Alzheimer's disease classification: Difference between revisions

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{{CMG}}; {{AE}} {{HW}}
__NOTOC__
{{Alzheimer's disease}}
{{Alzheimer's disease}}
{{CMG}}; {{AE}} {{HK}}, {{ARK}}, {{HW}}
==Overview==
Alzheimer's disease may be classified according to severity into mild, moderate and severe [[dementia]]. It may also be classified based on age of onset into early onset and late onset Alzheimer's disease. Another method of classification of Alzheimer's disease is based on the course of [[disease]] into pre-[[dementia]], early [[dementia]], moderate [[dementia]] and advanced [[dementia]].


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


===Classification based on severity===
Alzheimer's disease may be classified based on the clinical [[dementia]] rating criteria into minimal, intermediate, mild, moderate and severe:<ref name="pmid9447441">{{cite journal |vauthors=Morris JC |title=Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type |journal=Int Psychogeriatr |volume=9 Suppl 1 |issue= |pages=173–6; discussion 177–8 |year=1997 |pmid=9447441 |doi= |url=}}</ref><ref name="pmid3249765">{{cite journal |vauthors=Berg L |title=Clinical Dementia Rating (CDR) |journal=Psychopharmacol Bull |volume=24 |issue=4 |pages=637–9 |year=1988 |pmid=3249765 |doi= |url=}}</ref><ref name="pmid18695059">{{cite journal |vauthors=O'Bryant SE, Waring SC, Cullum CM, Hall J, Lacritz L, Massman PJ, Lupo PJ, Reisch JS, Doody R |title=Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study |journal=Arch. Neurol. |volume=65 |issue=8 |pages=1091–5 |year=2008 |pmid=18695059 |pmc=3409562 |doi=10.1001/archneur.65.8.1091 |url=}}</ref><ref name="pmid8232972">{{cite journal |vauthors=Morris JC |title=The Clinical Dementia Rating (CDR): current version and scoring rules |journal=Neurology |volume=43 |issue=11 |pages=2412–4 |year=1993 |pmid=8232972 |doi= |url=}}</ref><ref name="pmid9191756">{{cite journal |vauthors=Morris JC, Ernesto C, Schafer K, Coats M, Leon S, Sano M, Thal LJ, Woodbury P |title=Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience |journal=Neurology |volume=48 |issue=6 |pages=1508–10 |year=1997 |pmid=9191756 |doi= |url=}}</ref>
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
| colspan="6" style="background: #4479BA; text-align: center;" | {{fontcolor|#FFF|'''Clinical Dementia Rating'''}}
| colspan="6" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF|'''Clinical Dementia Rating'''}}
|+
|-
| colspan="6" style="background: #4479BA; text-align: center;" | {{fontcolor|#FFF|'''Based on Impairment'''}}
| colspan="6" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF|'''Based on the severity of Impairment'''}}
|+  
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF| }}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Criteria}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Minimal}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Minimal}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Questionable}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Indeterminate}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Mild}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Mild}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Moderate}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Moderate}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Severe}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Severe}}
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Memory}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Memory}}
| style="padding: 5px 5px; background: #F5F5F5;" | No memory loss or slight inconsistent forgetfulness
| style="padding: 5px 5px; background: #F5F5F5;" |No [[memory loss]] or slight [[forgetfulness]]
| style="padding: 5px 5px; background: #F5F5F5;" | Consistent slight forgetfulness; partial recollection of events; “benign” forgetfulness
| style="padding: 5px 5px; background: #F5F5F5;" |Minimal [[forgetfulness]]; partial recollection of events; “benign” [[forgetfulness]]
| style="padding: 5px 5px; background: #F5F5F5;" | Moderate memory loss; more marked for recent events; defect interferes with everyday activities
| style="padding: 5px 5px; background: #F5F5F5;" |Moderate [[memory loss]]; more marked for recent events; defect interferes with everyday activities
| style="padding: 5px 5px; background: #F5F5F5;" | Severe memory loss; only highly learned material retained; new material rapidly lost
| style="padding: 5px 5px; background: #F5F5F5;" |Severe [[memory loss]]; only highly learned material retained; new material rapidly lost
| style="padding: 5px 5px; background: #F5F5F5;" | Severe memory loss; only fragments remain
| style="padding: 5px 5px; background: #F5F5F5;" |Severe [[memory loss]]; only fragments remain
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Orientation}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Orientation}}
| style="padding: 5px 5px; background: #F5F5F5;" | Fully oriented
| style="padding: 5px 5px; background: #F5F5F5;" |Fully oriented
| style="padding: 5px 5px; background: #F5F5F5;" | Fully oriented except for slight difficulty with time relationships
| style="padding: 5px 5px; background: #F5F5F5;" |Fully oriented except for slight difficulty with time [[perception]]
| style="padding: 5px 5px; background: #F5F5F5;" | Moderate difficulty with time relationships; oriented for place at examination; may have geographic disorientation elsewhere
| style="padding: 5px 5px; background: #F5F5F5;" |Moderate difficulty with time perception; oriented for place at examination; may be disoriented to place
| style="padding: 5px 5px; background: #F5F5F5;" | Severe difficulty with time relationships; usually disoriented to time, often to place
| style="padding: 5px 5px; background: #F5F5F5;" |Severe difficulty with time relationships; usually [[Disorientation|disoriented]] to time, often to place
| style="padding: 5px 5px; background: #F5F5F5;" | Oriented to person only
| style="padding: 5px 5px; background: #F5F5F5;" |Oriented to person only
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Judgment and problem solving}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Judgment and problem solving}}
| style="padding: 5px 5px; background: #F5F5F5;" | Solves everyday problems and handles business and financial affairs well; judgment good in relation to past performance
| style="padding: 5px 5px; background: #F5F5F5;" |Able to handle daily life activities (including financial issues); judgment good in relation to past performance
| style="padding: 5px 5px; background: #F5F5F5;" | Slight impairment in solving problems, determining similarities and differences
| style="padding: 5px 5px; background: #F5F5F5;" |Mild impairment in solving problems, determining similarities and differences
| style="padding: 5px 5px; background: #F5F5F5;" | Moderate difficulty in solving problems, determining similarities and differences; social judgment usually maintained
| style="padding: 5px 5px; background: #F5F5F5;" |Moderate difficulty in solving problems, difficulty in distinguishing things; social judgment usually maintained
| style="padding: 5px 5px; background: #F5F5F5;" | Severely impaired in solving problems, determining similarities and differences; social judgment usually impaired
| style="padding: 5px 5px; background: #F5F5F5;" |Severely impaired in solving problems, determining similarities and differences; social judgment usually impaired
| style="padding: 5px 5px; background: #F5F5F5;" | Unable to make judgments or solve problems
| style="padding: 5px 5px; background: #F5F5F5;" |Unable to make judgments or solve problems
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Community affairs}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Social functioning}}
| style="padding: 5px 5px; background: #F5F5F5;" | Independent function at usual level in job, shopping, and volunteer and social groups
| style="padding: 5px 5px; background: #F5F5F5;" |Functions independently and performs daily tasks such as shopping, and volunteer and social groups
| style="padding: 5px 5px; background: #F5F5F5;" | Slight impairment in these activities
| style="padding: 5px 5px; background: #F5F5F5;" |Slight impairment in performing social activities
| style="padding: 5px 5px; background: #F5F5F5;" | Unable to function independently at these activities, although may still be engaged in some; appears normal to casual inspection
| style="padding: 5px 5px; background: #F5F5F5;" |Unable to perform social activities, although may still be engaged in some; appears normal on casual observation
| style="padding: 5px 5px; background: #F5F5F5;" | No pretense of independent function outside of home; appears well enough to be taken to functions outside a family home
| style="padding: 5px 5px; background: #F5F5F5;" |No pretense of independent function outside of home; appears well enough to be taken to functions outside a family home
| style="padding: 5px 5px; background: #F5F5F5;" | No pretense of independent function outside of home; appears too ill to be taken to functions outside a family home
| style="padding: 5px 5px; background: #F5F5F5;" |No pretense of independent function outside of home; appears too ill to be taken to functions outside a family home
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" | {{fontcolor|#FFFFFF|Home and hobbies}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Home and hobbies}}
| style="padding: 5px 5px; background: #F5F5F5;" | Life at home, hobbies, and intellectual interests well maintained
| style="padding: 5px 5px; background: #F5F5F5;" |Able to carry out daily life activities, hobbies, and intellectual interests well maintained
| style="padding: 5px 5px; background: #F5F5F5;" | Life at home, hobbies, and intellectual interests slightly impaired  
| style="padding: 5px 5px; background: #F5F5F5;" |Daily life tasks, hobbies, and intellect slightly impaired
| style="padding: 5px 5px; background: #F5F5F5;" | Mild but definite impairment of function at home; more difficult chores abandoned; more complicated hobbies and interests abandoned
| style="padding: 5px 5px; background: #F5F5F5;" |Mild but definite impairment of function in performing daily life tasks; more difficult chores abandoned; more complicated hobbies and interests abandoned
| style="padding: 5px 5px; background: #F5F5F5;" | Only simple chores preserved; interests very restricted and poorly maintained
| style="padding: 5px 5px; background: #F5F5F5;" |Only simple chores preserved; interests very restricted and poorly maintained
| style="padding: 5px 5px; background: #F5F5F5;" | No significant function in home
| style="padding: 5px 5px; background: #F5F5F5;" |No significant function in home
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Personal care}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Personal care}}
| style="padding: 5px 5px; background: #F5F5F5;" | Fully capable of self-care
| style="padding: 5px 5px; background: #F5F5F5;" |Able to take care of self
| style="padding: 5px 5px; background: #F5F5F5;" | Fully capable of self-care
| style="padding: 5px 5px; background: #F5F5F5;" |Fully functional
| style="padding: 5px 5px; background: #F5F5F5;" | Needs prompting
| style="padding: 5px 5px; background: #F5F5F5;" |Needs reminders
| style="padding: 5px 5px; background: #F5F5F5;" | Requires assistance in dressing, hygiene, keeping of personal effects
| style="padding: 5px 5px; background: #F5F5F5;" |Requires assistance in dressing, hygiene, keeping of personal effects
| style="padding: 5px 5px; background: #F5F5F5;" | Requires much help with personal care; frequent incontinence
| style="padding: 5px 5px; background: #F5F5F5;" |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:<ref name="urlAlzheimer Disease Overview - GeneReviews® - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK1161/ |title=Alzheimer Disease Overview - GeneReviews® - NCBI Bookshelf |format= |work= |accessdate=}}</ref><ref name="pmid16966510">{{cite journal |vauthors=Brickell KL, Steinbart EJ, Rumbaugh M, Payami H, Schellenberg GD, Van Deerlin V, Yuan W, Bird TD |title=Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease |journal=Arch. Neurol. |volume=63 |issue=9 |pages=1307–11 |year=2006 |pmid=16966510 |doi=10.1001/archneur.63.9.1307 |url=}}</ref><ref name="pmid10441572">{{cite journal |vauthors=Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, Raux G, Camuzat A, Penet C, Mesnage V, Martinez M, Clerget-Darpoux F, Brice A, Frebourg T |title=Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum |journal=Am. J. Hum. Genet. |volume=65 |issue=3 |pages=664–70 |year=1999 |pmid=10441572 |pmc=1377972 |doi=10.1086/302553 |url=}}</ref><ref name="pmid11216203">{{cite journal |vauthors=Munoz DG, Feldman H |title=Causes of Alzheimer's disease |journal=CMAJ |volume=162 |issue=1 |pages=65–72 |year=2000 |pmid=11216203 |pmc=1232234 |doi= |url=}}</ref><ref name="pmid9848086">{{cite journal |vauthors=Hölscher C |title=Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis |journal=Neurobiol. Dis. |volume=5 |issue=3 |pages=129–41 |year=1998 |pmid=9848086 |doi=10.1006/nbdi.1998.0193 |url=}}</ref>
{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Sub-class'''
! align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Genetics'''
! align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Prevalence'''
|-
| colspan="1" rowspan="1" |'''Late-onset familial (>60 years, AD2)'''
|
*[[APOE]] [[gene]]:
**[[Locus]]: AD2
**[[Protein]]: [[Apolipoprotein E]]
*TREM2 [[gene]]:
**Variant: p.Arg47His [[Allele|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 (<60 years, AD1, AD3, AD4)'''
|
*[[PSEN1]] [[gene]]:
**[[Locus (genetics)|Locus]]: AD3
**Proportion: 20-70 % of early onset AD cases
**[[Protein]]: [[Presenilin 1|Presenilin-1]]
*[[PSEN2]] [[gene]]:
**[[Locus (genetics)|Locus]]: AD4
**Proportion: Rare
**Protein: [[Presenilin|Presenilin-2]]
*[[Amyloid precursor protein|APP]] [[gene]]:
**[[Locus]]: AD1
**Proportion: 10-15 % of early onset AD cases
**[[Protein]]: [[Amyloid precursor protein]] ([[Amyloid precursor protein|APP]])
| colspan="1" rowspan="1" |<2% of [[familial]] cases
|}


*The disease course of Alzheimer's disease is divided into four stages, with a progressive decline in cognition and functional capabilities.
===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
|pmid=11329390
|month=May
|url=http://ajp.psychiatryonline.org/cgi/content/full/158/5/704
|pmid=7733843
|accessdate=2008-08-27
|accessdate=2008-08-04
}}</ref><ref name="pmid12603249">{{cite journal
}}
*{{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 131: Line 137:
|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">
}}</ref><ref name="pmid15703322">{{cite journal
{{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 143: Line 148:
|doi=10.1176/appi.ajgp.13.2.134
|doi=10.1176/appi.ajgp.13.2.134
}}
}}
</ref><ref name="pmid12754679">
</ref><ref name="pmid12754679">{{cite journal
{{cite journal
|author=Spaan PE, Raaijmakers JG, Jonker C
|author=Spaan PE, Raaijmakers JG, Jonker C
|title=Alzheimer's disease versus normal ageing: a review of the efficiency of clinical and experimental memory measures
|title=Alzheimer's disease versus normal ageing: a review of the efficiency of clinical and experimental memory measures
Line 154: Line 158:
|pmid=12754679
|pmid=12754679
}}
}}
</ref>
</ref><ref name="pmid15956265">{{cite journal
[[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
|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 174: Line 177:
|pmid=16567037
|pmid=16567037
|doi=10.1016/j.clineuro.2006.02.003
|doi=10.1016/j.clineuro.2006.02.003
}}</ref><ref name="pmid17485646">
}}</ref><ref name="pmid17485646">{{cite journal
{{cite journal
|author=Palmer K, Berger AK, Monastero R, Winblad B, Bäckman L, Fratiglioni L
|author=Palmer K, Berger AK, Monastero R, Winblad B, Bäckman L, Fratiglioni L
|title=Predictors of progression from mild cognitive impairment to Alzheimer disease
|title=Predictors of progression from mild cognitive impairment to Alzheimer disease
Line 185: Line 187:
|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">
}}</ref><ref name="pmid10653284">{{cite journal
{{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 193: Line 203:
|issue=4
|issue=4
|pages=19–23
|pages=19–23
|year=2007
|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">
}}</ref><ref name="pmid17279076">{{cite journal
{{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 204: Line 211:
|issue=2
|issue=2
|pages=60–1
|pages=60–1
|year=2007
|month=February
|pmid=17279076
|pmid=17279076
|doi=10.1038/ncpneuro0402
|doi=10.1038/ncpneuro0402
}}</ref>
}}</ref><ref name="pmid7967534">{{cite journal
 
|author=Frank EM
===Early dementia===
|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">
|journal=J S C Med Assoc
{{cite journal
|volume=90
|author=Förstl H, Kurz A
|issue=9
|title=Clinical features of Alzheimer's disease
|pages=417–23
|journal=European Archives of Psychiatry and Clinical Neuroscience
|pmid=7967534
|volume=249
}}</ref><ref name="pmid8821346">{{cite journal
|issue=6
|pages=288–290
|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
|author=Jelicic M, Bonebakker AE, Bonke B
|author=Jelicic M, Bonebakker AE, Bonke B
|title=Implicit memory performance of patients with Alzheimer's disease: a brief review
|title=Implicit memory performance of patients with Alzheimer's disease: a brief review
Line 243: Line 231:
|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 270: Line 248:
|issue=4
|issue=4
|pages=441–59
|pages=441–59
|year=1995
|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 280: Line 256:
|issue=4
|issue=4
|pages=715–25
|pages=715–25
|year=1993
|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 296: Line 264:
|issue=1
|issue=1
|pages=19–24
|pages=19–24
|year=2004
|month=March
|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">
}}</ref><ref name="pmid16209425">{{cite journal
{{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 310: Line 275:
|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">
}}</ref><ref>Neuropsychiatric symptoms:
{{cite journal
 
|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 352: Line 284:
|issue=12
|issue=12
|pages=1755–61
|pages=1755–61
|year=2007
|month=December
|pmid=18071039
|pmid=18071039
|doi=10.1001/archneur.64.12.1755
|doi=10.1001/archneur.64.12.1755
Line 364: Line 294:
|issue=5
|issue=5
|pages=438–45
|pages=438–45
|year=2006
|month=May
|pmid=16670248
|pmid=16670248
|doi=10.1097/01.JGP.0000218218.47279.db
|doi=10.1097/01.JGP.0000218218.47279.db
Line 376: Line 304:
|issue=8
|issue=8
|pages=527–32
|pages=527–32
|year=2007
|month=October
|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 387: Line 313:
|issue=3
|issue=3
|pages=171–82
|pages=171–82
|year=2001
|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 397: Line 321:
|issue=1
|issue=1
|pages=10–6
|pages=10–6
|year=1995
|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 425: Line 329:
|issue=6
|issue=6
|pages=650–5
|pages=650–5
|year=1995
|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
|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 435: Line 345:
|issue=5
|issue=5
|pages=637–41
|pages=637–41
|year=1998
|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 455: Line 353:
|issue=1
|issue=1
|pages=59–65
|pages=59–65
|year=1999
|month=July
|pmid=10369823
|pmid=10369823
|pmc=1736445
|pmc=1736445
}}</ref>
}}</ref>
<br clear="left"/>
{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Stage of Alzheime's disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |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
|}


==References==
==References==

Latest revision as of 23:25, 24 September 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2], Aravind Reddy Kothagadi M.B.B.S[3], Haleigh Williams, B.S.

Overview

Alzheimer's disease may be classified according to severity into mild, moderate and severe dementia. It may also be classified based on age of onset into early onset and late onset Alzheimer's disease. Another method of classification of Alzheimer's disease is based on the course of disease into pre-dementia, early dementia, moderate dementia and advanced dementia.

Classification

Classification based on severity

Alzheimer's disease may be classified based on the clinical dementia rating criteria into minimal, intermediate, mild, moderate and severe:[1][2][3][4][5]

Clinical Dementia Rating
Based on the severity of Impairment
Criteria Minimal Indeterminate Mild Moderate Severe
Memory No memory loss or slight forgetfulness Minimal 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 perception Moderate difficulty with time perception; oriented for place at examination; may be disoriented to place 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 Mild impairment in solving problems, determining similarities and differences Moderate difficulty in solving problems, difficulty in distinguishing things; social judgment usually maintained Severely impaired in solving problems, determining similarities and differences; social judgment usually impaired Unable to make judgments or solve problems
Social functioning Functions independently and performs daily tasks such as shopping, and volunteer and social groups Slight impairment in performing social activities Unable to perform social activities, although may still be engaged in some; appears normal on casual observation 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 Able to carry out daily life activities, hobbies, and intellectual interests well maintained Daily life tasks, hobbies, and intellect slightly impaired Mild but definite impairment of function in performing daily life tasks; 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 Able to take care of self Fully functional Needs reminders 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:[6][7][8][9][10]

Sub-class Genetics Prevalence
Late-onset familial (>60 years, AD2) 15%-25% of familial cases
Early-onset familial AD (<60 years, AD1, AD3, AD4) <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:[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][19][27][28][29][30][31][32][33][34][35]

Stage of Alzheime's disease Major deficits
Predementia
Early dementia
Moderate dementia
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

References

  1. ↑ Morris JC (1997). "Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type". Int Psychogeriatr. 9 Suppl 1: 173–6, discussion 177–8. PMID 9447441.
  2. ↑ Berg L (1988). "Clinical Dementia Rating (CDR)". Psychopharmacol Bull. 24 (4): 637–9. PMID 3249765.
  3. ↑ O'Bryant SE, Waring SC, Cullum CM, Hall J, Lacritz L, Massman PJ, Lupo PJ, Reisch JS, Doody R (2008). "Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study". Arch. Neurol. 65 (8): 1091–5. doi:10.1001/archneur.65.8.1091. PMC 3409562. PMID 18695059.
  4. ↑ Morris JC (1993). "The Clinical Dementia Rating (CDR): current version and scoring rules". Neurology. 43 (11): 2412–4. PMID 8232972.
  5. ↑ Morris JC, Ernesto C, Schafer K, Coats M, Leon S, Sano M, Thal LJ, Woodbury P (1997). "Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience". Neurology. 48 (6): 1508–10. PMID 9191756.
  6. ↑ "Alzheimer Disease Overview - GeneReviews® - NCBI Bookshelf".
  7. ↑ Brickell KL, Steinbart EJ, Rumbaugh M, Payami H, Schellenberg GD, Van Deerlin V, Yuan W, Bird TD (2006). "Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease". Arch. Neurol. 63 (9): 1307–11. doi:10.1001/archneur.63.9.1307. PMID 16966510.
  8. ↑ Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, Raux G, Camuzat A, Penet C, Mesnage V, Martinez M, Clerget-Darpoux F, Brice A, Frebourg T (1999). "Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum". Am. J. Hum. Genet. 65 (3): 664–70. doi:10.1086/302553. PMC 1377972. PMID 10441572.
  9. ↑ Munoz DG, Feldman H (2000). "Causes of Alzheimer's disease". CMAJ. 162 (1): 65–72. PMC 1232234. PMID 11216203.
  10. ↑ Hölscher C (1998). "Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis". Neurobiol. Dis. 5 (3): 129–41. doi:10.1006/nbdi.1998.0193. PMID 9848086.
  11. ↑ Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A. "Sundowning and circadian rhythms in Alzheimer's disease". Am J Psychiatry. 158 (5): 704–11. PMID 11329390. Retrieved 2008-08-27.
  12. ↑ 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)
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 19.0 19.1 Förstl H, Kurz A (1999). "Clinical features of Alzheimer's disease". European Archives of Psychiatry and Clinical Neuroscience. 249 (6): 288–290. PMID 10653284.
  20. ↑ Small BJ, Gagnon E, Robinson B. "Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment". Geriatrics. 62 (4): 19–23. PMID 17408315.
  21. ↑ Petersen RC. "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.
  22. ↑ Frank EM. "Effect of Alzheimer's disease on communication function". J S C Med Assoc. 90 (9): 417–23. PMID 7967534.
  23. ↑ 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.
  24. ↑ Becker JT, Overman AA (2002). "[The semantic memory deficit in Alzheimer's disease]". Rev Neurol (in Spanish; Castilian). 35 (8): 777–83. PMID 12402233.
  25. ↑ Hodges JR, Patterson K. "Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications". Neuropsychologia. 33 (4): 441–59. PMID 7617154.
  26. ↑ Benke T. "Two forms of apraxia in Alzheimer's disease". Cortex. 29 (4): 715–25. PMID 8124945.
  27. ↑ Forbes KE, Shanks MF, Venneri A. "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.
  28. ↑ 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.
  29. ↑ Neuropsychiatric symptoms:
    • Scarmeas N, Brandt J, Blacker D; et al. "Disruptive behavior as a predictor in Alzheimer disease". Arch. Neurol. 64 (12): 1755–61. doi:10.1001/archneur.64.12.1755. PMID 18071039.
    • Tatsch MF, Bottino CM, Azevedo D; et al. "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.
    • Volicer L, Bass EA, Luther SL. "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.
  30. ↑ Honig LS, Mayeux R. "Natural history of Alzheimer's disease". Aging (Milano). 13 (3): 171–82. PMID 11442300.
  31. ↑ Gold DP, Reis MF, Markiewicz D, Andres D. "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.
  32. ↑ Souren LE, Franssen EH, Reisberg B. "Contractures and loss of function in patients with Alzheimer's disease". J Am Geriatr Soc. 43 (6): 650–5. PMID 7775724.
  33. ↑ Wada H, Nakajoh K, Satoh-Nakagawa T; et al. "Risk factors of aspiration pneumonia in Alzheimer's disease patients". Gerontology. 47 (5): 271–6. PMID 11490146.
  34. ↑ Berkhout AM, Cools HJ, van Houwelingen HC. "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.
  35. ↑ Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R. "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.

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