Beyond the neurocognitive disorder (NCD) syndrome (Criterion A), the core features of ma- jor or mild NCD due to Alzheimer’s disease include an insidious onset and gradual pro- gression of cognitive and behavioral symptoms (Criterion B). The typical presentation is amnestic (i.e., with impairment in memory and learning). Unusual nonamnestic presen— tations, particularly visuospatial and logopenic aphasic variants, also exist. At the mild
NCD phase, Alzheimer’s disease manifests typically with impairment in memory and leam- ing, sometimes accompanied by deficits in executive function. At the major NCD phase, visuoconstructional/perceptual motor ability and language will also be impaired, partic- ularly when the NCD is moderate to severe. Social cognition tends to be preserved until late in the course of the disease.
A level of diagnostic certainty must be specified denoting Alzheimer’s disease as the ”probable” or ”possible” etiology (Criterion C). Probable Alzheimer’s disease is diagnosed in both major and mild NCD if there is evidence of a causative Alzheimer’s disease gene, ei- ther from genetic testing or from an autosomal dominant family history coupled with au- topsy confirmation or a genetic test in an affected family member. For major NCD, a typical clinical picture, without extended plateaus or evidence of mixed etiology, can also be diagnosed as due to probable Alzheimer’s disease. For mild NCD, given the lesser de- gree of certainty that the deficits will progress, these features are only sufficient for a possible Alzheimer’s etiology. If the etiology appears mixed, mild NCD due to multiple eti- ologies should be diagnosed. In any case, for both mild and major NCD due to Alzhei- mer’s disease, the clinical features must not suggest another primary etiology for the NCD (Criterion D).
In specialty clinical settings, approximately 80% of individuals with major NCD due to also frequent at the mild NCD stage of impairment. These symptoms are as or more dis- tressing than cognitive manifestations and are frequently the reason that health care is sought. At the mild NCD stage or the mildest level of major NCD, depression and / or ap- athy are often seen. With moderately severe major NCD, psychotic features, irritability, agitation, combativeness, and wandering are common. Late in the illness, gait distur- bance, dysphagia, incontinence, myoclonus, and seizures are observed.
The prevalence of overall dementia (major NCD) rises steeply with age. In high—income countries, it ranges from 5% to 10% in the seventh decade to at least 25% thereafter. US.
census data estimates suggest that approximately 7% of individuals diagnosed with Alz- heimer’s disease are between ages 65 and 74 years, 53% are between ages 75 and 84 years, and 40% are 85 years and older. The percentage of dementias attributable to Alzheimer’s disease ranges from about 60% to over 90%, depending on the setting and diagnostic cri- teria. Mild NCD due to Alzheimer’s disease is likely to represent a substantial fraction of mild cognitive impairment (MCI) as well.
Major or mild NCD due to Alzheimer’s disease progresses gradually, sometimes with brief plateaus, through severe dementia to death. The mean duration of survival after di-
Major or Mild Neurocognitive Disorder Due to Alzheimer’s Disease 613 agnosis is approximately 10 years, reﬂecting the advanced age of the majority of individ- uals rather than the course of the disease; some individuals can live with the disease for as long as 20 years. Iate-stage individuals are eventually mute and bedbound. Death most commonly results from aspiration in those who survive through the full course. In mild