Like age, culture, and occupation, gender issues may affect the level of concern and aware- ness of cognitive symptoms. In addition, for late-life NCDs, females are likely to be older, to have more medical comorbidity, and to live alone, which can complicate evaluation and treatment. In addition, there are gender differences in the frequency of some of the etio- logical subtypes.
In addition to a careful history, neuropsychological assessments are the key measures for diagnosis of NCDs, particularly at the mild level, where functional changes are minimal and symptoms more subtle. Ideally, individuals will be referred for formal neuropsycho— logical testing, which will provide a quantitative assessment of all relevant domains and thus help with diagnosis; provide guidance to the family on areas where the individual may require more support; and serve as a benchmark for further decline or response to therapies. When such testing is unavailable or not feasible, the brief assessments in Table 1 can provide insight into each domain. More global brief mental status tests may be helpful but may be insensitive, particularly to modest changes in a single domain or in those with high premorbid abilities, and may be overly sensitive in those with low premorbid abilities.
In distinguishing among etiological subtypes, additional diagnostic markers may come into play, particularly neuroimaging studies such as magnetic resonance imaging scans and positron emission tomography scans. In addition, specific markers may be in- volved in the assessment of specific subtypes and may become more important as addi- tional research findings accumulate over time, as discussed in the relevant sections.
By definition, major and mild NCDs affect functioning, given the central role of cognition in human life. Thus, the criteria for the disorders, and the threshold for differentiating mild from major NCD, are based in part on functional assessment. Within major NCD there is a broad range of functional impairment, as implemented in the severity specifiers. In addition, the specific functions that are compromised can help identify the cognitive domains affected, particularly when neuropsychological testing is not available or is difficult to interpret.
Normal cognition. The differential diagnosis between normal cognition and mild NCD, as between mild and major NCD, is challenging because the boundaries are inherently ar- bitrary. Careful history taking and objective assessment are critical to these distinctions. A longitudinal evaluation using quantified assessments may be key in detecting mild NCD.
Delirium. Both mild and major NCD may be difficult to distinguish from a persistent de- lirium, which can co-occur. Careful assessment of attention and arousal will help to make the distinction.
Major depressive disorder. The distinction between mild NCD and major depressive disorder, which may co-occur with NCD, can also be challenging. Specific patterns of cog- nitive deficits may be helpful. For example, consistent memory and executive function deficits are typical of Alzheimer’s disease, whereas nonspecific or more variable perfor- mance is seen in major depression. Alternatively, treatment of the depressive disorder with repeated observation over time may be required to make the diagnosis.
Specific learning disorder and other neurodevelopmental disorders. A careful clari- fication of the individual’s baseline status will help distinguish an NCD from a specific learning disorder or other neurodevelopmental disorders. Additional issues may enter the differential for specific etiological subtypes, as described in the relevant sections.
NCDs are common in older individuals and thus often co-occur with a wide variety of age- related diseases that may complicate diagnosis or treatment. Most notable of these is delirium, for which NCD increases the risk. In older individuals, a delirium during hos- pitalization is, in many cases, the first time that an NCD is noticed, although a careful his- tory will often reveal evidence of earlier decline. Mixed NCDs are also common in older individuals, as many etiological entities increase in prevalence with age. In younger indi- viduals, NCD often co-occurs with neurodevelopmental disorders; for example, a head in-
Major or Mild Neurocognitive Disorder Due to Alzheimer's Disease 611 jury in a preschool child may also lead to significant developmental and learning issues.