May 2019 By PsychDB.com

Alzheimer's Disease (AD)

Alzheimer's Disease is the most common type of dementia in the world, characterized by progressive memory loss and behavioural changes.

Prevalence

In developed countries, dementia rates begin at 5-10% for individuals in the seventh decade of life, increasing to 25% thereafter. The percentage of dementias due to Alzheimer's disease is at least 50% (with some estimates suggesting 60-90%).

Course

The onset of symptoms is usually in the eighth and ninth decades of life. Patients with early onset symptoms in their 50s/60s usually have a genetic cause. The mean survival time is 10 years. During the later stages of illness, patients can become mute or bedbound. Death most commonly results from aspiration in those who survive through throughout the course of illness.

The head-turning sign can be a useful sign in the interview of patients suspected of having AD.[1][2]
Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

There is insidious onset and gradual progression of impairment in 1 or more cognitive domains (for major neurocognitive disorder, at least 2 domains must be impaired).

Criterion C

Criteria are met for either probable or possible Alzheimer’s disease as follows:

For Major Neurocognitive Disorder

Probable Alzheimer’s Disease is diagnosed if either of the following is present; otherwise, Possible Alzheimer’s Disease should be diagnosed.

  1. Evidence of a causative Alzheimer’s disease genetic mutation from family history or genetic testing.
  2. All 3 of the following are present:
    • a. Clear evidence of decline in memory and learning AND at least 1 other cognitive domain (based on detailed history or serial neuropsychological testing).
    • b. Steadily progressive, gradual decline in cognition, without extended plateaus.
    • c. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).
For Mild Neurocognitive Disorder

Probable Alzheimer’s disease is diagnosed if there is evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history.

Possible Alzheimer’s disease is diagnosed if there is no evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history, and all 3 of the following are present:

  1. Clear evidence of decline in memory and learning
  2. Steadily progressive, gradual decline in cognition, without extended plateaus
  3. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely contributing to cognitive decline).
Criterion D

The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

In 2011, the National Institute on Aging (NIA) at National Institutes of Health (NIH) and the Alzheimer's Association (AA) published the latest guidelines (NIA-AA) for the diagnosis of Alzheimer's disease.[3] This diagnostic framework continues to be revised as of 2018.[4]

Probable

Diagnostic Criteria

McKhann, Guy M., et al. Recommendations from the NIA-AA workgroup. Alzheimer's and dementia 7.3 (2011)263-269.
Criteria for all-cause dementia
1. Interfere with the ability to function at work or at usual activities; and
2. Represent a decline from previous levels of functioning and performing; and
3. Are not explained by delirium or major psychiatric disorder;
4. Cognitive impairment is detected and diagnosed through a combination of (1) history-taking from the patient and a knowledgeable informant and (2) an objective cognitive assessment, either a “bedside” mental status examination or neuropsychological testing. Neuropsychological testing should be performed when the routine history and bedside mental status examination cannot provide a confident diagnosis.
5. The cognitive or behavioural impairment involves a minimum of two of the following domains:

• Impaired ability to acquire and remember new information (repetitive questions or conversations, misplacing personal belongings, forgetting events or appointments, getting lost on a familiar route).

• Impaired reasoning and handling of complex tasks, poor judgment (poor understanding of safety risks, inability to manage finances, poor decision-making ability, inability to plan complex or sequential activities).

• Impaired visuospatial abilities (inability to recognize faces or common objects or to find objects in direct view despite good acuity, inability to operate simple implements, or orient clothing to the body).

• Impaired language functions (speaking, reading, writing problems - difficulty thinking of common words while speaking, hesitations; speech, spelling, and writing errors).

• Changes in personality, behaviour, or comportment (uncharacteristic mood fluctuations such as agitation, impaired motivation, initiative, apathy, loss of drive, social withdrawal, decreased interest in previous activities, loss of empathy, compulsive or obsessive behaviours, socially unacceptable behaviours).

Probable Alzheimer's

Core clinical criteria
Meets criteria for dementia described earlier in the text, and in addition, has the following characteristics (A to D):
A. Insidious onset. Symptoms have a gradual onset over months to years, not sudden over hours or days;
B. Clear-cut history of worsening of cognition by report or observation; and
C. The initial and most prominent cognitive deficits are evident on history and examination in 1 of the following categories.

a. Amnestic presentation: It is the most common syndromic presentation of AD dementia. The deficits should include impairment in learning and recall of recently learned information. There should also be evidence of cognitive dysfunction in at least 1 other cognitive domain, as defined earlier in the text.

b. Nonamnestic presentations:
• Language presentation: word-finding deficits, but deficits in other cognitive domains should be present.
• Visuospatial presentation: spatial cognition deficits, including object agnosia, impaired face recognition, simultanagnosia, and alexia. Deficits in other cognitive domains should be present.
• Executive dysfunction: deficits of impaired reasoning, judgment, and problem solving. Deficits in other cognitive domains should be present.
D. The diagnosis of probable AD dementia SHOULD NOT be applied when there is evidence of:

a. Substantial concomitant cerebrovascular disease, defined by a history of a stroke temporally related to the onset or worsening of cognitive impairment; or the presence of multiple or extensive infarcts or severe white matter hyperintensity burden; or
b. Core features of Dementia with Lewy bodies other than dementia itself; or
c. Prominent features of behavioural variant frontotemporal dementia; or
d. Prominent features of semantic variant primary progressive aphasia or nonfluent/agrammatic variant primary progressive aphasia; or
e. Evidence for another concurrent, active neurological disease, or a non-neurological medical comorbidity or use of medication that could have a substantial effect on cognition.

Probable AD dementia with increased level of certainty

This certainty specifier can be used if one of the criteria below are met
Criteria
Probable AD dementia with documented decline In persons who meet the core clinical criteria for probable AD dementia, documented cognitive decline increases the certainty that the condition represents an active, evolving pathologic process, but it does not specifically increase the certainty that the process is that of AD pathophysiology. Probable AD dementia with documented decline is defined as follows: evidence of progressive cognitive decline on subsequent evaluations based on information from informants and cognitive testing in the context of either formal neuropsychological evaluation or standardized mental status examinations.
Probable AD dementia in a carrier of a causative AD genetic mutation In persons who meet the core clinical criteria for probable AD dementia, evidence of a causative genetic mutation (in APP, PSEN1, or PSEN2), increases the certainty that the condition is caused by AD pathology. The workgroup noted that carriage of the ε4 allele of the apolipoprotein E gene was not sufficiently specific to be considered in this category.

Possible

Possible AD dementia: Core clinical criteria

Criteria
Atypical course Atypical course meets the core clinical criteria in terms of the nature of the cognitive deficits for AD dementia, but either has a sudden onset of cognitive impairment or demonstrates insufficient historical detail or objective cognitive documentation of progressive decline,
Etiologically mixed presentation Etiologically mixed presentation meets all core clinical criteria for AD dementia but has evidence of:
a. concomitant cerebrovascular disease, defined by a history of stroke temporally related to the onset or worsening of cognitive impairment; or the presence of multiple or extensive infarcts or severe white matter hyperintensity burden; or
b. features of Dementia with Lewy bodies other than the dementia itself; or
c. evidence for another neurological disease or a non-neurological medical comorbidity or medication use that could have a substantial effect on cognition

Individuals with Alzheimer's disease (AD) may have executive dysfunction, language impairment, and/or behavioural changes early in the disease, this can make it challenging to differentiate from frontotemporal dementia.[5]

The amyloid cascade hypothesis and the tau hypothesis are the two predominant theories behind the pathogenesis of AD. Both amyloid plaques and neurofibrillary tangles are found in post-mortem pathology. Individuals with polymorphism in apolipoprotein E4 have an increased risk of AD and earlier age of onset, particularly in homozygous individuals. Increasing links are being found between the pathophysiology of Alzheimer's and hyperglycemia.[6] Hypertension in lafe-life is also a risk factor for development of Alzhemier's pathology.[7]

The differential diagnosis for Alzheimer's disease is broad, as it overlaps with other neurodegenerative disorders. In older adults, it is particularly important to rule out primary psychiatric disorders (depression in particular) which can mimic dementia.

The diagnosis of Alzheimer's Disease remains a clinical diagnosis, though neuroimaging and biomarkers are beginning to play a larger role in diagnosis. Amyloid-based diagnostic tests such as amyloid imaging on brain positron emission tomography (PET) scans and measuring amyloid beta-42 (look for reduced levels) in the cerebrospinal fluid (CSF) may sometimes be helpful. Signs of neuronal injury, such as hippocampal and temporoparietal cortical atrophy on a MRI or temporoparietal hypometabolism on a fluorodeoxyglucose PET scan may provide non-specific evidence for AD.

Current treatments do not alter the course of the disease. Medications only serve to reduce the rate of decline, and symptomatic improvement.

Caregivers

It is extremely important for education about the illness to be provided to both the patient and their families. Caregiver support is also extremely important as the disease progresses. Better caregiver support and interventions helps delay institutionalization.[8]

Dementia

  • Acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) as a class are modestly efficacious for mild to moderate AD, and a trial of these medications is recommended for most patients diagnosed with AD.
  • Memantine monotherapy is another treatment option for patients with moderate to severe stages of AD. Use of memantine in mild AD is not recommended.
  • There is insufficient evidence to recommend for or against the combination treatment with an acetylcholinesterase inhibitor and memantine.[9]

Depression

If the patient had an inadequate response to the nonpharmacological interventions or has a major affective disorder, severe dysthymia or severe emotional lability, a trial of an antidepressant could be considered.[10]