Alzheimer’s Disease and Mild Cognitive Impairment

General Considerations

• 1.

  How is dementia defined? How do definitions vary?

  Dementia is generally regarded as an acquired loss of cognitive function due to an abnormal brain condition. The National Institutes of Health criteria (formerly the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer’s Disease and Related Disorders Association or NINCDS-ADRDA criteria) for the diagnosis of Alzheimer’s disease (AD) stressed that there must be progressive loss of cognitive function, including but not limited to memory loss. A recent revision of these criteria puts less emphasis on memory impairment. The DSM-IV general criteria for dementia included the requirement of functional decline that interferes with work or usual social activities in addition to cognitive decline. DSM-5 now calls this major neurocognitive disorder instead of dementia .

• 2.

  What is senility? Is it normal?

  Senility is an outdated term. It used to mean cognitive impairment due to aging, which was assumed to be normal. Although memory, learning, and thinking change with age in subtle ways, memory loss and cognitive impairment are not features of normal aging.

• 3.

  What is pseudodementia?

  Pseudodementia has many meanings. It refers to depressed patients who are cognitively impaired and often have psychomotor slowing but do not have one of the well-defined dementia syndromes. The term does not mean that the patient is consciously simulating dementia (malingering) or is cognitively intact but believes himself or herself to be demented (Ganser’s syndrome). Some researchers believe that pseudodementia may be a precursor to dementia.

• 4.

  What features are characteristic of pseudodementia associated with depression?

  Patients with pseudodementia may or may not have a history of depressive or vegetative symptoms. They tend to have flat affect, to give up easily when mental status is examined, or to say that they cannot perform a task without even trying it. They often respond surprisingly well when given extra time and encouragement, but they may deny their success. Results of mental status examination are inconsistent; for example, they may fail a simple task but perform a similar, more difficult one correctly. Or they may have variable strengths and weaknesses over repeated testing sessions.

• 5.

  What is Ganser’s syndrome?

  Ganser’s syndrome is an involuntary and unconscious simulation of altered mental status (confusion or dementia) in a patient who is not malingering and believes in the validity of his or her symptoms.

• 6.

  What is delirium?

  Delirium is an acute confusional state.

• 7.

  What features distinguish delirium from dementia?

  Although this distinction cannot always be made with certainty, several features are helpful. Sudden onset suggests delirium, as do findings of altered consciousness, marked problems with attention and concentration out of proportion to other deficits, cognitive fluctuations (e.g., lucid intervals), psychomotor and/or autonomic overactivity, fragmented speech, and marked hallucinations (especially auditory or tactile). Chronically demented patients may develop delirium in addition to dementia, which will change the clinical picture.

• 8.

  Do all patients with dementia develop psychotic features?

  No. Psychosis is a variable finding in all types of dementias and is not even clearly related to the stage or severity of dementia.

  American Psychiatric Association: Diagnostic and statistical manual of mental disorders , ed 5. Washington, DC: American Psychiatric Association, 2013.

  McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr., Kawas CH, et al.: The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):263-269, 2011.

• 9.

  Which screening instruments are commonly used in detecting dementia?

  The Folstein Mini-Mental Status Examination (MMSE), Short Blessed Dementia Scale, and Mattis Dementia Rating Scale are commonly used clinically and in experimental studies to screen for dementia and to rate severity of dementia. Recently, the AD8 and Mini-Cog have also been suggested, especially in primary care practices conducting the Annual Wellness Examination.

• 10.

  What are the limitations of the MMSE in the assessment of dementia?

  Besides the fact that it has both false-positive (usually depression) and false-negative (usually early dementia in highly functioning patients) results, the MMSE also has limitations based on its lack of comprehensiveness.

• 11.

  At what point is a patient too demented to require an evaluation?

  No patient is too demented to be evaluated. The need to rule out reversible causes and structural lesions always remains. Neurologic and psychometric examinations can be tailored to the level of even the most profoundly demented patients. Further, even severely demented patients may respond to treatments.

• 12.

  What are the most common causes of dementia or conditions resembling dementia?

  AD is the most common form of dementia in adults (>80% in most series). Depression with pseudodementia is a frequent cause of cognitive loss and must be ruled out in all patients. Other important causes include multi-infarct or vascular dementia, dementia with Lewy bodies, frontotemporal dementia, and dementia-like syndromes due to alcohol or chronic use of certain prescription drugs.

• 13.

  What uncommon causes of dementia must be considered in the differential diagnosis of every patient with dementia ?

  • Toxins (lead, organic mercury)

  • Vitamin deficiencies (B12, B1, and B6, in particular)

  • Endocrine disturbances (hypothyroidism or hyperthyroidism, hyperparathyroidism, Cushing’s disease, and Addison’s disease)

  • Chronic metabolic conditions (hyponatremia, hypercalcemia, chronic hepatic failure, and renal failure)

  • Vasculopathies affecting the brain

  • Structural abnormalities (chronic subdural hematomas, normal pressure hydrocephalus, and slow-growing tumors)

  • Central nervous system (CNS) infections (including human immunodeficiency virus [HIV]), Creutzfeldt–Jakob disease, and cryptococcal or tuberculous meningitis

• 14.

  How often is a Wernicke’s diagnosis missed and what are the consequences?

  Wernicke’s encephalopathy is correctly diagnosed in 1 of 22 patients. The classic features of confusion due to encephalopathy, variable ophthalmoplegia, and ataxia may be complete, or only one or two of the features may be present. Untreated, patients can become comatose and death can result.

• 15.

  Which dementia syndromes are associated with alcohol?

  The DSM-IV includes alcohol amnestic syndrome (Korsakoff’s syndrome), in which the amnestic disorder predominates, as well as a more generalized dementia associated with alcoholism. Both are associated with some degree of visuospatial impairment; neither includes aphasia. Patients with or without dementia may experience an acute, alcohol-related delirium known as Wernicke’s encephalopathy (usually with confusion, eye movement abnormalities, and ataxia).