Dementia: General Considerations

Chapter: Dementia: General Considerations
McMaster Section Editor(s): Robert B. Zipursky, Rebecca Anglin
McMaster Author(s): Eric Wong, Richard Sztramko, Christopher Patterson
Additional Information

Definition, Etiology, PathogenesisTop

Dementia is a common syndrome of acquired cognitive deficits which interfere with daily function and are not due to other conditions such as delirium or severe depression. Most commonly dementia is due to neurodegenerative conditions such as Alzheimer disease (AD) or less frequently due to cerebrovascular disease, trauma, infections, and numerous other causes. In order to destigmatize the label of dementia, the latest edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term major neurocognitive disorder to replace dementia; however, the definition is essentially the same.

The formal definition of dementia is cognitive or behavioral symptoms that represent a decline from previous levels of function; interfere with daily function; are not explained by delirium or psychiatric illness; could be detected by history and cognitive testing; and include ≥2 of amnesia, agnosia, aphasia, executive dysfunction, and behavior change (eg, apathy, disinhibition). The gradual onset, progressive changes, irreversibility, and memory loss as essential features are absent from the current definition, as these features, which are typical of AD, are not necessarily present in other types of dementia.

Pathologic subtypes: In Canada and most of developed countries, AD is the most prevalent pathologic process causing dementia. Nearly 50% of cases of dementia are attributable to AD, and a further one-third is due to multiple pathologies, most commonly AD with cerebrovascular disease. The other principal neurodegenerative diseases are frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB). Nowadays pure vascular dementia is considered to be relatively uncommon. FTD is distinct pathologically and usually also clinically from AD. Genetic influences account for ~50% of FTD cases. DLB is related to Parkinson disease (PD), and a family history of PD may be present. Primary PD is also associated with high risk of developing dementia.

Mild cognitive impairment (MCI) refers to the period of asymptomatic disease that precedes the onset of symptoms of dementia and is associated with preserved daily function. For example, in the case of AD the onset of dementia is usually preceded by a period of mild memory deficits, which do not compromise daily function. This is known as amnestic MCI and in the DSM-5 definition termed minor neurocognitive disorder.

Risk factors: While many of risk factors parallel those for cardiovascular and cerebrovascular disease (eg, diabetes mellitus, hypertension, smoking, prior stroke, physical inactivity), risk factors unique to dementia include repeated or severe head trauma, exposure to pesticides, fewer years of education, and use of anticholinergic drugs. The greatest risk factor by far is age, and the increasing prevalence of dementia is largely attributable to increasing life expectancy.

Genetic factors: Genetic influences are important in early-onset Alzheimer disease (EOAD), in which autosomal dominant transmission may occur. EOAD accounts for <2% of all cases of dementia. Single gene mutations in amyloid precursor protein (APP) and presenilin (PS1, PS2) genes confer 100% probability of developing EOAD, as does Down syndrome (trisomy 21). Spontaneous mutations may occur but many cases of EOAD do not have these gene abnormalities. In the far more common late-onset Alzheimer disease (LOAD) genetic factors play a less obvious role and no deterministic gene abnormalities have so far been identified. For example, in the APO E gene system on chromosome 19 there are three alleles: ε2, ε3, and ε4. While the presence of ε2 lowers the risk for AD and ε3 is neutral, possessing 1 or (worse) 2 copies of ε4 increases the risk of LOAD.

Clinical Features and Natural HistoryTop

1. AD: AD is a neurodegenerative condition characterized by neuronal death and accumulation of the toxic protein aggregates beta-amyloid and tau.

The most common first symptom is impairment in memory. At first this usually affects recent or episodic memory and may go unnoticed by the individual. The cognitive decline is usually noticed first by spouses, other family members, and coworkers. Family members will often complain of the patient repeating questions, repeating stories, losing objects, and not being able to remember discrete conversations or events. Because the onset is insidious and progression is gradual, the date of onset is typically difficult to ascertain. Over time, other cognitive functions are affected: often language (especially word retrieval), executive function (the ability to plan and sequence complex tasks), visuospatial function (the ability to orient oneself in one’s environment), and praxis (the ability to perform learned motor skills). As these deficits increase, difficulty is experienced in performing familiar tasks (eg, the electrician can no longer change a light bulb, the gourmet cook can no longer prepare a meal). Not being able to find appropriate words, becoming lost in familiar environments, and not being able to use household objects (eg, remote control) are also common complaints. As the disease progresses further, behavior problems such as apathy, irritability, and aggression may supervene.

In the final stages of the disease motor function may be affected. Swallowing difficulty, rigidity, and contractures may announce end-stage AD. The average duration from first symptoms to death is generally within 7 to 10 years, but in the Canadian Study of Health and Aging the average life expectancy was only 3.4 years. However, in this longitudinal study the average age of onset was 81 years (~10 years later than the usual onset). At age 81, the usual life expectancy is ~5 years.

Notwithstanding the more typical amnestic presentation of AD, several different clinical phenotypes exist (Table 12.4-1), including a primarily language variant (logopenic primary progressive aphasia), frontal or executive variant, or visuospatial variant (posterior cortical atrophy).

2. FTD: In contrast to AD, the prominent early symptoms do not involve memory, but feature behavioral and/or language changes. This group of diseases may be as common as AD between the ages of 45 and 64 years, with an annual incidence of 15/100,000 in some studies. There are 3 principal variants of FTD: behavioral variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The latter two are language variants, presenting with progressive aphasia instead of behavioral changes. While initially one typically sees changes of behavior or language, as the disease progresses combinations of both types of symptoms develop, as originally described by Arnold Pick, whose name the condition previously bore (Table 12.4-2).

bvFTD is characterized by early onset of behavioral disinhibition (socially inappropriate behavior, impulsive actions); apathy or inertia (lack of goal-directed behaviors); loss of sympathy or empathy; obsessive/perseverative behaviors; hyperorality (binge eating, oral exploration of inedible objects), and a neuropsychologic profile displaying impaired executive function with intact episodic memory. When apathy is the most prominent feature, it may be difficult to distinguish from depression. Patients stop engaging in daily activities and may sit idle for hours a day watching television but usually they do not endorse depression symptoms. If disinhibition is present (eg, insulting strangers, inappropriate sexual behavior, stealing), the disease usually reaches the medical or legal system earlier than in cases where apathy predominates. Often the most concerning to caregivers is the lack of empathy, interrelatedness, and personal warmth. Traumatic or tragic events in the caregiver’s life may not register with the patient, making it extremely challenging for the caregiver to handle. Loss of insight is typical, which makes explaining and managing the disease particularly difficult.

In aphasic variants in FTD (SD and PNFA) language deficits are the most prominent and principal cause of impaired daily activities at disease onset. Patients with aphasic variants may evolve to resemble bvFTD in the course of their disease and occasionally develop movement disorders, including progressive supranuclear palsy and corticobasal syndrome. PNFA is characterized by effortful halting speech, with spared single-word comprehension and object knowledge. These patients may develop mutism over time. By contrast, SD has spared speech production (motor and grammar) but has difficulties with confrontational naming, single-word comprehension, and objective knowledge. Patients with SD may describe a zebra as an animal, then later as a thing. They may suffer from semantic paraphasias and call objects by their incorrect names. The meaning of words and symbols may be lost.

FTD shares the underlying pathology with movement disorders, and the evolution of a clinical phenotype means that a patient may start out with one disorder and progress to look like a different disorder over time. For example, a patient with behavioral disinhibition and apathy, resembling a case of bvFTD, may evolve over time to develop rigidity and tremor, apraxia, and dystonia, and be better classified as with frontal features. Similarly, a person with PNFA may present with language difficulties, and then develop traits consistent with progressive supranuclear palsy. There is considerable clinical and pathophysiologic overlap among bvFTD, SD, PNFA, corticobasal syndrome, and progressive supranuclear palsy.

3. DLB: Lewy bodies, the aggregations of alpha synuclein that characteristically occur within the basal ganglia of individuals with PD, may also deposit within the cerebral cortex and other parts of the brain. Individuals with DLB exhibit hallucinations or delusions, fluctuations in the severity of symptoms, and spontaneous or drug-induced parkinsonism. The presentation with hallucinations and fluctuating attention renders the distinction from delirium particularly important. In many individuals finally diagnosed with DLB, a history of repeated, extensive investigations for the causes of delirium has occurred. Cognitively, disturbances in visuospatial performance are prominent in DLB: difficulties with clock drawing or completing the interlocking pentagons on the Mini Mental State Examination (MMSE) are clues to this diagnosis. DLB may be preceded by many years with rapid-eye movement sleep disorder, that is, acting out dreams, sometimes violently. Adverse reactions to neuroleptic agents including rigidity, bradykinesia and other extrapyramidal adverse effects are further clues to this diagnosis (Table 12.4-3).

4. Vascular dementia (vascular cognitive impairment [VCI]; Table 12.4-4): The concept of a vascular dementia has evolved considerably since the original descriptions of “multi-infarct dementia.” Observations from the Nun Study of Aging and Alzheimer’s Disease altered our understanding in that most dementias previously considered to be of vascular origin are actually due to the presence of cerebral vascular disease superimposed upon neurodegenerative conditions, such as AD. Individuals even with prominent pathologic changes of AD (neurofibrillary tangles and amyloid plaques) may appear cognitively normal in life, but the presence of even a single white matter stroke greatly increases the risk of that individual having a dementia.

5. Rapidly progressive dementia (RPD): This unusual condition is defined by a dementia which develops within 1 year from the individual being cognitively normal. There are many causes, including tumors; paraneoplastic syndromes, infections (eg, HIV); and metabolic, autoimmune, psychiatric, toxic, and vascular events. A significant portion of RPD is caused by neurodegenerative disease, such as AD. While the cause is not infrequently discovered by the usual diagnostic process (see below), causes such as Creutzfeldt-Jakob disease and anti-NMDA (N-methyl-D-aspartate-type) receptor encephalitis may be revealed by more elaborate investigations.

DiagnosisTop

The process of history examination and basic laboratory testing will usually allow the type of dementia to be identified. Insidious onset with progressive memory decline points towards AD. Onset of progressive aphasia usually indicates FTD or a language variant of AD. Prominent apathy may indicate FTD or frontal variant AD but mandates exclusion of depression as a potential diagnosis. Abrupt onset in the absence of a new medication or intercurrent infection points towards a vascular or mixed etiology. Simple neuroimaging studies may be added if indications are present.

1. History: By far the most important diagnostic tool is a careful history including collateral data from family and others. The timing and onset of symptoms, type of symptoms, any precipitating events, and risk factors are all important data elements. The prescription of a new medication, onset of systemic disease (eg, heart failure, pulmonary, renal or hepatic failure, hypothyroidism, infection), as well as psychiatric, family, educational, and occupational history are all important. It is usually necessary to consult other health-care professionals for background history. Findings such as “poor historian,” missing appointments, or poor adherence to prescribed medications are clues that should not be ignored.

2. Objective cognitive testing: Once the suspicion of a cognitive disorder is raised, physical examination and neurologic examination to detect focal signs together with brief cognitive tests are the next step. There are many brief cognitive tests in common use.

1) MMSE: While this widely used tool was originally designed to distinguish dementia from depression, it has been used extensively in clinical practice, epidemiologic surveys, and pharmacologic studies. The domains covered in the MMSE include orientation, short-term recall, basic language, and visuospatial construction. A standardized version has improved reliability. The MMSE is insensitive to the identification of MCI but declines at a fairly predictable rate during the progression of typical AD.

2) Montreal Cognitive Assessment (MoCA) (available at www.mocatest.org): This tool was introduced to detect mild cognitive impairment but has gained wide acceptance in a broad range of cognitive disorders. Although initially introduced as royalty-free, the creators began restricting access to those who participated in paid training sessions in 2019. Each item in the MoCA is derived from more established neuropsychologic tests and it is available in several versions and multiple languages. In addition to testing delayed recall and orientation, the language section is more comprehensive than the MMSE (phonemic fluency, sentence repetition), and executive function is tested with clock drawing, a short version of trail making test part B (connecting a sequence of alternating numbers and letters), and a 3-dimensional diagram. Attention is measured by digit span forward and backward as well as a finger-tapping exercise. A simple version of the categories test explores abstract thinking.

As part of the clinical assessment of mental status, simple bedside cognitive tests allow for measurement of decline or response to treatment of dementia. Extensive neurocognitive testing is usually reserved for younger patients who may need to apply for disability pensions or to determine whether an occupation is still feasible. Testing may also be appropriate for older patients who are still working, especially in medical, academic, and legal occupations. Unusual presentations of dementia may also benefit from neurocognitive testing and can add to the above measures when it is essential to determine if an individual with MCI is most likely to progress to dementia.

3. Laboratory tests: In all suspected cases of dementia or MCI we recommend 6 basic laboratory tests to be performed if not done recently: complete blood count (CBC), blood glucose level or glycated hemoglobin (HbA1c), serum calcium, serum thyroid-stimulating hormone, electrolytes and serum B12 levels.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and the risk of bias. Health Quality Ontario. Vitamin B12 and cognitive function: an evidence-based analysis. Ont Health Technol Assess Ser. 2013 Nov 1;13(23):1-45. eCollection 2013. Review. PubMed PMID: 24379897; PubMed Central PMCID: PMC3874776.

4. Neuroimaging: Neuroimaging is appropriate for most individuals presenting with dementia but the yield of significant abnormalities is higher if indications for neuroimaging are present (Table 12.4-5). Specific findings on imaging may help refine diagnosis. Medial temporal and hippocampal atrophy are characteristic of AD, frontotemporal atrophy suggests FTD, and atrophy of occipital and posterior parietal lobes supports the visuospatial presentation of AD. When performing computed tomography (CT) or magnetic resonance imaging (MRI) for suspected dementia, make sure to specify complex or 3 views (axial, coronal, sagittal) to obtain maximum information. In some cases a radionuclide scan may be helpful in distinguishing FTD from AD, especially where language deficits or behavioral symptoms predominate. A positron emission tomography (PET) scan with fluorodeoxyglucose (FDG) is optimal but usually not available outside the research setting. A single-photon emission computed tomography (SPECT) scan is a reasonable alternative. PET amyloid scanning is emerging as an accurate method of diagnosing AD but is not yet widely available.

5. Cerebral spinal fluid (CSF) analysis: CSF analysis for early diagnosis of AD is becoming more available. The typical findings in AD, even before the onset of dementia, include an elevated level of tau and depressed level of beta-amyloid.

6. Screening: Present evidence does not support screening for cognitive impairment or dementia in any age group.Evidence 2Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the lack of studies. Canadian Task Force on Preventive Health Care, Pottie K, Rahal R, Jaramillo A, et al. Recommendations on screening for cognitive impairment in older adults. CMAJ. 2016 Jan 5;188(1):37-46. doi: 10.1503/cmaj.141165. Epub 2015 Nov 30. PubMed PMID: 26622001; PubMed Central PMCID: PMC4695353.

ManagementTop

General Considerations

1. Education and support: Education and support for patient, caregivers, and family comprise the cornerstone of management.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and indirectness to general settings. Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14;67(9):1592-9. PubMed PMID: 17101889. Establishing the degree of risk to the individual and others is an important first step. Several items mandate urgent attention (Table 12.4-6). Some of these may be easily addressed, for example, by disabling the stove or removing guns from the house.

Support and advocacy organizations such as the Alzheimer’s Society of Canada (ASC) are extremely helpful to patients, relatives, and caregivers. The ASC website (www.alzheimer.ca) is particularly helpful and many local chapters offer educational programs and support activities. Referral to a local chapter of the ASC is suggested for all newly diagnosed individuals.

2. Driving: The issue of driving safety is important and contentious. In most provinces physicians are required to report to the Provincial Ministry of Transport individuals who have conditions that may threaten their driving safety. It may be necessary to arrange road assessments when driving safety is hard to assess in the office. If the individual has a severe dementia, the course of action is unequivocal. In individuals with MCI or early dementia the risk to driving safety is usually small but the clinical assessment can be further refined by an on-road or computer-aided test (eg, for Ontario visit the website of the Ministry of Transportation). In those with mild to moderate dementia the decision to report is made on an individual basis.

3. Future planning: It is important to consider future planning, for example, assigning powers of attorney for property and personal care, planning advance directives, and making a will. There are many initiatives that help maintain quality of life in patients with dementia. These include therapeutic and social day programs, individually tailored recreational therapies, and activities based on former hobbies and pastimes.

4. Coexisting conditions: It is important to address coexisting conditions. For example, poorly controlled endocrine and metabolic disorders may aggravate the cognitive deficits at present in an individual with dementia. Heart failure is an important contributor to cognitive deficits and optimal management of heart failure can significantly improve these manifestations. Attention is also directed towards medications that may aggravate cognitive symptoms. These include most sedatives, hypnotics, anxiolytics, and numerous medications with anticholinergic adverse effects, such as tricyclic antidepressants, antispasmodics, older antihistamines, and medications used for overactive bladder. Most narcotics also affect cognition, and many medications for diverse purposes have anticholinergic adverse effects.

Pharmacologic Therapy

Medications play a relatively minor role in the spectrum of management for dementing conditions (Table 12.4-7).

1. Cholinesterase inhibitor (ChEI) cognitive enhancers have modest efficacy at best but in some individuals they show useful improvement or stabilization of symptoms over a number of months, sometimes extending into years. For this reason, most individuals with AD, mixed dementia, DLB, or PD should be offered a trial of a ChEI for 3 to 6 months.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Buckley JS, Salpeter SR. A Risk-Benefit Assessment of Dementia Medications: Systematic Review of the Evidence. Drugs Aging. 2015 Jun;32(6):453-67. doi: 10.1007/s40266-015-0266-9. Review. PubMed PMID: 25941104. If decline continues during the trial, switching to an alternative agent is occasionally helpful. If there is no evidence of improvement or stabilization, the ChEI should be tapered before discontinuation. Balanced against the modest benefits in cognition, daily activities, and possibly behavior, these drugs are expensive and can have significant adverse effects. Gastrointestinal disturbance occurs in ~10% of patients, including nausea, anorexia, abdominal cramps, and looser bowel movements, and occasionally vomiting or severe diarrhea. Bradycardia and heart blocks develop on occasion and may result in falls and syncope. Caution is required in patients who are receiving beta-blockers or nondihydropyridine calcium channel blockers (eg, diltiazem, verapamil), as bradycardia may be precipitated. Bifascicular and trifascicular blocks are contraindications to ChEIs. Right bundle branch or left anterior fascicular blocks are not considered contraindications providing there is no atrioventricular delay. These drugs may also precipitate bronchospasm and should be used with caution in individuals with reversible airways disease. Prior to considering ChEIs, electrocardiography (ECG) is recommended, together with evaluation of history for previous peptic ulceration, gastroesophageal reflux disease, or asthma.

2. Memantine is an NMDA receptor partial agonist with modest efficacy in moderate to severe degrees of AD. It is usually prescribed together with a ChEI as their actions are possibly complementary. It is debatable whether this drug has any real benefit over donepezil alone.Evidence 5Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med. 2012 Mar 8;366(10):893-903. doi: 10.1056/NEJMoa1106668. PubMed PMID: 22397651.

Neuropsychiatric Symptoms

Neuropsychiatric symptoms in dementia are common and often progressive. Depression, apathy, anxiety, and agitation are the most prevalent features. Management should start with nonpharmacologic strategies to address the cause of the symptoms with appropriate modification of activities, communication, and environment.Evidence 6Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias. Livingston G, Kelly L, Lewis-Holmes E, et al. Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials. Br J Psychiatry. 2014 Dec;205(6):436-42. doi: 10.1192/bjp.bp.113.141119. Review. PubMed PMID: 25452601. Comorbid depression should be treated as it often compounds the severity of irritability and apathy.Evidence 7Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Shub D, Bass DM, Morgan RO, et al. Irritability and social isolation in dementia patients with and without depression. J Geriatr Psychiatry Neurol. 2011 Dec;24(4):229-34. doi: 10.1177/0891988711427039. PubMed PMID: 22228830. Caregiver education and counseling are also crucial. A thorough review of the patient’s clinical status may reveal infection, organ failure, dehydration, constipation, pain, inappropriate medications, or insomnia as reversible causes of agitation. If symptoms persist despite nonpharmacologic means, consider a trial of an antidepressant, such as citalopram.Evidence 8Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity and indirectness. Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD008191. doi: 10.1002/14651858.CD008191.pub2. Review. PubMed PMID: 21328305.  Atypical antipsychotics should be considered only when serious psychotic symptoms are present, as they are associated with an increased risk of stroke and death.Evidence 9Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and indirectness. Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003476. Review. PubMed PMID: 16437455. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005 Oct 19;294(15):1934-43. PubMed PMID: 16234500. Also see Neuropsychiatric Symptoms in Dementia.

End-of-Life Care in Dementia

Almost all causes of dementia are relentlessly progressive, and as the condition worsens decisions must be made about treatment of coexisting or superimposed illnesses. Decisions to continue or stop medications (eg, statins), offer surgical versus palliative treatment (eg, for severe osteoarthritis, symptomatic coronary artery disease), or initiate invasive care for acute infections (eg, ventilation for respiratory failure) can be very challenging. Decisions must be individualized, based wherever possible on the individual’s advance directives, and considering the prognosis in advanced dementia. For example, in nursing home residents with advanced dementia, pneumonia or a febrile episode are associated with nearly 50% mortality within 6 months, while eating problems in this population are associated with nearly 40% mortality in 6 months.Evidence 10Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009 Oct 15;361(16):1529-38. doi: 10.1056/NEJMoa0902234. PubMed PMID: 19828530; PubMed Central PMCID: PMC2778850.  One approach to weighing up the risks and benefits of planned treatments in frail individuals has been well described in the process entitled Palliative and Therapeutic Harmonization (PATH), which sets out a framework to approach decision-making in this context.Evidence 11Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Moorhouse P, Mallery LH. Palliative and therapeutic harmonization: a model for appropriate decision-making in frail older adults. J Am Geriatr Soc. 2012 Dec;60(12):2326-32. doi: 10.1111/j.1532-5415.2012.04210.x. Epub 2012 Oct 30. PubMed PMID: 23110462.

Specialist Clinic Management

Referral to a specialist clinic is needed when the diagnosis is unclear or if help with management is needed. Specialist clinics adopt a multidisciplinary approach and usually provide management support. Future planning, home and driving safety, community outreach, and follow-up are all parts of dementia care, as are pharmacotherapy and ultimately end-of-life care. Counseling, education, and caregiver support have been shown to significantly delay nursing home placement and reduce caregiver burnout.Evidence 12Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and indirectness. Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14;67(9):1592-9. PubMed PMID: 17101889. Specialist clinics may also provide access to research studies.

PreventionTop

Reduction of vascular risk factors appears to be the most promising approach to preventing dementia. For example, if one can delay or prevent strokes, it may be possible to delay or prevent the onset of mixed or vascular dementias. The only trial which shows this conclusively is the SYST-EUR study, which demonstrated that treatment of moderately severe systolic hypertension reduced the risk of dementia of all types by 50% over 5 years.Evidence 13Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias. Forette F, Seux ML, Staessen JA, et al; Systolic Hypertension in Europe Investigators. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002 Oct 14;162(18):2046-52. Erratum in: Arch Intern Med. 2003 Jan 27;163(2):241. PubMed PMID: 12374512. Epidemiologic studies suggest that those who are more active physically and mentally are less likely to experience dementia, but strong evidence for such claims is lacking. Restriction of heavy (but not moderate) alcohol use and striving for more education are some of the measures that might be helpful. There are some encouraging signs that the prevalence of dementia is beginning to decline in North America and Europe, which is thought to be due to more aggressive management of vascular risk factors.

TablesTop

Table 12.4-1. Diagnostic criteria for probable Alzheimer disease

1. Insidious onset

2. Clear-cut history of worsening

3. Initial and prominent cognitive deficits on history and examination with either amnestic or nonamnestic presentation

Variants

Language variant: Progressive nonfluent aphasia

Visuospatial variant: Posterior cortical atrophy

Frontal executive variant: Frontal atrophy

AD is considered improbable in case of:

– Substantial evidence of cerebrovascular disease

– Core features of dementia with Lewy body present (complex visual hallucinations, early parkinsonism, fluctuating cognition)

– Prominent features of behavioral variant frontotemporal dementia (disinhibition, apathy, loss of empathy, hyperorality, executive dysfunction, perseverative behavior)

– Prominent features of semantic dementia or primary progressive aphasia

– Other neurologic or nonneurologic illness or drugs

Table 12.4-2. Diagnostic criteria for frontotemporal dementia

Early and progressive change in:

Personality: Difficulty modulating behavior, inappropriate responses and activity (eg, disinhibition, apathy, poor insight and judgment, self-neglect)

or

Language: Expression, severe naming difficulty or meaning (progressive expressive aphasia) contraction of language

Table 12.4-3. Diagnostic criteria for dementia with Lewy bodies

Dementia plus:

1) Core features:

– Fluctuating cognition

– Well-formed visual hallucinations

– Spontaneous parkinsonism

2) Suggestive features:

– REM sleep disorder

– Severe neuroleptic sensitivity

REM, rapid eye movement.

Table 12.4-4. Vascular cognitive impairment: probable vascular dementia

1. Dementia is present

2. Deficits in daily function are independent of the motor/sensory sequelae of the vascular event

3. Cognitive impairment and imaging evidence of cerebrovascular disease and:

1) A clear temporal relationship between a vascular event (eg, clinical stroke) and onset of cognitive deficits; or

2) A clear relationship in the severity and pattern of cognitive impairment and presence of diffuse subcortical cerebrovascular disease

4. No history of gradually progressive cognitive deficits before or after stroke that suggests the presence of a nonvascular neurodegenerative disorder

Table 12.4-5. Indications for neuroimaging

– Age <65 years

– Relatively short clinical history

– Focal neurologic symptoms

– Focal neurologic signs

– History of head trauma

– Anticoagulants or bleeding diathesis

– Malignancy that might metastasize to brain

– Atypical features (not suggesting Alzheimer disease)

– In cases where finding of cerebrovascular disease would significantly influence management

Table 12.4-6. Clinically alarming features (red flags) in patients with cognitive decline

Red flags

Examples/clues

Fire

Smoking, kitchen safety

Wandering

Increased unexplained time away from home, leaving home at night

Inability to summon help

Using telephone, understanding emergency response system, eg, Lifeline

Risk of falls/injuries

Abnormal gait, history of falls, bruises/injuries

Risk to others

Potential violence to spouse, caregiver, others, guns in home

Motor vehicle driving

Damage to vehicle, impaired judgment when driving

Narrow therapeutic index medications

Where missed or duplicated doses may have serious consequences (eg, insulin, oral hypoglycemic agents, anticoagulants, anticonvulsants, lithium, digoxin)

Table 12.4-7. Medications for dementia (Alzheimer disease, mixed, dementia with Lewy bodies)

Starting and maximum doses

Dosage

Comments

Donepezil

Start: 5 mg daily (2.5 mg for very frail persons)

Max: 10 mg daily

Increase to 10 mg daily after 4 weeks

(in the very frail 2.5 mg daily for 2 weeks then 5 mg daily for 4 weeks; 10 mg later if tolerated)

GI adverse effects in ~10% of patients, syncope, falls, worsening cardiac conduction (avoid with severe bradycardia, heart blocks) night cramps, can disturb sleep

Galantamine ER

Start: 8 mg daily

Max: 32 mg daily

Increase to 16 mg daily after 4 weeks, then 24 mg daily after another 4 weeks if tolerated

GI adverse effects in ~10%, syncope, falls, worsening cardiac conduction (avoid with severe bradycardia, heart blocks)

 

Rivastigmine

Oral

Start: 1.5 mg bid (1.5 mg daily for very frail persons)

Max: 6 mg bid

Increase to 3 mg bid after 4 weeks, 4.5 mg bid after another 4 weeks, then 6 mg bid after another 4 weeks if tolerated (in the very frail, 1.5 mg daily for 2 weeks, then 1.5 mg bid for 4 weeks, then 3 mg bid for 4 weeks, and increments of 1.5 mg bid each 4 weeks)

GI adverse effects in ~10%, syncope, falls, worsening cardiac conduction (avoid with severe bradycardia, heart blocks)

 

Transdermal patch

Start: Exelon patch 5 (4.6 mg every 24 hours)

Max: Exelon patch 15 (13.3 mg every 24 hours)

Starting dose patch 5, increase to patch 10 after 4 weeks

Transcutaneous patch delivers rivastigmine with much lower incidence of GI adverse effects

Memantine

Start: 5 mg daily

Max: 10 mg bid

After 1 week increase to 5 mg bid; after 1 more week 10 mg every morning, 5 mg every afternoon; after 1 more week 10 mg bid

Occasional headache, dizziness

Donepezil, galantamine, rivastigmine are cholinesterase inhibitors.

Memantine is an NMDA receptor agonist.

bid, 2 times a day; ER, extended release; GI, gastrointestinal.

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