History and exam

Your Organizational Guidance

ebpracticenet urges you to prioritize the following organizational guidance:

Guide de pratique clinique pluridisciplinaire relatif à la collaboration dans la dispense de soins aux personnes âgées démentes résidant à domicile et leurs aidants prochesPublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2017Multidisciplinaire richtlijn voor thuiswonende oudere personen met dementie en hun mantelzorgersPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2017

Key diagnostic factors

common

memory loss

The hallmark feature of Alzheimer disease is memory decline, with loss of recent memory first. Symptoms progress, with new information rapidly lost, and later, only fragments of memory remaining.

disorientation

Disorientation to time and place. Subtle at first; may manifest behaviorally as misplacing items or getting lost.

nominal dysphasia

Difficulties naming objects/people. Assessed in the Mini-Mental State Examination. Proper names and low-frequency words decline first.

misplacing items/getting lost

May be initial presenting symptom and may be due to memory disorientation or visuospatial dysfunction.

apathy

May become passive, sleep more than usual, or not want to perform usual activities.

decline in activities of daily living and instrumental activities of daily living (IADLs)

Some people are able to remain physically functional long into the disease process. The earliest deficits are in performing IADLs, such as cooking and shopping. This may be due to memory and/or executive function difficulties. Later in Alzheimer disease, continence, ability to dress and groom, and eventually, ambulation and verbalization may be lost.

personality change

Subtle changes develop in personality, and diminished interest in usual activities may be evident.

unremarkable initial physical exam

Physical exam is mostly unremarkable in early stages. In advanced disease patients tend to appear sloppily dressed, confused, apathetic, and disorientated with a slow, shuffling gait and stooped posture. Terminal disease is marked by rigidity and inability to walk and speak.

Other diagnostic factors

common

mood and behavior changes

Some people with Alzheimer disease may become depressed, apathetic, agitated, and/or irritable. Aggression, disinhibition, paranoia, delusions, hallucinations, and sundowning (behavior change at dusk) may become evident.[93][94]

poor abstract thinking

Complex tasks requiring organization and planning become difficult.

constructional dyspraxia

Parietal lobe deficits may lead to difficulties completing the clock-drawing test or intersecting pentagons in the Mini-Mental State Examination.

uncommon

prosopagnosia

Failure to recognize familiar faces.

autoprosopagnosia

Failure to recognize oneself in the mirror. More common late in the illness.

Risk factors

strong

advanced age

Numerous studies have shown that the risk of Alzheimer disease (AD) increases with advancing age. Age is considered the major risk factor in incidence of AD.

Above the age of 65 years, AD incidence doubles every 5 years.[43]

family history

The estimated lifetime risk of Alzheimer disease (AD) in first-degree relatives without a defined underlying genetic risk factor for AD is 25% to 50%.[44][45]

genetics

Around 70% of Alzheimer disease (AD) risk is thought to be due to genetic factors.[16]

Mutations in three genes - presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) - are associated with early onset familial cases of AD.[16][46]​​

The APOE e4 allele contributes to sporadic cases of late-onset AD, whereas the APOE e2 isoform is protective.[47][48]​​ One genome-wide association study identified 75 risk loci for AD and related dementias, but although many polymorphisms have been explored in AD, none are used predictively.[46][49]​​​​

Down syndrome

Trisomy 21 resulting in Down syndrome is associated with the development of amyloid plaques in the brain. Rate of deposition increases markedly between 35 and 45 years of age.

Clinical signs and symptoms of Alzheimer disease develop in some people with Down syndrome from around age 50 years, and are observed in around 75% of people with Down syndrome over age 60 years.[50]

cerebrovascular disease

Cerebrovascular disease is a strong risk factor for vascular dementia, which sometimes coexists with Alzheimer disease (mixed dementia). Up to one third of patients with stroke develop dementia within 5 years.[51]

Incident atrial fibrillation has been shown to be a risk factor for dementia in older people, even in the absence of stroke.[52]​​

lifestyle factors and environment

Smoking, midlife obesity, a diet high in saturated fats, abstinence from alcohol in midlife, sedentary lifestyle, and consumption of more than 14 units of alcohol per week have been associated with an increased risk for the development of Alzheimer disease (AD) and all-cause dementia.​[20][21]​​​​​[22][23][24]​​​​​ Moderate alcohol consumption (1-14 units/week) may protect against dementia.[21]​​​​[22]

Modifiable risk factors associated with the greatest increased risk for dementia include smoking in midlife, hypertension and prehypertension, and diabetes (although some studies suggest that type 2 diabetes is associated with an increased risk of vascular dementia, but not of AD).[21]​​​[53][54]

Several studies suggest that exposure to particulate air pollution increases the risk of dementia or cognitive decline.[55][56]​​

use of certain drugs

Some drugs (e.g., anticholinergic drugs; androgen deprivation therapy in men with prostate cancer) have been associated with increased risk of Alzheimer disease (AD), but it is unclear whether this is the direct effect of the drugs themselves or is related to the underlying medical conditions and/or related lifestyle factors.[36][37][38]​​ Some studies have suggested that long-term use of postmenopausal hormone replacement therapy in women may be associated with increased risk of AD, but the evidence is inconsistent.[57][58][59]

less than high school education

Less than high school education has been associated with a greater risk of developing all-cause dementia.[21]​​​​[60]​ Other measures of deprivation have also been implicated, and studies into these aspects are ongoing.[61]

weak

traumatic brain injury

Even mild injury without loss of consciousness increases the risk of developing Alzheimer disease. The more severe the traumatic brain injury, the higher the risk.[21]​​​[26]​ 

depression

Increases the risk of developing Alzheimer disease (AD).​​​ It is unclear whether depression represents a true risk factor or a prodrome of AD.[21]​​​[62][63]​​​​

hearing loss

Age-related hearing loss is associated with cognitive decline and all-cause dementia.[21]​​​[27][28]

periodontal disease

Systematic reviews suggest that periodontal disease is associated with an elevated risk of Alzheimer disease and cognitive impairment. Further well-designed studies are needed to investigate this link.[32][33]

visual impairment

Visual impairment has been suggested to be associated with an increased risk of all-cause dementia. Further studies are needed that include objectively measured visual impairment (as opposed to self-reported survey data).[34][35]

herpes simplex virus type 1 (HSV-1) infection

Meta-analysis has suggested that HSV-1 infection is a risk factor for Alzheimer disease.[64]

hyperlipidemia

Hyperlipidemia is a weak risk factor for vascular dementia (which sometimes coexists with Alzheimer disease [mixed dementia]).[65][66]

female sex

Alzheimer disease is more common in women than in men.[7]​​[10]

elevated plasma homocysteine level

It is not clear whether homocysteine is a proxy marker for an underlying metabolic process or an etiologic factor in its own right; however, elevated homocysteine is certainly associated with increased dementia risk.[30][67]​​[68]

surgery under general anesthesia

Meta-analysis has demonstrated a significant positive association between general anesthesia and Alzheimer disease. However, it was not possible to discriminate the influence of general anesthesia from the effect of surgery itself; further studies are needed.[69]​ Small studies of anesthesia without surgery have not confirmed the effect of anesthesia on cognition.[70]

Use of this content is subject to our disclaimer