
}}</ref><ref name="pmid7806732">{{cite journal
|author=Gold DP, Reis MF, Markiewicz D, Andres D
|author=Gold DP, Reis MF, Markiewicz D, Andres D
|title=When home caregiving ends: a longitudinal study of outcomes for caregivers of relatives with dementia
|title=When home caregiving ends: a longitudinal study of outcomes for caregivers of relatives with dementia
Line 398: Line 344:
|month=January
|month=January
|pmid=7806732
|pmid=7806732
}}</ref>
}}</ref><ref name="pmid7775724">{{cite journal
 
'''Advanced dementia'''
 
During this last stage of AD, the patient is completely dependent upon caregivers. Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech.<ref name="pmid7967534" />
Despite the loss of verbal language abilities, patients can often understand and return emotional signals.<ref name="pmid14685735">{{cite journal
|author=Bär M, Kruse A, Re S
|title=[Situations of emotional significance in residents suffering from dementia]
|language=German
|journal=Z Gerontol Geriatr
|volume=36
|issue=6
|pages=454–62
|year=2003
|month=December
|pmid=14685735
|doi=10.1007/s00391-003-0191-0
}}</ref>
Although aggressiveness can still be present, extreme [[apathy]] and [[exhaustion]] are much more common.<ref name="pmid10653284" />
Patients will ultimately not be able to perform even the simplest tasks without assistance. [[musculature|Muscle mass]] and [[mobility]] deteriorate to the point where patients are bedridden<ref name="pmid7775724">{{cite journal
|author=Souren LE, Franssen EH, Reisberg B
|author=Souren LE, Franssen EH, Reisberg B
|title=Contractures and loss of function in patients with Alzheimer's disease
|title=Contractures and loss of function in patients with Alzheimer's disease
Line 427: Line 354:
|month=June
|month=June
|pmid=7775724
|pmid=7775724
}}</ref> and they lose the ability to feed themselves.<ref name="pmid12675103">{{cite journal
}}</ref><ref name="pmid11490146">{{cite journal
|author=Wada H, Nakajoh K, Satoh-Nakagawa T, ''et al''
|title=Risk factors of aspiration pneumonia in Alzheimer's disease patients
|journal=Gerontology
|volume=47
|issue=5
|pages=271–6
|year=2001
|pmid=11490146
}}</ref><ref name="pmid12675103">{{cite journal
|author=Berkhout AM, Cools HJ, van Houwelingen HC
|author=Berkhout AM, Cools HJ, van Houwelingen HC
|title=The relationship between difficulties in feeding oneself and loss of weight in nursing-home patients with dementia
|title=The relationship between difficulties in feeding oneself and loss of weight in nursing-home patients with dementia
Line 437: Line 373:
|month=September
|month=September
|pmid=12675103
|pmid=12675103
}}</ref>
When death comes, it is usually directly caused by some external factor such as [[bedsore|pressure ulcers]] or [[pneumonia]], rather than the disease itself.<ref name="pmid11490146">{{cite journal
|author=Wada H, Nakajoh K, Satoh-Nakagawa T, ''et al''
|title=Risk factors of aspiration pneumonia in Alzheimer's disease patients
|journal=Gerontology
|volume=47
|issue=5
|pages=271–6
|year=2001
|pmid=11490146
}}</ref><ref name="pmid10369823">{{cite journal
}}</ref><ref name="pmid10369823">{{cite journal
|author=Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R
|author=Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R
Line 459: Line 385:
|pmc=1736445
|pmc=1736445
}}</ref>
}}</ref>
<br clear="left" />
{| class="wikitable"
!Stage of Alzheime's disease
!Major deficits
|-
|Predementia
|
* Difficulty remembering recently learned facts and acquiring new information
* Disturbance of [[executive functions]] of [[attention|attentiveness]], [[planning]], flexibility, and [[abstraction|abstract thinking]], or impairments in [[semantic memory]] (memory of meanings, and conceptual relationships)
* Apathy
* Mild cognitive impairment
|-
|Early dementia
|
* Impairment of [[learning]] and [[memory]]
* Difficulties with language, [[executive functions]], [[perception]] ([[agnosia]]), or execution of movements ([[apraxia]]) are more prominent than memory problems
* [[long-term memory|Older memories]] of the person's life ([[episodic memory]]), facts learned ([[semantic memory]]), and [[implicit memory]] (the memory of the body on how to do things, such as using a fork to eat) are less affected than formation of new memories
* Decreased word fluency
* Cluminess when performing fine motor tasks such as writing, drawing or dressing
* Apraxia
* Noticeable cognitive impairment
|-
|Moderate dementia
|
* Speech disturbance (paraphasia)
* Reading and writing skills affected
* [[Long-term memory]], which was previously intact, becomes impaired
* Common [[neuropsychiatric]] manifestations include:
** Wandering
** Sundowning (the onset of confusion and agitation each day around sundown)
** Irritability
** Labile affect, which can lead to crying, outbursts of unpremeditated [[aggression]], or resistance to caregiving
** 30% of patients also develop [[Delusional misidentification syndrome|illusionary misidentifications]] and other [[delusion]]al symptoms
** Urinary incontinence
|-
|Advanced dementia
|
* Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech
* Extreme [[apathy]]
* Exhaustion
* Completely dependent on caregivers for daily tasks
* Decreased muscle mass, eventually becomes bedridden
|}
[[Image:Portion of Reagan's Alzheimer's letter.png|left|thumb|120px|In 1994 United States ex-president R. Reagan informed the country of his AD diagnosis via a hand-written letter.]]


==References==
==References==

Revision as of 01:04, 21 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2]; Haleigh Williams, B.S.

Overview

Classification

Classification based on severity

Alzheimer's disease may be classified based on the clinical dementia rating criteria into minimal, questionable, mild, moderate and severe in the following chart:

Clinical Dementia Rating
Based on the severity of Impairment
Criteria Minimal Questionable Mild Moderate Severe
Memory No memory loss or slight forgetfulness Consistent slight forgetfulness; partial recollection of events; “benign” forgetfulness Moderate memory loss; more marked for recent events; defect interferes with everyday activities Severe memory loss; only highly learned material retained; new material rapidly lost Severe memory loss; only fragments remain
Orientation Fully oriented Fully oriented except for slight difficulty with time relationships Moderate difficulty with time relationships; oriented for place at examination; may have geographic disorientation elsewhere Severe difficulty with time relationships; usually disoriented to time, often to place Oriented to person only
Judgment and problem solving Able to handle daily life activities (including financial issues); judgment good in relation to past performance Slight impairment in solving problems, determining similarities and differences Moderate difficulty in solving problems, determining similarities and differences; social judgment usually maintained Severely impaired in solving problems, determining similarities and differences; social judgment usually impaired Unable to make judgments or solve problems
Community affairs Functions independently and performs daily tasks such as shopping, and volunteer and social groups Slight impairment in these activities Unable to function independently at these activities, although may still be engaged in some; appears normal to casual inspection No pretense of independent function outside of home; appears well enough to be taken to functions outside a family home No pretense of independent function outside of home; appears too ill to be taken to functions outside a family home
Home and hobbies Life at home, hobbies, and intellectual interests well maintained Life at home, hobbies, and intellectual interests slightly impaired Mild but definite impairment of function at home; more difficult chores abandoned; more complicated hobbies and interests abandoned Only simple chores preserved; interests very restricted and poorly maintained No significant function in home
Personal care Fully capable of self-care Fully capable of self-care Needs prompting Requires assistance in dressing, hygiene, keeping of personal effects Requires much help with personal care; frequent incontinence

Classification based on age of onset

Alzheimer's disease may be classified into early onset and late onset based on age of onset:

Sub-class Genetics Prevalence
Late-onset familial (AD2)
  • APOE gene:
    • Locus: AD2
    • Protein: Apolipoprotein E
  • TREM2 gene:
    • Variant: p.Arg47His allelic variant
  • PLD3 gene
  • UNC5C gene
  • AKAP9 gene:
    • In African-Americans only
 15%-25% of familial cases
Early-onset familial AD (AD1, AD3, AD4)
  • PSEN1 gene:
    • Locus: AD3
    • Proportion: 20-70 % of early onset AD cases
    • Protein: Presenilin-1
  • PSEN2 gene:
    • Locus: AD4
    • Proportion: Rare
    • Protein: Presenilin-2
  • APP gene:
    • Locus: AD1
    • Proportion: 10-15 % of early onset AD cases
    • Protein: Amyloid precursor protein (APP)
 <2% of familial cases

Classification based on course of disease

Alzheimer's disease may be classified into the following stages based on course of disease:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][9][17][18][19][20][21][22][23][24][25]

Stage of Alzheime's disease Major deficits
Predementia
Early dementia
Moderate dementia
  • Speech disturbance (paraphasia)
  • Reading and writing skills affected
  • Long-term memory, which was previously intact, becomes impaired
  • Common neuropsychiatric manifestations include:
    • Wandering
    • Sundowning (the onset of confusion and agitation each day around sundown)
    • Irritability
    • Labile affect, which can lead to crying, outbursts of unpremeditated aggression, or resistance to caregiving
    • 30% of patients also develop illusionary misidentifications and other delusional symptoms
    • Urinary incontinence
Advanced dementia
  • Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech
  • Extreme apathy
  • Exhaustion
  • Completely dependent on caregivers for daily tasks
  • Decreased muscle mass, eventually becomes bedridden
In 1994 United States ex-president R. Reagan informed the country of his AD diagnosis via a hand-written letter.

References

  1. ↑ Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A (2001). "Sundowning and circadian rhythms in Alzheimer's disease". Am J Psychiatry. 158 (5): 704–11. PMID 11329390. Retrieved 2008-08-27. Unknown parameter |month= ignored (help)
  2. ↑ Arnáiz E, Almkvist O (2003). "Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease". Acta Neurol. Scand., Suppl. 179: 34–41. doi:10.1034/j.1600-0404.107.s179.7.x. PMID 12603249. |access-date= requires |url= (help)
  3. ↑ Kazui H, Matsuda A, Hirono N; et al. (2005). "Everyday memory impairment of patients with mild cognitive impairment". Dement Geriatr Cogn Disord. 19 (5–6): 331–7. doi:10.1159/000084559. PMID 15785034. Retrieved 2008-06-12.
  4. ↑ Rapp MA, Reischies FM (2005). "Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE)". American Journal of Geriatric Psychiatry. 13 (2): 134–141. doi:10.1176/appi.ajgp.13.2.134. PMID 15703322.
  5. ↑ Spaan PE, Raaijmakers JG, Jonker C (2003). "Alzheimer's disease versus normal ageing: a review of the efficiency of clinical and experimental memory measures". Journal of Clinical Experimental Neuropsychology. 25 (2): 216–233. PMID 12754679.
  6. ↑ Craig D, Mirakhur A, Hart DJ, McIlroy SP, Passmore AP (2005). "A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease". American Journal of Geriatric Psychiatry. 13 (6): 460–468. doi:10.1176/appi.ajgp.13.6.460. PMID 15956265.
  7. ↑ Robert PH, Berr C, Volteau M, Bertogliati C, Benoit M, Sarazin M, Legrain S, Dubois B (2006). "Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer's disease: a one-year follow-up study". Clin Neurol Neurosurg. 108 (8): 733–736. doi:10.1016/j.clineuro.2006.02.003. PMID 16567037.
  8. ↑ Palmer K, Berger AK, Monastero R, Winblad B, Bäckman L, Fratiglioni L (2007). "Predictors of progression from mild cognitive impairment to Alzheimer disease". Neurology. 68 (19): 1596–1602. doi:10.1212/01.wnl.0000260968.92345.3f. PMID 17485646.
  9. ↑ 9.0 9.1 Förstl H, Kurz A (1999). "Clinical features of Alzheimer's disease". European Archives of Psychiatry and Clinical Neuroscience. 249 (6): 288–290. PMID 10653284.
  10. ↑ Small BJ, Gagnon E, Robinson B (2007). "Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment". Geriatrics. 62 (4): 19–23. PMID 17408315. Unknown parameter |month= ignored (help)
  11. ↑ Petersen RC (2007). "The current status of mild cognitive impairment—what do we tell our patients?". Nat Clin Pract Neurol. 3 (2): 60–1. doi:10.1038/ncpneuro0402. PMID 17279076. Unknown parameter |month= ignored (help)
  12. ↑ Frank EM (1994). "Effect of Alzheimer's disease on communication function". J S C Med Assoc. 90 (9): 417–23. PMID 7967534. Unknown parameter |month= ignored (help)
  13. ↑ Jelicic M, Bonebakker AE, Bonke B (1995). "Implicit memory performance of patients with Alzheimer's disease: a brief review". International Psychogeriatrics. 7 (3): 385–392. doi:10.1017/S1041610295002134. PMID 8821346.
  14. ↑ Becker JT, Overman AA (2002). "[The semantic memory deficit in Alzheimer's disease]". Rev Neurol (in Spanish; Castilian). 35 (8): 777–83. PMID 12402233.
  15. ↑ Hodges JR, Patterson K (1995). "Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications". Neuropsychologia. 33 (4): 441–59. PMID 7617154. Unknown parameter |month= ignored (help)
  16. ↑ Benke T (1993). "Two forms of apraxia in Alzheimer's disease". Cortex. 29 (4): 715–25. PMID 8124945. Unknown parameter |month= ignored (help)
  17. ↑ Forbes KE, Shanks MF, Venneri A (2004). "The evolution of dysgraphia in Alzheimer's disease". Brain Res. Bull. 63 (1): 19–24. doi:10.1016/j.brainresbull.2003.11.005. PMID 15121235. Unknown parameter |month= ignored (help)
  18. ↑ Galasko D, Schmitt F, Thomas R, Jin S, Bennett D (2005). "Detailed assessment of activities of daily living in moderate to severe Alzheimer's disease". Journal of the International Neuropsychology Society. 11 (4): 446–453. PMID 16209425.
  19. ↑ Neuropsychiatric symptoms:
    • Scarmeas N, Brandt J, Blacker D; et al. (2007). "Disruptive behavior as a predictor in Alzheimer disease". Arch. Neurol. 64 (12): 1755–61. doi:10.1001/archneur.64.12.1755. PMID 18071039. Unknown parameter |month= ignored (help)
    • Tatsch MF, Bottino CM, Azevedo D; et al. (2006). "Neuropsychiatric symptoms in Alzheimer disease and cognitively impaired, nondemented elderly from a community-based sample in Brazil: prevalence and relationship with dementia severity". Am J Geriatr Psychiatry. 14 (5): 438–45. doi:10.1097/01.JGP.0000218218.47279.db. PMID 16670248. Unknown parameter |month= ignored (help)
    • Volicer L, Bass EA, Luther SL (2007). "Agitation and resistiveness to care are two separate behavioral syndromes of dementia". J Am Med Dir Assoc. 8 (8): 527–32. doi:10.1016/j.jamda.2007.05.005. PMID 17931577. Unknown parameter |month= ignored (help)
  20. ↑ Honig LS, Mayeux R (2001). "Natural history of Alzheimer's disease". Aging (Milano). 13 (3): 171–82. PMID 11442300. Unknown parameter |month= ignored (help)
  21. ↑ Gold DP, Reis MF, Markiewicz D, Andres D (1995). "When home caregiving ends: a longitudinal study of outcomes for caregivers of relatives with dementia". J Am Geriatr Soc. 43 (1): 10–6. PMID 7806732. Unknown parameter |month= ignored (help)
  22. ↑ Souren LE, Franssen EH, Reisberg B (1995). "Contractures and loss of function in patients with Alzheimer's disease". J Am Geriatr Soc. 43 (6): 650–5. PMID 7775724. Unknown parameter |month= ignored (help)
  23. ↑ Wada H, Nakajoh K, Satoh-Nakagawa T; et al. (2001). "Risk factors of aspiration pneumonia in Alzheimer's disease patients". Gerontology. 47 (5): 271–6. PMID 11490146.
  24. ↑ Berkhout AM, Cools HJ, van Houwelingen HC (1998). "The relationship between difficulties in feeding oneself and loss of weight in nursing-home patients with dementia". Age Ageing. 27 (5): 637–41. PMID 12675103. Unknown parameter |month= ignored (help)
  25. ↑ Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R (1999). "Predictors of mortality in patients with Alzheimer's disease living in nursing homes". J. Neurol. Neurosurg. Psychiatr. 67 (1): 59–65. PMC 1736445. PMID 10369823. Unknown parameter |month= ignored (help)

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