Skip to Main Content


Dementia, a syndrome with many causes, affects >4 million Americans and results in a total health care cost of >$100 billion annually. It is defined as an acquired deterioration in cognitive abilities that impairs the successful performance of activities of daily living. Memory is the most common cognitive ability lost with dementia; 10% of persons >70 and 20–40% of individuals >85 have clinically identifiable memory loss. In addition to memory, other mental faculties may be affected; these include language, visuospatial ability, calculation, judgment, and problem solving. Neuropsychiatric and social deficits also arise in many dementia syndromes, resulting in depression, apathy, hallucinations, delusions, agitation, insomnia, and disinhibition. The most common forms of dementia are progressive, but some are static and unchanging or fluctuate from day to day or even minute to minute. Most patients with Alzheimer's disease (AD), the most prevalent form of dementia, begin with memory impairment, although in other dementias, such as frontotemporal dementia, memory loss is not a presenting feature. Focal cerebral disorders are discussed in Chap. 26 and illustrated in a video library in Chap. e10; memory loss is discussed in Chap. e9.


Dementia syndromes result from the disruption of specific large-scale neuronal networks; the location and severity of synaptic and neuronal loss combine to produce the clinical features (Chap. 26). Behavior and mood are modulated by noradrenergic, serotonergic, and dopaminergic pathways, whereas cholinergic signaling is critical for attention and memory functions. The dementias differ in the relative neurotransmitter deficit profiles; accordingly, accurate diagnosis guides effective pharmacotherapy.


AD begins in the transentorhinal region, spreads to the hippocampus, and then moves to lateral and posterior temporal and parietal neocortex, eventually causing a more widespread degeneration. Vascular dementia is associated with focal damage in a random patchwork of cortical and subcortical regions or white matter tracts that disconnect nodes within distributed networks. In keeping with the anatomy, AD typically presents with memory loss accompanied later by aphasia or navigational problems. In contrast, patients with dementias that begin in frontal or subcortical regions such as frontotemporal dementia (FTD) or Huntington's disease (HD) are less likely to begin with memory problems and more likely to have difficulties with judgment, mood, and behavior.


Lesions of cortical-striatal pathways produce specific effects on behavior. The dorsolateral prefrontal cortex bears connections with a central band of the caudate. Lesions of either node or connecting white matter pathways result in poor organization and planning, decreased cognitive flexibility, and impaired working memory. The lateral orbital frontal cortex connects with the ventromedial caudate. Lesions of this system cause impulsiveness, distractibility, and disinhibition. The anterior cingulate cortex projects to the nucleus accumbens, and interruption of these connections produces apathy, poverty of speech, or even akinetic mutism. All corticostriatal systems also include topographically organized projections through the pallidum and thalamus, and damage to these nodes can likewise reproduce the clinical syndrome of corticostriatal damage.


The Causes of Dementia


Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessMedicine Full Site: One-Year Subscription

Connect to the full suite of AccessMedicine content and resources including more than 250 examination and procedural videos, patient safety modules, an extensive drug database, Q&A, Case Files, and more.

$995 USD
Buy Now

Pay Per View: Timed Access to all of AccessMedicine

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.