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DEMENTIA

Umer Farooq, MD Saeed Ahmed, MD

BASICS

DESCRIPTION

DSM-5 classifies dementias under neurocognitive disorders (major and mild).

Evidence of cognitive decline from previous level of performance in one of cognitive domains (attention, executive function, learning, and memory). The cognitive deficits interfere significantly with ADLs (for major only) and do not occur exclusively in the context of delirium or any other mental disorder. DSM-5 specifies the cause of neurocognitive decline secondary to the following:

–Alzheimer dementia (AD)

Progressive cognitive decline; most common age >65 years

–Vascular dementia (VaD)

Usually correlated with a cerebrovascular event and/or cerebrovascular disease

Stepwise deterioration with periods of clinical plateaus

–Lewy body dementia

Fluctuating cognition associated with parkinsonism, hallucinations and delusions, gait difficulties, and falls

–Frontotemporal dementia

Language difficulties, personality changes, and behavioral disturbances

–Creutzfeldt-Jakob disease (CJD) Very rare; rapid onset

–HIV dementia

–Substance-/medication-induced neurocognitive disorder

EPIDEMIOLOGY

Prevalence

In patients age ≥71 years

–AD: 5–10% up to 25% after 7th decade of life

–VaD: 17%

–Other: 13%

Estimated 5.4 million Americans had AD in 2010.

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–5 million >65 years of age; 200,000 <65 years

–Prevalence expected to double by 2030.

ETIOLOGYAND PATHOPHYSIOLOGY

AD: involves β-amyloid protein accumulation and/or neurofibrillary tangles (NFTs), synaptic dysfunction, neurodegeneration, and eventual neuronal loss

Age, genetics, systemic disease, smoking, and other host factors may influence the β-amyloid accumulation and/or the pace of progression toward the clinical manifestations of AD.

VaD: cerebral atherosclerosis/emboli with clinical/subclinical infarcts

Genetics

AD: Positive family history in 50%, but 90% AD is sporadic: APOE4 increases risk but full role unclear.

Familial/autosomal dominant AD accounts for <5% AD: amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2).

RISK FACTORS

Age; sex: female > male

Genetic predisposition

Hypertension: AD; VaD

Hypercholesterolemia: AD; VaD

Diabetes: VaD

Cigarette smoking: VaD

Endocrine/metabolic abnormalities: hypothyroidism, Cushing syndrome; thiamine and vitamin B12 deficiency

Chronic alcoholism, other drugs

Lower educational status

Head injury early in life

Sedentary lifestyle

GENERALPREVENTION

Treat reversible causes of dementia, such as drug-induced, alcohol-induced, and vitamin deficiencies.

Treat hypertension, hypercholesterolemia, and diabetes.

No evidence for statins (or any other specific medication) to prevent onset of dementia (1)[A]

BPcontrol and low-dose aspirin may prevent or lessen cognitive decline in

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VaD.

COMMONLYASSOCIATED CONDITIONS

Anxiety and major depression

Psychosis (delusions; delusions of persecution are common)

Delirium

Behavioral disturbances (agitation, aggression) Sleep disturbances

DIAGNOSIS

HISTORY

Probable diagnosis AD (2)[B]:

Age between 40 and 90 years (usually >65 years)

Progressive cognitive decline of insidious onset

No disturbances of consciousness

Deficits in areas of cognition

No other explainable cause of symptoms

Specifically rule out thyroid disease, vitamin deficiency (B12), grief reaction,

and depression.

Supportive factors: family history of dementia

PHYSICALEXAM

Often normal physical

No disturbances of consciousness

Cognitive decline demonstrated by standardized instruments, including the following:

–Mini-Mental State Examination

–Montreal Cognitive Assessment (MoCA) test

–ADAS-Cog

–Clock draw test

–Use caution in relying solely on cognition scores, especially in those with learning difficulty, language barriers, or similar limitations.

DIFFERENTIALDIAGNOSIS

Major depression

Medication side effect

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Chronic alcohol use

Delirium

Subdural hematoma

Normal pressure hydrocephalus

Brain tumor

Thyroid disease

Parkinson disease

Vitamin B12 deficiency

Toxins (aromatic hydrocarbons, solvents, heavy metals, marijuana, opiates, sedative-hypnotics)

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Used to rule out causes

–CBC, CMP

–Thyroid-stimulating hormone

–Vitamin B12 level

Select patients

–HIV, rapid plasma regain (RPR)

–Erythrocyte sedimentation rate (ESR)

–Folate

–Heavy metal and toxicology screen

Research studies with cerebrospinal fluid (CSF) biomarkers in patient with confirmed AD have shown decreased Abeta (1 to 42) and increased tau and p-tau levels, which are specific features of AD, and CSF tau proteins are increased in CJD (3)[A].

Neuroimaging (CT/MRI of brain): cerebral atrophy

–Early age of onset (<65 years), rapid progression, focal neurologic deficits, cerebrovascular disease risk, or atypical symptoms: neuroimaging (MRI/CT) to rule out other causes

–Important findings

AD: diffuse cerebral atrophy starting in association areas, hippocampus, amygdala

VaD: old infarcts, including lacunar

Diagnostic Procedures/Other

PET scan not routinely recommended; has been approved to differentiate between Alzheimer disease and frontotemporal dementia

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Test Interpretation

AD

NFTs: abnormally phosphorylated tau protein

Senile plaques: APP derivatives

Microvascular amyloid

TREATMENT

GENERALMEASURES

Daily schedules and written directions

Emphasis on nutrition, personal hygiene, accident-proofing the home, safety issues, sleep hygiene, and supervision

Socialization (adult daycare)

Sensory stimulation (display of clocks and calendars) in the early to middle stages

Discussion with the family concerning support and advance directives

MEDICATION

Cognitive dysfunction

Medications for AD (4)[A] show a small improvement in some cognitive measures, but it remains unclear if the improvement is clinically significant. Cognitive dysfunction, mild

–Cholinesterase inhibitors: donepezil (Aricept), 5 to 10 mg/day; rivastigmine (Exelon), 1.5 to 6 mg BID, transdermal system 4.6 mg/24 hours and 9.5 mg/24 hours; galantamine (Razadyne), 4 to 12 mg BID, extended release 8 to 24 mg/day

Adverse events: nausea, vomiting, diarrhea, anorexia, nightmares, bradycardia/syncope

Galantamine warning: associated with mortality in patients with mild cognitive impairment in clinical trial

It is suggested to consider cholinesterase inhibitor for patients with mild to moderate dementia (MMSE 10 to 26).

The patients with moderate to advanced dementia (MMSE <17), recommendations are to add memantine (10 mg twice daily) to a cholinesterase inhibitor, or using memantine alone in patients who do not tolerate or benefit from a cholinesterase inhibitor.

In patients with severe dementia (MMSE <10), it is suggested continuing

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memantine. However, in advanced dementia, medications can be discontinued to maximize quality of life and patient comfort.

Start drug with lowest acquisition cost; also consider adverse event profile, adherence, medical comorbidity, drug interactions, and dosing profiles.

Cognitive dysfunction, moderate to severe

–Cholinesterase inhibitors OR

–Memantine (Namenda), 5 to 20 mg/day

Adverse events: dizziness, confusion, headache, constipation

OR combination cholinesterase inhibitor and memantine Commonly associated conditions

–Psychosis and agitation/aggressive behavior:

Look for precipitating factors (infection, pain, depression, medications).

Nonpharmacologic therapies (behavioral interventions, music therapy, etc.) are preferred as first-line treatment.

Mood stabilizers (valproic acid, carbamazepine) have been used although evidence is lacking.

For moderate/severe symptoms; antipsychotics: Initiate low doses,

risperidone 0.25 to 1 mg/day; olanzapine 1.25 to 5 mg/day; quetiapine 12.5 to 50 mg/day; aripiprazole 5 mg/day; ziprasidone 20 mg/day

Atypical antipsychotics associated with a better side effect profile: quetiapine and aripiprazole often first line due to decreased extrapyramidal side effect

ALERT

Black box warning on antipsychotics due to increased mortality in elderly with dementia

Depression and insomnia

–Depression:

Selective serotonin reuptake inhibitors (SSRIs): Initiate low doses, citalopram (Celexa) 10 mg/day; escitalopram (Lexapro) 5 mg/day; sertraline (Zoloft) 25 mg/day.

Adverse events: nausea, vomiting, agitation, parkinsonian effects, sexual dysfunction, hyponatremia

Venlafaxine, mirtazapine, and bupropion are also useful.

–Sleep disturbances:

Low-dose antidepressants (e.g., Remeron) have significant sedative properties at 7.5 or 15 mg.

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Trazodone 25 to 100 mg is frequently used because of better side effect profile.

–Psychosis and agitation/aggressive behavior: Some data for SSRIs

Benzodiazepines if agitation with anxiety; in elderly, use PRN.

Geriatric Considerations

Initiate pharmacotherapy at low doses and titrate slowly up if necessary.

Benzodiazepines are potentially inappropriate for older adults, yet their use persists.

ALERT

Benzodiazepine use is associated with increased fall risk (5)[B]. Watch decreased renal function and hepatic metabolism.

ISSUES FOR REFERRAL

Neuropsychiatric evaluation particularly helpful in early stages or mild cognitive impairment

ADDITIONALTHERAPIES

Behavioral modification

Socialization, such as adult daycare, to prevent isolation and depression

Sleep hygiene program as alternative to pharmaceuticals for sleep disturbance

Scheduled toileting to prevent incontinence

COMPLEMENTARY& ALTERNATIVE MEDICINE

Vitamin E is no longer recommended due to lack of evidence.

Ginkgo biloba is not recommended due to lack of evidence.

NSAIDs, selegiline, and estrogen lack efficacy and safety data.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Worsening physical health issues

Psychiatry admission may be required because of safety concerns (selfharm/harm to others), self-neglect, aggressive behaviors, or other behavioral issues.

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ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

Progression of cognitive impairment by use of standardized tool (e.g., MMSE, ADAS-Cog)

Development of behavioral problems: sleep, depression, psychosis

Adverse events of pharmacotherapy

Nutritional status

Caregiver evaluation of stress

PATIENT EDUCATION

Long-term issues: safety, management of finances, medical decision making, possible placement; legal guardianship, if necessary

Advance directives

National Institute on Aging. About Alzheimer’s disease: other dementias: http://www.nia.nih.gov/alzheimers/topics/other-dementias

PROGNOSIS

AD: usually steady progression leading to profound cognitive impairment:

– Average survival of AD is about 8 years.

VaD: incrementally worsening dementia, but cognitive improvement is unlikely

Secondary dementias: Treatment of the underlying condition may lead to improvement; commonly seen with normal pressure hydrocephalus, hypothyroidism, and brain tumors

COMPLICATIONS

Wandering

Delirium

Sundowner syndrome is common in older people (who are sedated) and also in people who have dementia (adverse reaction to small dose of psychoactive substances).

Falls with injury

–Hip fracture

–Head trauma/hematomas

Neglect and abuse

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Caregiver burnout

REFERENCES

1.McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2009;(2):CD003160.

2.Blass DM, Rabins PV. In the clinic. Dementia. Ann Intern Med. 2008;148(7):ITC4-1–ITC4-16.

3.van Harten AC, Kester MI, Visser PJ, et al. Tau and p-tau as CSF biomarkers in dementia: a meta-analysis. Clin Chem Lab Med. 2011;49(3):353–366.

4.Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593.

5.Softic A, Beganlic A, Pranjic N, et al. The influence of the use of benzodiazepines in the frequency falls in the elderly. Med Arch. 2013;67(4):256–259.

ADDITIONALREADING

Lyketsos CG, Colenda CC, Beck C, et al. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer disease. Am J Geriatr Psychiatry.

2006;14(7):561–572.

National Collaborating Centre for Mental Health. Dementia: A NICE-SCIE Guideline on Supporting People with Dementia and Their Carers in Health and Social Care. NICE Clinical Guidelines, no. 42. London, United Kingdom: British Psychological Society, Royal College of Psychiatrists; 2007. http://www.nice.org.uk/nicemedia/live/10998/30320/30320/pdf. Accessed November 14, 2017.

Rabins PV, Blacker D, Rovner BW, et al; and APAWork Group on Alzheimer’s Disease and Other Dementias. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry. 2007;164(Suppl 12):5–56.

SEE ALSO

Algorithm: Dementia

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