Major or mild vascular NCD can occur at any age, although the prevalence increases ex- ponentially after age 65 years. In older individuals, additional pathologies may partly ac- count for the neurocognitive deficits. The course may vary from acute onset with partial improvement to stepwise decline to progressive decline, with ﬂuctuations and plateaus of varying durations. Pure subcortical major or mild vascular NCD can have a slowly pro- gressive course that simulates major or mild NCD due to Alzheimer’s disease.
Environmental. The neurocognitive outcomes of vascular brain injury are inﬂuenced by neuroplasticity factors such as education, physical exercise, and mental activity.
Genetic and physiological. The major risk factors for major or mild vascular NCD are the same as those for cerebrovascular disease, including hypertension, diabetes, smoking, obesity, high cholesterol levels, high homocysteine levels, other risk factors for atherosclerosis and ar- teriolosclerosis, atrial fibrillation, and other conditions increasing the risk of cerebral emboli.
Cerebral amyloid angiopathy is an important risk factor in which amyloid deposits occur within arterial vessels. Another key risk factor is the hereditary condition cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or CADASIL.
Structural neuroimaging, using MRI or CT, has an important role in the diagnostic pro- cess. There are no other established biomarkers of major or mild vascular NCD.
Major or mild vascular NCD is commonly associated with physical deficits that cause ad- ditional disability.
Other neurocognitive disorders. Since incidental brain infarctions and white matter le- sions are common in older individuals, it is important to consider other possible etiologies when an NCD is present. A history of memory deficit early in the course, and progressive worsening of memory, language, executive function, and perceptual-motor abilities in the absence of corresponding focal lesions on brain imaging, are suggestive of Alzheimer’s disease as the primary diagnosis. Potential biomarkers currently being validated for Alz- heimer’s disease, such as cerebrospinal ﬂuid levels of beta-amyloid and phosphorylated tau, and amyloid imaging, may prove to be helpful in the differential diagnosis. NCD with
Lewy bodies is distinguished from major or mild vascular NCD by its core features of ﬂuc- tuating cognition, visual hallucinations, and spontaneous parkinsonism. While deficits in executive function and language occur in major or mild vascular NCD, the insidious onset and gradual progression of behavioral features or language impairment are characteristic of frontotemporal NCD and are not typical of vascular etiology.
Other medical conditions. A diagnosis of major or mild vascular NCD is not made if other diseases (e.g., brain tumor, multiple sclerosis, encephalitis, toxic or metabolic disor- ders) are present and are of sufficient severity to account for the cognitive impairment.
Other mental disorders. A diagnosis of major or mild vascular NCD is inappropriate if the symptoms can be entirely attributed to delirium, although delirium may sometimes be superimposed on a preexisting major or mild vascular NCD, in which case both diagnoses can be made. If the criteria for major depressive disorder are met and the cognitive impair- ment is temporally related to the likely onset of the depression, major or mild vascular
NCD should not be diagnosed. However, if the NCD preceded the development of the de- pression, or the severity of the cognitive impairment is out of proportion to the severity of the depression, both should be diagnosed.