Alzheimer Disease Differential Diagnoses

Updated: Jul 07, 2023
  • Author: Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Diagnostic Considerations


Depression is an important consideration in the differential diagnosis of Alzheimer disease (AD). The clinical manifestations of depression overlap with those of AD. The term pseudodementia refers to the appearence of cognitive dysfunction (dementia) due to depression. In addition, an estimated 30–50% of AD patients have comorbid depression. [74]

Depression in patients with AD appears to differ from depression in cognitively intact elderly patients. Depression in AD more often features motivational disturbances (eg, fatigue, psychomotor slowing, apathy), whereas depression in geriatric patients without cognitive impairment tends to feature mood symptoms (eg, depressed mood, anxiety, suicidality, sleep and appetite disturbances). [74]

Commonly used instruments for assessing depression (eg, Hamilton Scale for Depression, Beck Depression Inventory, Geriatric Depression Scale) were designed for use in other patient populations and may be less reliable in patients with AD. Consequently, the National Institute of Mental Health has developed provisional diagnostic criteria for depression in AD. [74]

Chronic traumatic encephalopathy

Repetitive head trauma has long been recognized as a cause of brain degeneration in boxers (ie, dementia pugilistica). More recently, progressive degenerative brain disease (chronic traumatic encephalopathy [CTE]) has been recognized in athletes with a history of multiple concussions, as well as milder blows to the head that do not cause concussion. [75] Neuropathologically confirmed CTE has been reported in retired professional football and hockey players and other athletes with a history of repeated head injuries.

Pathological hallmarks of CTE, which may not appear until long after the end of active athletic involvement, include the following [76] :

  • Tau-positive neurofibrillary tangles (NFTs) in the neocortex, concentrated around penetrating parenchymal vessels

  • Neuropil threads

  • Neocortical diffuse amyloid plaques, with or without neuritic plaques

  • Sparing of the hippocampus

The distribution of NFTs in CTE differs markedly from that in normal aging and AD, in which there is early involvement of the entorhinal cortex and hippocampus with later involvement of the neocortex in advanced stages.

The symptoms of CTE may include the following [76] :

  • Recurrent headaches

  • Dizziness

  • Mood disorders

  • Aggression

  • Impaired judgment and impulse control

  • Parkinsonian movement disorders

  • Progressive dementia

For more information, see the Medscape Reference article Repetitive Head Injury Syndrome.

Other disorders

Other disorders to consider in the differential diagnosis of AD include the following:

  • Age-associated memory impairment

  • Alcohol or drug abuse

  • Depression

  • Vitamin B12 deficiency

  • Cerebrovascular disease (and vascular dementia)

  • Hearing or visual impairment

  • Hypernatremia

  • Hypoglycemia

  • Hypothyroidism or hyperthyroidism

  • Lewy body dementia

  • Normal pressure hydrocephalus

  • Parkinson's disease with dementia

  • Polypharmacy

  • Volume depletion

  • Wernicke-Korsakoff Syndrome

Differential Diagnoses