Dementia is one of the most common neurological disorders affecting millions of people living in the United States. The neurohospitalist is often consulted by medical teams to ascertain the cause of the decline in a person’s cognition. Behavioral decompensation often due to delirium complicating dementia is another common trigger for neurological consultation. Therefore, it is important to recognize the signs and symptoms of dementia in hospitalized patients, as early recognition can allow measures to prevent acute confusional states, treat underlying diseases that can induce dementia, provide symptomatic relief, and facilitate discharge planning.

For practical purposes, dementia has four characteristics:¹

1. Decline in more than one cognitive domain: Cognitive domains are a group of related cognitive functions that are often mediated by the same or similar networks in the brain (we will elaborate on this below). A decline in cognitive functioning often manifests itself as concerns expressed by the patients themselves or an informed care-giver who may have better insight into the patient’s functioning. The importance of collateral history cannot be overemphasized, as anosognosia (unawareness of dysfunction) is commonly associated with dementing disorders. If the patient is on their own in the hospital, it is often worthwhile to call family or the nursing home to get a more reliable and detailed account of daily functioning. Once dementia is suspected, some form of neuropsychological testing should confirm historical insights. In the hospital setting, given the lack of access to inpatient neuropsychology and coexistence of delirium with dementia, it is often not possible to do extensive formal testing. In this case, a short form such as Montreal Cognitive Assessment (www.mocatest.org) supplemented with tailored higher function testing may be useful.

2. Delirium by itself cannot explain all the symptoms: Whereas dementia is a chronic decline in cognition, delirium is an acute confusional state often due to systemic medical conditions, which are potentially reversible. Common causes may include electrolyte abnormalities, systemic infections, hypoxia, pain, intoxication and medication side effect or withdrawal, organ failure, and disruption of sleep cycle. In the hospital setting, delirium and dementia often coexist, as the presence of dementia is a major risk factor for the development of delirium. We will explore the characteristics of delirium later in this chapter.

3. “Reversible causes of dementia” are excluded:² These are causes of cognitive decline that, if treated, can either reverse the decline or stop its progression. Our hope is that one day neurodegenerative dementias would fall into this category but presently only a small minority of patients belong to this group. One way to remember the common reversible causes of dementia is by the mnemonic Vitamin CDE:

   • Vascular: Imaging should be performed in patients with suspected dementias. Subdural hematomas, more common in the elderly population, can cause cognitive decline without any focal neurological signs. Stroke, both hemorrhagic and ischemic, may be associated with cognitive decline but they are often less subtle. Patients can have small strokes or lacunes as well as ischemic demyelination.

   • Infectious: Infections of the central nervous system (CNS) can cause a chronic decline in mental faculties, including syphilis, HIV, and fungal infections. Diseases such as herpes encephalitis and even bacterial meningitis and encephalitis can cause an acute decline. For a more detailed discussion of CNS infections, please refer to the chapter on rapidly progressive dementias. Systemic infections such as pneumonia and urinary tract infections can also precipitate delirium and should be ruled out.

   • Tumor: CNS neoplasms and other space-occupying lesions could affect higher cortical functions. We have covered some of these in the chapter on rapidly progressive dementias.

   • Alcohol (and other intoxicants): Alcohol intoxication and withdrawal can precipitate confusion. Chronic alcohol abuse can lead to Wernicke encephalopathy and Korsakoff syndromes due to thiamine deficiency and Marchiafava-Bignami disease. A more common presentation is a chronic syndrome that may resemble one of the neurodegenerative dementias.

   • Metabolic and deficiency diseases: For this category, think of B12, vitamin D, folate deficiencies, and electrolyte abnormalities. These are covered in Chapter 32.

   • Iatrogenic: Medications, especially those with anticholinergic activity, can worsen cognition. Traditional anticholinergics such as benztropine, used for tardive dyskinesia, are obvious candidates, but many other drugs used for other purposes such as tricyclic antidepressants and antihistamines also have anticholinergic effects. Other medications that may causes of delirium include benzodiazepines, opiates, and high doses of steroids. Intoxication with lithium, heavy metals, manganese, and bismuth can also present with confusion.

   • Nonorganic: Conversion and factitious disorders are not uncommon causes of cognitive problems.

   • Chronic systemic disease: Classically hepatic encephalopathy can present as a dementia syndrome. But other chronic diseases such as renal failure, heart failure, chronic obstructive pulmonary disease, autoimmune disorders, and anemias, among other medical diseases, can precipitate a decline in mental status.

   • Depression: Depression is one of the most common causes of cognitive decline in the elderly. The presentation of depression in the elderly may differ from that of younger patients, in that it may predominantly manifest as anhedonia, psychomotor retardation, and cognitive problems. Commonly patients complain about problems with episodic memory and concentration.

   • Endocrine: Endocrinopathies can induce dementia: both hypothyroidism and hyperthyroidism can cause cognitive problems. Cushing’s disease can cause a picture similar to steroid psychosis. Hypoglycemia is a cause of recurrent confusion in patients who use insulin; however, hyperosmolar hyperglycemia can also present with confusion (Table 33-1).

4. It interferes with activities of daily living:³ Activities of daily living are a means by which we can assess the functional implications of cognitive decline. They are typically divided into two groups:

   • Basic Activities of Daily Living: These are the tasks that an individual has to carry out for self-care. These include the ability to mobilize, dress, eat independently, and attend to personal hygiene.

   • Instrumental Activities of Daily Living: These are tasks that allow an individual to live independently in the community. The tasks include housework, food preparation, taking medication, shopping, use of telephone, and ability to use transportation.

Cognitive domains are groups of related higher cortical functions, which are the subject of study in clinical neuropsychology, behavioral neurology, and neuropsychiatry. Their usefulness arises from the fact that similar functions are mediated by similar brain networks and are often affected together when brain injury or degeneration occurs. For those who want to learn more about disorders in the various cognitive domains, we recommend texts such as “Clinical Neuropsychology” by Heilman and Valenstein. However, the following is a brief description of some of the domains that may be degraded in patients with dementia.

1. Memory: Memory is the ability to encode, store, and retrieve information. Memory may be nondeclarative as is the case with procedural memory (learning or using a previously learned skill such as riding a bicycle), perceptual memory, and implicit memory such as the phenomenon of priming. Here we will concentrate on declarative memory that includes episodic memory (ie, when, where, and who) and semantic memory (ie, knowledge). Declarative memory often requires the act of “remembering,” whereas as nondeclarative memory is unconscious and can be deduced from its effect on behavior. Working memory is better discussed in the context of executive functions (Figure 33-1).

   Episodic memories relate to events that are categorized by when (time) and where (location) they occurred, as well as who was involved. For example, recalling what one had for breakfast includes a time and place where the meal was consumed, as well as who was present. Recalling a vague memory from childhood is also an episodic memory even if one cannot remember when or where it occurred. This is because in spite of our inability to recall the details, it did occur at a particular time and at a specific location. One of the laws of dementia is Ribot’s rule, which describes the often observed phenomenon where more recent episodic memories are more vulnerable to being forgotten than remote memories. The patient may complain that they have problems remembering recent conversations or where they placed something but can recall details of their wedding day or some other significant event in their lives. An isolated problem with episodic memory is called amnesia and is seen in the case of damage to mesial temporal cortex where the hippocampus is located, as seen, for example, in untreated herpes encephalitis or hypoxia. Less commonly it is due to damage to other parts of the memory circuit known as the Papez circuit, which includes the hippocampus, the fornix, the mammillary bodies, the mammillothalamic tract, the anterior thalamus, and the cingulate gyrus along with the retrosplenial cortex. Examples include patients with Korsakoff’s psychosis (eg, amnesia and confabulation associated with alcoholism and thiamine deficiency, Figure 33-2). Injury to the basal forebrain, which supplies acetylcholine to the hippocampus, can also cause disorders of episodic memory. Injury to the left Papez circuit usually causes a verbal memory deficit and, with injury to the right side, a visuospatial memory deficit (this is of course an over-simplification). Transient lapses in memory function can also occur in transient global amnesia (a self-limited benign condition of uncertain etiology) and in partial complex seizures.

   The other kind of declarative memory is semantic memory, which is knowledge of facts. One may know, for example, that giraffe is the tallest land animal on planet earth. Certain neurological conditions such as variants of frontotemporal dementia affecting the lateral temporal lobes can cause semantic dementia. Loss of semantic memory can present with a loss of the comprehension of words and concepts. These patients also commonly have problems with naming and have problems with relating pictures of semantically related objects. The latter is the case because the problem is not one of language, but the entire knowledge of particular objects is degraded in semantic dementia. Patients with Alzheimer disease may also have a loss of semantic memories.

2. Visuospatial: The brain processes visuospatial information along two pathways: the dorsal and ventral visual pathways (Figure 33-3B). The dorsal pathway, also known as the “where” pathway, determines the relationship of objects to the viewer. In extreme cases where there is bilateral damage to the parieto-occipital cortices, patients may reveal signs of the Balint’s syndrome with optic ataxia, where a person misreaches for objects. An inability to discern the relationships of objects to one another may cause a deficit in processing of the “whole picture.” For example, if the picture on the card illustrated in Figure 33-3C is presented to such a patient, at one sitting she may describe the children raiding the cookie jar and be unaware of the woman at the sink. In another sitting, she may see the woman and not the children. This is called simultanagnosia or inability to see the whole picture simultaneously. This is formally assessed by presenting the patient with Navon figures, larger shapes or letters made up of smaller ones (Figure 33-3A). A patient with simultanagnosia may look at a triangle made up of smaller squares and only see squares. Defects in the dorsal stream can also induce an inability to saccade to specific locations in space also known as ocular apraxia. The combination of simultanagnosia, optic ataxia, and ocular apraxia are the constituents of Balint’s syndrome. In certain presentations of Alzheimer’s disease, the patient may have varying degrees of dysfunction of the dorsal stream. At the most basic level, an inability to navigate may arise from an ignorance of the relationship of locations with respect to one another. In more severe cases, a complete Balint’s syndrome may be seen. Other disorders of visual processing include akinotopsia and hemispatial neglect or inattention. The latter occurs when the right parietal lobe is involved and patients with this disorder fail to attend to the left side of the space (Figure 33-3).

   The ventral pathway, or the “what pathway,” decodes the features of particular objects. Defects in the ventral pathway can cause visual agnosia (inability to discern objects), prosopagnosia (loss of face recognition), and cerebral achromatopsia (inability to distinguish colors). This is sometime seen in variants of Alzheimer disease called posterior cortical degeneration, as a presenting symptom. Patients may complain that they cannot recognize faces, even though the ophthalmologist will not find anything wrong with the eyes, such as changes in visual acuity.

3. Language: Please see chapter 23.

4. Social Cognition: Social cognition is the cognitive function that allows us to make assessments of social situations, of the people present in that situation, and anticipate their likely responses and attitudes toward ourselves and each other. People with damage to their orbitofrontal cortices may often have problems with appropriate behavior in certain contexts. We are aware of the extremes of these behaviors such as when someone has sexually inappropriate behavior or discharges their bodily functions in public. However, in most situations the change is more subtle and may involve problems with inappropriate jokes and comments, or behaving in ways that are out of context (for example, dancing to the national anthem). Social cognition is classically associated with behavioral variants of frontotemporal dementia.

5. Executive Functions: The executive functional networks allow us to step back from the immediacy of experience (to paraphrase psychiatrist Iain McGilchrist)⁵ so that we are able to plan, initiate, sequence, and monitor our cognitive and motor activities. We also need to inhibit irrelevant behaviors and persist at a task until it is completed, but not to continue after it is completed (perseveration) or if it appear this approach is unsuccessful. Executive dysfunction, seen with frontal lobe injuries and dementias, can manifest in a variety of ways. The care-giver might complain of the patient’s difficulty in planning, disorganization, and lack of insight. Some of the easier bedside tests of executive functions are as follows:

   • Working memory: Working memory is the ability to immediately retain information such as a series of numbers or packets of information for long enough to be able to manipulate this information or use this information to guide actions. For example, when one is asked to repeat a phone number, one does this by using working memory. If asked 2 hours later to recall these numbers, unless an effort was made to store-encode these numbers in memory, we most likely would not remember them. The evanescence of working memory is one of its defining characteristics. To test working memory, the patient is asked to repeat a string of numbers both forward and backwards. The longest string of numbers repeated by the patient is a measure of her working memory and its integrity.

   • Motor sequencing: The patient is asked to imitate the examiner performing a sequence of 3 sequential actions in a row such as tapping their lap with their fist, edge of their hand then their palm.

   • Pre-potent response inhibition: Certain reactions are preferred by the brain. For example, our natural tendency is to blink if hit with a finger between the eyes or to imitate an observed action (“monkey see monkey do”). A person with intact executive functioning is able to suppress this tendency in response to instructions. For example, the examiner may ask the patient not to blink their eyes while she taps on the glabella. An inability to do this is called Myerson’s sign. Another easy test is to ask the patient to hold up one figure when the examiner holds up 2 and vice versa. A tendency to imitate the examiner may be seen in patients with executive dysfunction.

   • On the MoCA, there are several items that can be useful in testing executive function provided that visuospatial functioning is intact. The Trails B test, which requires the patient to alternate numbers and letters, requires set shifting, which can be impaired in patients with executive dysfunction. The drawing of clocks and setting the hands to “ten after eleven” can also reveal poor strategy in the task of construction. Patients with frontal lobe dysfunction also have trouble activating and search language-speech network and thus may have a reduction in verbal fluency. The MoCA tests this by having patients in one minute name as many words as possible with the letter F, but not to use numbers or proper names. Other neuropsychological tests that are used to examine executive functions are the Wisconsin sorting test and the Stroop test.

6. Praxis: Praxis is the ability to execute purposeful skilled movements. Apraxia is a disorder of the programming of purposeful goal-oriented movements. Whenever someone is unable to carry out skilled tasks in the absence of any sensory or motor impediments, one possibility is apraxia. Patients with Alzheimer disease often exhibit elements of apraxia. An asymmetrical apraxia is often seen in patients with corticobasal degeneration. Several kinds of apraxia are caused by damage to dominant hemisphere’s frontal lobe, and parietal lobes as well as the anterior corpus callosum:

   • Conceptional apraxia: This is a loss of basic knowledge of tool use. The patient may not recognize what needs to be done in a particular situation or what tools to use.

   • Ideational apraxia: This disorder refers to an inability to sequence actions needed to accomplish a larger task. The patient, for example, is asked how they would make a peanut butter and jelly sandwich. The ability of the patient to know and sequence the steps needed for this overall task is then assessed.

   • Ideomotor apraxia: Patients with this disorder have a problem correctly performing the required movements and postures needed for tool use. For testing, the patient is asked to perform particular pantomime actions: “How would you use a screwdriver with your left hand?” After advised not to use a part of their body as the tool, the patient may mistakenly use their index finger as a surrogate for the tool or move the incorrect joints. For orobuccal apraxia, the patient is asked to blow a kiss or to blow out a match.

   • Limb-kinetic apraxia: In this disorder, there is a loss of hand-finger deftness. This loss is most often caused by damage to the motor or premotor cortex in patients with strokes or dementias. One of the most sensitive tests is to have the patient rotate a coin between the thumb, index finger, and middle fingers. The inability to deftly carry out this task indicates the patient has limb-kinetic apraxia.