Special Report: Neuropsychiatry
Alzheimer disease (AD) is an acquired neurodegenerative disease that causes persistent and progressively worse dementia. The cognitive deficits of AD include disturbances of language (aphasia); calculation (dyscalculia); visuospatial integrity; motor programming (apraxia); recognition (agnosia); and planning, organization, and problem solving (executive dysfunction). The clinical presentation of AD progresses through 3 stages of severity: mild, moderate, and severe (Table 1).
Neuropsychiatric symptoms associated with dementia, and particularly with AD, have been noted in more than 80% of patients.1 Lyketsos and colleagues2 reported findings from a population study of 5092 community residents (representing 90% of the elderly population of Cache County, Utah). A number of neuropsychiatric disturbances (apathy, irritability, anxiety, delusions, elation, and disinhibition) were reported with similar severity at all stages of dementia.
In contrast, agitation, aggression, and aberrant motor behavior were more common in the later stages of AD. Depression and hallucinations were slightly more prevalent in moderately severe dementia than in mildly severe dementia. Results of this and similar analyses suggest that frank psychotic symptoms are more common in advanced stages of dementia. Generally, patients with AD manifest diminished awareness of their disability (anosagnosia).
In mild AD, the earliest stage of illness, the affected patient appears remarkably forgetful; the patient has a tendency to forget conversations and recent events and will repetitively ask the same questions about planned appointments or activities. Patients are noted to misplace items more easily and to search for them, expressing great frustration in the process.
In its earliest clinical stages, AD also leads to a subtle impairment in expressive language. The patient increasingly pauses to find words, and spontaneous discourse has a vague, rambling quality. These are signs of anomia, a loss of the ability to readily access words (especially nouns and verbs) when conversing or writing.
At this initial stage of the clinical presentation, there will be evidence that the patient is not quite as well organized as in the past. The ability to plan and organize work, personal finances, and other instrumental activities becomes increasingly impaired and requires supervision and assistance. For example, it may appear to others that the patient has an unusual degree of difficulty in learning how to use a new appliance in the home. Often, afflicted patients will begin to show some difficulty in navigational ability. There is an increasing risk of getting lost while driving or finding one’s way in a crowded area, such as a shopping mall.
In mild AD, the neuropsychiatric alterations noted in affected patients are generally subtle and variable in impact. Most commonly, patients seem apathetic: they have less drive and motivation to engage in recreational and other activities. Families will often note that the patient seems content to sit quietly for uncharacteristically long periods. In some patients, emotional display becomes coarser, more intense, and more labile. Some patients are prone to depressive symptoms, anxiety, and irritability. Generally, these symptoms are intermittent and mild.
1. Cummings JL. Alzheimer’s disease. N Engl JMed.
2. Lyketsos CG, Steinberg M, Tschanz JT, et al. Mental
and behavioral disturbances in dementia: findings
from the Cache County Study on Memory in Aging.
Am J Psychiatry. 2000;157:708-714.
3. Doody RS, Stevens JC, Beck C, et al. Practice
parameter: management of dementia (an evidencebased
review). Report of the Quality Standards
Subcommittee of the American Academy of
Neurology. Neurology. 2001;56:1154-1166.
4. Ritchie CW, Ames D, Clayton T, Lai R. Metaanalysis
of randomized trials of the efficacy and safety of
donepezil, galantamine, and rivastigmine for the
treatment of Alzheimer disease. Am J Geriatr
5. Winblad B, Engedal K, Soininen H, et al. A 1-year,
randomized, placebo-controlled study of donepezil
in patients with mild to moderate AD. Neurology.
6. Raskind MA, Peskind ER, Wessel T, Yuan W.
Galantamine in AD: a 6-month randomized, placebocontrolled
trial with a 6-month extension. The
Galantamine USA-1 Study Group. Neurology.
7. Rogers SL, Doody RS, Pratt RD, Ieni JR. Longterm
efficacy and safety of donepezil in the treatment
of Alzheimer’s disease: final analysis of a US
multicentre open-label study. Eur Neuropsychopharmacol.
8. Reisberg B, Doody R, Stoffler A, et al. Memantine
in moderate-to-severe Alzheimer’s disease. N Engl
J Med. 2003;348:1333-1341.
9. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine
treatment in patients with moderate to severe Alzheimer
disease already receiving donepezil: a randomized
controlled trial. JAMA. 2004;291:317-324.
10. Winblad B, Poritis N. Memantine in severe
dementia: results of the 9M-BEST Study (Benefit and
efficacy in severely demented patients during treatment
with memantine). Int J Geriatr Psychiatry.
11. Kmietowicz Z. NICE proposes to withdraw
Alzheimer’s drugs from NHS. BMJ. 2005;330:495