For many older patients with cognitive complaints, their evaluation, diagnosis, and management may be effectively completed within a primary care setting. If available, utilization of multidisciplinary team members from nursing, social work, psychology, and/or pharmacy can greatly aid a primary care physician in the diagnosis and management of patients with cognitive concerns. A smaller subset of patients will need more in-depth neuropsychological assessment and clinical evaluation from a dementia specialist. The NIA-AA clinical diagnostic criteria for dementia, AD, and MCI (see Tables 66-1 and 66-2) were designed to be used across all clinical settings, including primary care, specialty clinics, and long-term care. The clinical diagnoses of MCI and dementia are primarily ascertained through completion of a focused interview with the patient and an informant who knows the patient well, a thorough review of the patient’s medical history and medication use, a comprehensive physical examination, a formal assessment of cognitive function, basic laboratory tests, and neuroimaging (Table 66-3). While the differential diagnosis for AD is extensive (Table 66-4), a systematic approach to dementia diagnosis can help primary care clinicians identify common confounding medical and psychiatric conditions and medications that can adversely affect cognition. In addition, a structured evaluation may facilitate accurate diagnosis of the most common causes of dementia—AD and AD mixed with vascular dementia as well as predementia syndromes such as MCI. Integrating various established diagnostic criteria, Figure 66-3 shows a primary care diagnostic algorithm developed to guide clinicians in their assessment of patients with cognitive complaints.
TABLE 66-3EVALUATION OF THE PATIENT WITH COGNITIVE CONCERNS |Favorite Table|Download (.pdf) TABLE 66-3 EVALUATION OF THE PATIENT WITH COGNITIVE CONCERNS
History of cognitive changes
Primary symptom(s) at onset (memory loss, language/spelling errors, impaired reasoning, difficulties in multitasking, personality changes, etc)
Date of onset and time course of cognitive decline (gradually progressive, stepwise, fluctuating, abrupt, rapidly progressive, etc) and whether or not it was associated with delirium
Past and present function at higher level tasks (including tasks at work, hobbies, daily household chores including instrumental activities of daily living [IADLs])
Safety concerns (medication management, driving, kitchen safety, use of firearms or heavy equipment, wandering, financial scams, etc)
Other associated symptoms (depression, tremor, frequent falls, visual hallucinations, stroke and/or transient ischemic attack symptoms, ataxia, urinary incontinence, agitation, personality changes, etc)
Past medical and psychiatric history
Vascular risk factors (including how well they have been controlled over time)
Strokes and/or transient ischemic attacks (assess whether cerebrovascular event was associated with onset of cognitive symptoms)
Atrial fibrillation, carotid artery disease, patent foramen ovale, and/or other risk factors for stroke
Coronary artery bypass surgery (assess whether surgery was associated with onset of cognitive symptoms)
Other major central nervous system (CNS) event (traumatic brain injury with loss of consciousness, anoxic brain injury, postoperative cognitive dysfunction, etc)
Hearing and/or vision loss
Obstructive sleep apnea (including how well it is treated with continuous positive airway pressure [CPAP] or other modalities)
Alcohol or other substance abuse
Depression, anxiety, posttraumatic stress disorder, or other psychiatric illness
Parkinson disease, parkinsonism, amyotrophic lateral sclerosis, or multiple sclerosis
History of malignancy with or without prior treatment with chemotherapy
Prescription and nonprescription medications and supplements (especially those with anticholinergic or sedating side effects)
Timing of onset of cognitive symptoms with medication/supplement initiation or dose change
Family, friends, and other social support
Use of community resources (including home aides, senior centers, meal services, etc)
Educational history (including formal years of education and/or technical training, any interruption in schooling or repeated grades, any suspected or diagnosed learning disabilities or attention deficit disorder, etc)
Work history (including types of responsibilities associated with occupation)
Military history (including exposure to combat or blast injuries)
Hobbies and other daily activities
Substance use history (including any prior history of heavy alcohol use)
History of AD or other dementias (including age of onset of symptoms in affected family members)
History of other neurodegenerative disorders, strokes, psychiatric illnesses, etc
General appearance (attention, comprehension, cooperation, personal hygiene and grooming, social appropriateness, psychomotor slowing, word-finding difficulties)
Mental status (behavior, attitude, mood, affect, insight, judgment, thought content, thought process, speech, language)
Cranial nerves (facial symmetry, visual acuity, pupillary responses, eye movements, visual fields, hearing impairment)
Motor function and integration (strength, tone, cogwheeling, simulation of motor actions to test for apraxia)
Sensory function and integration (sensation to light touch, identification by touch of an object placed in the hand or a number written on the hand, ability to perceive simultaneous bilateral tactile stimuli)
Coordination (rapid alternating movements, finger-to-nose testing, heel-shin testing)
Deep tendon reflexes
Screening Cognitive Tests (time to administer)
Mini Mental State Examination (MMSE) (5–10 min)
Montreal Cognitive Assessment (MoCA) (10 min)
Saint Louis University Mental Status (SLUMS) Examination (5–10 min)
Mini-Cog (3 min)
Memory Impairment Screen (MIS) (3–4 min)
General Practitioner Assessment of Cognition (GPCOG) (4 min)
Geriatric Depression Scale—Short Form (GDS-SF) (5–7 min—may be self-administered)
Eight-Item Interview to Differentiate Aging and Dementia (AD8) (3 min)
GPCOG Informant Questionnaire (2 min)
Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (10–15 min)
Vitamin B12, thyroid-stimulating hormone (TSH), 25-OH vitamin D, complete blood count, glucose, blood urea nitrogen and creatinine, basic metabolic profile, liver enzymes
Noncontrast head CT
TABLE 66-4DIFFERENTIAL DIAGNOSIS FOR ALZHEIMER DISEASE |Favorite Table|Download (.pdf) TABLE 66-4 DIFFERENTIAL DIAGNOSIS FOR ALZHEIMER DISEASE
|Depression ||Lewy body dementia |
|Adverse medication effects ||Vascular dementia/vascular cognitive impairment |
|Delirium ||Frontotemporal dementia |
|Acute alcohol intoxication ||Parkinson disease dementia |
|Substance use disorders ||Progressive supranuclear palsy |
|Obstructive sleep apnea ||Corticobasal degeneration |
|Other sleep disorders ||Prion-related diseases (Creutzfeldt-Jakob, bovine spongiform encephalopathy) |
|Chronic hypoxia and/or hypercapnia ||Normal pressure hydrocephalus (NPH) |
|Recurrent hypoglycemia ||Huntington disease |
|Thyroid diseases ||Alcohol-related dementia |
|Other metabolic-endocrine disorders ||Wernicke-Korsakoff syndrome |
|Vitamins B1 (thiamine), B12, and/or D deficiencies ||Traumatic brain injury |
|Uremia ||Chronic traumatic encephalopathy (CTE) |
|Hepatic encephalopathy ||Mass lesions (neoplasms, benign tumors, hematomas) |
|Environmental toxicity (lead, mercury, polychlorinated biphenyls [PCBs], dioxins, etc) ||Central nervous system rheumatologic/autoimmune disorders (systemic lupus erythematosus, sarcoidosis, vasculitis, multiple sclerosis, etc) |
|Lyme disease ||Paraneoplastic syndromes |
|HIV-associated neurocognitive disorders (HAND) ||Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) |
|Progressive multifocal leukoencephalopathy (PML) ||Carotid artery disease |
|Chronic meningitis/encephalitis ||Postoperative cognitive dysfunction |
|Neurosyphilis ||Seizure disorder |
Algorithm for the clinical diagnosis of Alzheimer disease.
Identification of a cognitive concern is the first step in the evaluation. While early cognitive changes in some patients may be readily identified by the individuals themselves, their families, and/or their clinicians, such symptoms may not be as apparent in other patients due to a variety of factors, including poor insight, attribution of such changes to normal aging, cultural views of dementia, or lack of corroborative history from others. Whether all older adults should undergo routine screening for dementia remains controversial. The United States Preventive Services Task Force recommends against routine screening for dementia in asymptomatic older adults based on insufficient evidence that such widespread screening impacts individual or societal outcomes. However, the US Medicare Annual Wellness Visit requires that clinicians assess cognitive function by “direct observation,” although no cognitive screening tool is endorsed. In an effort to operationalize the Medicare Annual Wellness Visit requirements, the Alzheimer’s Association recommends using self-reported memory concerns, clinician observations, or concerns from a person who knows the patient well to trigger a formal memory assessment. Screening questions such as “Does your memory bother you?” or “Do you think your memory is worse than others of your age?” also may be used to determine which older patients need a formal evaluation of cognitive performance. Identifying memory concerns through self-report or screening questions may reduce the number of unnecessary formal cognitive screening tests administered to asymptomatic adults at low risk for dementia. However, individuals without a close informant may need structured cognitive tests to identify memory concerns. When a cognitive concern is identified, a separate clinic visit should be arranged to investigate the underlying cause (see Figure 66-3, Table 66-3).
Within a dedicated primary care clinic visit, an optimal cognitive assessment includes gathering information not only from the patient’s perspective, but also independently in a separate interview from an informant who knows the patient well. Depending on available time and resources, an independent informant interview may be accomplished through utilizing a variety of health care team members, such as social workers, medical assistants, nurses, or psychologists to conduct a brief structured informant interview or a full detailed assessment. Important historical elements include establishing when the cognitive symptoms began and the very first symptoms noted (such as problems with memory, language, executive function, apraxia, or personality changes). A careful delineation of the time course of progression will narrow the differential diagnosis and will help identify whether there are multiple contributing factors or one underlying process. Frequently, an inciting event that disrupts coping skills, such as a hospitalization or the death of a spouse, will draw the attention of family members to a patient’s memory problems. The family may give a history of an acute onset of memory impairment following the inciting event, but careful questioning may identify cognitive problems preceding that time period and point to a gradually progressive course.
A key component to the interview is establishing the patient’s baseline cognitive and functional performance, taking into account past educational opportunities, estimated baseline intellectual function, occupational history, and prior established skills and abilities. Understanding the patient’s baseline function will put neuropsychological test results into context in order to prevent over- or underdiagnosing dementia in patients who present with cognitive concerns. Changes in the person’s ability to carry out tasks related to their occupation, hobbies, household management, and other volunteer activities should then be ascertained.
There are common reversible causes of cognitive dysfunction that next should be addressed. One of the first steps should be a careful review of prescription and nonprescription medications. Drugs with known anticholinergic properties (such as antihistamines, tricyclic antidepressants, bladder antispasmodic agents, etc) or sedating side effects (such as high-dose gabapentin, other antiepileptic medications, narcotic analgesics, benzodiazepines, sleeping aids, etc) should be carefully reviewed to see if the benefit of the offending medication outweighs the adverse cognitive effects. Patients should be included in shared decision making with any medication adjustments as the value placed on various symptoms is likely to differ between individuals.
Clinicians should carefully evaluate their older patients for depression, anxiety, or other mood disorders that can affect cognitive performance. Depression may be a prodromal syndrome prior to dementia onset, but also commonly co-occurs with this syndrome. Pointed questions assessing for changes in sleep duration and/or quality, interest in activities, feelings of guilt, loss of energy, impaired concentration, changes in appetite, psychomotor slowing, and suicidal thoughts should be assessed. A brief screening tool such as the Geriatric Depression Scale (GDS) can be administered by a health care team member or self-administered while the patient is waiting for the clinician. Older patients with depression frequently complain of problems with poor concentration and forgetfulness and may perform poorly on tests of attention, speed of processing, and memory. In such patients, it is important to differentiate a loss of interest related to depression from a lack of initiative due to a neurodegenerative disorder. Treating depression and anxiety may lead to improvements in cognitive performance as well as mood.
Hearing loss may mimic cognitive dysfunction as patients who cannot hear well may not be able to properly encode new information from conversations or other auditory-received information. Questions on hearing loss symptoms and use and fit of any prescribed hearing aids can alert the provider as to whether hearing loss is contributing to cognitive symptoms or if further hearing evaluation is needed (see Chapter 39 for approach to screening for hearing loss).
A careful assessment of alcohol use should be completed in all patients, especially if cognitive performance varies widely from visit to visit or if the patient lives alone. Risk for obstructive sleep apnea should be assessed with several screening questions assessing the patient’s snoring, witnessed apneic episodes, excessive daytime sleepiness, or nonrestorative sleep. In patients with diagnosed sleep apnea, their ability to effectively and regularly use their continuous positive airway pressure (CPAP) device should be assessed and any difficulties should be reported to the sleep medicine and/or respiratory therapy team to seek out other mask options for better fit and tolerance. Obstructive sleep apnea with its related hypoxia can cause profound effects on cognition.
Vascular disease may contribute to cognitive impairment through a variety of mechanisms. In addition to stroke causing acute cognitive decline, chronic low cerebral blood flow leading to subclinical hypoperfusion may also contribute to cognitive impairment and AD. Thus, a careful assessment of vascular risk factors should be completed to make sure they are well treated. Carotid bruits or a history of sudden cognitive changes should prompt work-up for cerebrovascular disease with neuroimaging (computed tomography [CT] or preferably magnetic resonance imaging [MRI]) and either carotid ultrasound or magnetic resonance angiogram (MRA).
Delirium is associated with an acute or subacute onset of fluctuating cognitive dysfunction and may be caused by a wide variety of medical conditions and medications. In patients with delirium, a careful history frequently can tease out the temporal relationship between the onset of potentially reversible cognitive symptoms and contributing underlying medical problems or medications. Patients who have had a significant medial illness may exhibit signs of delirium for weeks to months following the inciting illness. Care should be made to avoid making a diagnosis of dementia in the presence of a resolving delirium. Since dementia is a risk factor for delirium, however, the presence of a delirium may suggest an underlying neurodegenerative disorder.
Additional information on safety should be obtained, including inquiries on medication management, driving, kitchen safety, use of firearms or heavy equipment or power tools, wandering, and susceptibility to financial scams. A review of systems should include questions on depression, tremors, falls, visual hallucinations, symptoms of stroke or transient ischemic attack, ataxia, dysphagia, urinary incontinence, waxing and waning level of consciousness, agitation, and personality changes.
The patient’s past medical history should be reviewed for medical and psychiatric conditions affecting cognition, including cardiovascular and cerebrovascular disease and associated risk factors, surgical procedures including coronary artery bypass surgery, significant hearing loss, depression, Parkinson disease, traumatic brain injury, seizures, and/or heavy alcohol use. A thorough medication review should be conducted to assess all prescription and nonprescription medications and the association of any medication initiation and/or dose adjustment with changes in cognitive symptoms. Patients should be encouraged to bring in all pill bottles to the clinic visit. The social history should assess the patient’s education and occupational baseline, their social support network, and their use of community resources. An accurate assessment of prior or current alcohol or illicit drug use and a sexual history with special attention to sexually transmitted disease (notably syphilis and HIV) risk factors are critical to a correct diagnosis. An assessment of family history of dementia should include age of onset and time course of any symptoms of family members with memory loss.
The physical examination should include assessment of general appearance and a mental status examination (see Table 66-3). Careful observation upon interviewing a patient can provide rich information as to their ability to care for themselves, their organizational ability, their ability to provide detail within their conversation, and their comprehension of posed questions and the appropriateness of their response. Ears should be checked for any cerumen accumulation and/or hearing loss. A neurologic examination should screen for focal deficits, gaze palsies, increased muscle tone, cogwheeling, tremors, and ataxia. A detailed review of a comprehensive mental status and neurologic examination in older adults is described in Chapter 11. Cardiac arrhythmias, carotid bruits, or abdominal or femoral bruits may suggest a vascular contribution. The remainder of the physical examination should focus on ascertaining any major medical conditions that could have significant cognitive effects, such as hypoxia or significant active infection.
While there is no consensus as to which is the best cognitive screening tool, there are a variety of cognitive screening tests that have been validated in a primary care setting. Clinicians should identify several with which they are comfortable so that they can be used consistently over time with their patient population. The Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Saint Louis University Mental Status Examination (SLUMS) have been widely used in primary care settings. The Alzheimer’s Association recommends use of the General Practitioner Assessment of Cognition (GPCOG), the Mini-Cog, or the Memory Impairment Screen (MIS) for cognitive screening related to the Medicare Annual Wellness Visit, as these tests take less than 5 minutes to administer, have good psychometric properties, and can be administered by a variety of health care team members. Informant assessment of changes in patient performance may include the GPCOG informant questionnaire, the Eight-Item Interview to Differentiate Aging and Dementia (AD8), or the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (see Table 66-3). If time and resources allow, additional interview time with an informant may identify specific areas of safety concerns and help tailor the management plan.
In adults with high baseline cognitive function, these screening tests may be normal in the presence of obvious functional impairment necessitating referral to a neuropsychologist for more detailed cognitive testing. In individuals with lower educational levels or learning disabilities, cognitive screening tests may suggest impairment, but the history may not suggest any changes in functional status. Thus, it is critical to use age- and education-adjusted norms, and integrate historical information on baseline function to decide if further neuropsychological testing is warranted or if abnormal testing actually reflects the patient’s baseline cognitive performance.
Laboratory data can assist in identifying factors that may be contributing to cognitive decline. Rarely do these factors alone account for the overall cognitive changes that lead to the presentation of a patient with significant memory loss. Nevertheless, treating such factors may improve cognitive symptoms in patients with pronounced laboratory abnormalities, numerous comorbid illnesses, or an underlying neurodegenerative process. Recommended laboratory tests include vitamin B12, folate, thyroid-stimulating hormone (TSH), electrolytes, complete blood count, liver enzymes, and 25-OH vitamin D. If symptoms are atypical or if there are specific risk factors, then an HIV test or serologic test for syphilis may be performed. In patients with assumed heavy alcohol use, thiamine (vitamin B1) levels should be checked. In some European countries, routine assessment of cerebrospinal fluid (CSF) for β-amyloid and tau levels is done as part of the clinical evaluation. While CSF β-amyloid and tau levels may increase diagnostic accuracy of MCI and dementia due to AD, in general they are not recommended for widespread clinical practice as in most cases they do not change a patient’s management plan. CSF collection may be used in memory specialty clinics, though, to differentiate between different dementias, including Creutzfeldt-Jakob disease, normal pressure hydrocephalus (NPH), or other less-common causes of neurodegeneration (see Table 66-4). Genetic testing for APOE ε4 genotype is not recommended in routine clinical practice. Testing for PSEN1, PSEN2, or APP genes should be reserved for specialists evaluating cases in which there is a suspicion for familial AD.
In patients with documented cognitive impairment, it is recommended that either a CT or MRI scan of the brain be obtained. If neuroimaging was obtained for another indication prior to the onset of cognitive symptoms, in most cases the patient should be reimaged. Typical findings for AD on neuroimaging can range from a fairly normal scan to focal or diffuse cerebral atrophy. A CT of the head without contrast is usually sufficient to screen for significant cerebrovascular disease, brain tumors, subdural hematoma, or NPH. MRI can provide more information if lacunar infarcts are suspected. MRA may be helpful in identifying significant stenosis that could cause hypoperfusion. In persons with suspected seizure disorder or Creutzfeldt-Jakob disease, an electroencephalogram (EEG) may be considered. Use of FDG positron emission tomography (PET) and amyloid PET imaging to differentiate frontotemporal dementia from AD should be reserved for specialty clinic use. Tau PET imaging is a novel research tool that is not yet approved for clinical practice.
Once a cognitive concern is recognized and delirium is ruled out, the clinician should identify and document any impaired cognitive domains (such as memory, executive function, language, or visuospatial skills) on cognitive testing and any functional loss in the individual’s daily activities. Each potentially reversible cause of cognitive impairment should be outlined (ie, medication side effects, alcohol, sleep apnea, depression, or other medical comorbidities) and a plan to address these conditions should be developed. Objective cognitive impairment in the context of a supportive clinical history plus a decline in the individual’s daily functional abilities are key elements necessary to differentiate normal cognitive aging and subjective cognitive decline from MCI and dementia. With normal aging, individuals may experience a decline in mental processing speed and may have more difficulty learning new material, but these cognitive changes should not affect their usual function within their daily activities. For example, a healthy older adult may have more difficulty recalling an acquaintance’s name or learning a new computer program, but their cognitive testing should be normal and daily functional activities should remain intact. Subjective cognitive decline (SCD) is a newer term used primarily in research settings to broadly describe symptoms within a pre-MCI stage of neurodegeneration. SCD is currently defined as a self-identified persistent decline in cognitive capacity compared with the individual’s previous normal status in a person who still performs in the normal range on standardized cognitive tests. An example would be a business manager with normal performance on cognitive testing who has noticed a subjective decline in her efficiency in managing numerous projects simultaneously despite maintaining a similar work load for many years. It is not yet known what percentage of patients presenting with SCD progress on to MCI and eventually AD. However, identification of patients with SCD allows clinicians to complete a thorough evaluation for other medical, psychological, and medication factors that could contribute to cognitive decline. Patients with SCD should be screened for cognitive dysfunction annually to evaluate for objective evidence of a decline in cognitive performance.
Once a person with SCD develops deficits in at least one cognitive domain, they may meet criteria for MCI (see Table 66-2), a symptomatic predementia syndrome noted in up to 15% to 20% of older adults. Individuals with MCI may present with cognitive complaints and describe a variety of methods they use to compensate for these cognitive changes, such as increasing use of lists, calendars, alarms, and other reminders. They maintain their level of function, but are less efficient in doing so. For example, a cabinetmaker who demonstrates impairment in executive function on testing may complain that in order to complete a cabinet work order with his same level of quality workmanship, it now takes him 2 to 3 weeks, whereas a few years ago he could complete such an order in 1 week. Once an individual’s cognitive impairment progresses to the point that they can no longer maintain their baseline level of function, they may meet criteria for dementia. In the previous example, as the cabinetmaker’s cognition declines he may no longer be able complete a cabinet order at all or may finish it with poorer-quality workmanship. At that point he may have progressed to a dementia.
Approximately 12% to 15% of persons with MCI will progress each year to AD or other forms of dementia. MCI patients who have impairment in memory performance (single-domain amnestic MCI) or in memory plus another cognitive area (multidomain amnestic MCI) are more likely to progress to AD. Older individuals with nonamnestic MCI may be more likely to progress to other forms of dementia, such as frontotemporal dementia, dementia with Lewy bodies, or vascular dementia. Once a diagnosis of dementia is suspected, the clinician must differentiate between various causes of dementia. AD is the most common form of dementia in the United States, accounting for 50% to 90% of all dementia cases. Dementia with Lewy bodies, vascular dementia, and frontotemporal dementia are other common forms of dementia (Table 66-5). Details of the clinical and pathologic features of these dementias are covered in Chapter 68. Differentiating AD from other causes of memory loss can help clinicians choose effective therapies, anticipate behavior changes and other potential complications, and provide patients and caregivers information on prognosis.
TABLE 66-5CLINICAL FEATURES OF COMMON DEMENTIAS |Favorite Table|Download (.pdf) TABLE 66-5 CLINICAL FEATURES OF COMMON DEMENTIAS
|TYPE OF DEMENTIA ||ALZHEIMER DISEASE ||VASCULAR DEMENTIA ||DEMENTIA WITH LEWY BODIES ||FRONTOTEMPORAL DEMENTIA |
|MUST FIRST MEET DIAGNOSTIC CRITERIA FOR DEMENTIA (SEE TABLE 66-1) |
|Typical Course ||Insidious onset and gradually progressive ||Acute onset of cognitive impairment with some stabilization (if only one vascular event) and/or stepwise deterioration (if multiple infarcts) ||Progressive cognitive decline with fluctuating cognition, attention, and alertness ||Insidious onset and gradually progressive |
|Cognitive Symptoms || |
Memory is the most commonly affected cognitive domain
May also have impairments in executive function, language, and/or visuospatial skills
|Various cognitive domains may be affected depending on the location of the clinical stroke(s) and/or severe subcortical cerebrovascular disease || |
Cognitive symptoms may fluctuate
May have prominent impairment in visuospatial ability, attention, and/or executive function
Will have early behavioral disinhibition and apathy (frontal lobe predominance) or early prominent language abnormalities (temporal lobe predominance)
Deficits are chiefly noted in executive tasks with relative sparing of memory and visuospatial skills
|Other Associated Symptoms/Signs ||Some patients may have agitation and/or behavioral changes || |
May or may not have focal neurologic signs on examination
Should have evidence of relevant cerebrovascular disease by brain imaging
|May have recurrent well-formed visual hallucinations (usually people or animals), parkinsonism (including tremor, rigidity, and postural instability), recurrent falls and syncope, rapid eye movement (REM) sleep behavior disorder, neuroleptic sensitivity, and/or delusions ||In behavioral variant frontotemporal dementia, may have early behavioral disinhibition, apathy, loss of empathy, perseverative behaviors, and hyperorality |
If a patient does not meet the criteria for AD yet clinical suspicion remains, the clinician may consider obtaining more detailed neuropsychological testing or repeating screening cognitive testing in 6 to 12 months to clarify the diagnosis as the symptoms become more apparent. Persons with suspected MCI should be reassessed on an annual basis to evaluate for progression to dementia. If the symptoms or course of the disease are atypical for AD, the level of functional decline is out of proportion to neuropsychological testing results, or if there are significant behavioral issues that need to be addressed, then referral to a geriatrician, neurologist, or psychiatrist with expertise in dementia is recommended.
Novel biomarkers are continually being investigated for use in the diagnosis of AD and other types of dementia, as well as in identifying predementia syndromes. Many of these tools are still used chiefly in research settings, but are being studied to evaluate their potential role in clinical practice. Current investigations are focusing on specific neuroimaging modalities and biomarkers (including blood and CSF) with strong relationships to clinically relevant outcomes that could be used not only for diagnosis of dementia, but also for identifying asymptomatic persons at risk for cognitive decline. Neuroimaging modalities have shown great promise in documenting not only the late effects of neuronal damage in AD (regional and global cerebral atrophy), but also in identifying preclinical pathology (such as in vivo amyloid and tau imaging on PET) and the functional consequences of such pathology (such as changes in activation patterns on functional MRI or glucose uptake on FDG-PET). CSF levels of Aβ and tau have been shown to predict risk for progression to AD in older adults and persons with MCI. With the recent advances in the safety and acceptability of lumbar punctures, CSF markers may eventually find their way into the widespread clinical diagnostic work-up of preclinical AD. Identification of reliable blood biomarkers has been difficult due to extensive protein binding of Aβ in the periphery. Future research is focusing on how novel biomarkers may be used in combination with cognitive tests to identify which individuals are at greatest risk for AD, who would benefit most from preventive therapies, and how effective these therapies are in modifying the underlying disease process in asymptomatic and symptomatic individuals.