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Diagnostiek van dementie in de huisartsenpraktijkPublished by: ACHG | Expertisecentrum Dementie VlaanderenLast published: 2020Diagnostic de la démence en médecine généralePublished by: ACHG | Expertisecentrum Dementie VlaanderenLast published: 2020

The diagnosis of dementia is first considered by comparing the patient's current level of cognitive and functional capabilities with their premorbid or "baseline" level.[1] If a significant decline is noted, then a diagnosis of dementia can be considered by means of history, cognitive examination, physical exam, laboratory tests, and neuroimaging.[23][62]​​[63][64]​ It is important to include a review of medication, as some medicines may adversely affect cognitive function.[23]

History

The patient, family, caregivers, and other knowledgeable sources should be interviewed to discover changes in cognition, function, personality, language skills, and behavior. An insidious onset with a slow (months to years) progressive course is consistent with a degenerative process.[65]

An abrupt change, stepwise decline, or a gradual cognitive decline after one or more clinical events such as stroke is suggestive of a vascular-type cause.[65] However, minor strokes are often unrecognized. An acute (days to weeks) or subacute (weeks to months) course may suggest the presence of an infection, a metabolic disorder, an expanding brain lesion, the effects of drugs, stroke, or hydrocephalus. Creutzfeldt-Jakob disease can also be considered.[30] Rapid (hours to days) deterioration in function suggests an acute confusional state or delirium.[65]

Any changes in the ability to manage activities of daily living (eating, bathing, dressing, toileting, transferring [i.e., walking], and continence) or instrumental activities of daily living (doing housework, cooking, cleaning, shopping, managing funds, managing drugs, use of telephone, and transportation) provide important clues in diagnosing and classifying the illness.[66] An overall deterioration in all areas may point to a diffuse degenerative process such as Alzheimer disease, whereas a disproportionate decline in one area may suggest a more focal cause such as a tumor, stroke, or frontal dementias.

Family history, drug use, past medical history of systemic illness, or risk factors for stroke (previous history of stroke, transient ischemic attacks, hypertension, coronary artery disease, and atrial fibrillation) may be present. Systolic blood pressure ≥130 mmHg at age 50, below the conventional ≥140 mmHg threshold used to define hypertension, is associated with an increased risk of dementia, independent of cardiovascular disease.[67] A detailed assessment of alcohol use is important, particularly in older patients with mild cognitive impairment.[68]

An inquiry into a history of Parkinson disease is important as dementia is not uncommon in these patients, with a prevalence rate of about 80% after a disease duration of 10 years or longer.[69]

Some patients with vascular dementia have transient neurologic symptoms, a history of gait abnormalities, and incontinence at the time of initial assessment.

Patients with normal-pressure hydrocephalus (NPH) may describe pronounced gait disturbances accompanied by urinary incontinence and cognitive decline.[70][71][72]

Cognitive examination

Cognitive screening is recommended for older people with history of delirium, depression, diabetes, Parkinson disease, or recent unexplained functional losses.[27][73] The US Preventive Services Task Force found insufficient evidence to assess the balance of benefit versus harm for asymptomatic, community-dwelling adults ≥65 years.[74]

Mini-Mental State Examination

Folstein Mini-Mental State Examination (MMSE) is still the most widely used cognitive screening test.[75] A score of <24 out of a possible 30 points is widely accepted to indicate an abnormal result. However, others have suggested that a cut-off of <21 indicates an increased probability of cognitive impairment, whereas a score of ≥25 reduces the probability of cognitive impairment. Intermediate scores between 21 and 25 are less useful in determining the probability of the disease.[11] Patients with scores between 21 and 25 can be considered for reevaluation in 3 to 6 months.

MMSE is sometimes not sensitive enough to detect mild cognitive impairment (MCI).[76] These patients are often younger and have a high educational level. In addition, the MMSE lacks the ability to capture progressive decline fully in severe dementias, as well as impairments caused by focal neurologic lesions.[77][78] For these reasons cognitive examination should always be correlated with history and decline from baseline level of functioning.[79][80][81] The visual association test (VAT) has shown substantial incremental value for identifying those at increased risk for developing dementia, in patients with a small decline on the MMSE over a 2-year period.[82]

Alternative cognitive screening tests

Although many other scales, such as the Alzheimer’s Disease Assessment Scale-Cognitive Section (ADAS-Cog), the Mattis Dementia Rating Scale (MDRS), the Montreal Cognitive Assessment (MoCA), or the AD-8 questionnaire have been developed as screening tools for patients with cognitive impairment, a review indicates that no one scale is superior to the others in terms of diagnostic accuracy.[83] Cochrane reviews found that there is insufficient evidence to recommend the Mini-Cog as a screening tool for dementia in either the primary or secondary care settings.​[84][85]​​​​​​​​​

The use of standardized functional assessment questionnaires to augment cognitive testing will help differentiate patients with early dementia from patients with MCI.[86]

Complementary tests and assessments

The diagnostic process may be complemented with neuropsychological testing. If the patient has experienced a cognitive decline by history with functional activities largely preserved, then the patient can be described as having MCI.[26]

During the diagnosis process and at follow-up, the patient should also be assessed for medical and psychological comorbidities.[23]

Physical examination

Neurologic examination findings can be helpful in the differential diagnosis of dementia. However, findings may be nonspecific, even in the presence of a brain tumor or other focal and structural lesions.

  • Cranial nerve examination: patients with vascular dementia can present with visual field deficits. Evidence of ataxia, nystagmus, and lateral gaze palsy may suggest underlying alcohol-related dementia. In advanced cases of dementia, pseudobulbar palsy (involuntary laughing or crying) may be present.

  • Motor examination: patients with vascular dementia can present with hemiparesis. Although isolated extrapyramidal signs occur in both Alzheimer disease and normal aging (e.g., masked face, resting tremor), rigidity, bradykinesia, and abnormal speech and posture (especially in combination) are much less common in healthy older people.[87]

  • Sensory examination: sensory findings (such as a peripheral neuropathy) may implicate an underlying nutritional deficiency, or metabolic or toxic condition.

  • Coordination and gait: some patients with vascular dementia have transient gait abnormalities. Gait abnormalities, impaired vibration or position sense, spasticity, and paresthesias may be found in patients with vitamin B12 deficiency. Patients with normal pressure hydrocephalus (NPH) can have pronounced gait disturbance.[70][71][72]

  • Reflexes: the findings on examination are usually normal in early Alzheimer disease, although primitive reflexes (glabellar, grasp, and snout) may be present.[88] Patients with vascular dementia may demonstrate asymmetric deep tendon reflexes, a unilateral extensor plantar response, or visual field deficits. Creutzfeldt-Jakob disease is suggested when generalized myoclonus (with a prominent startle response) and motor disorders are present.[30]

  • Hearing test: hearing loss from central auditory dysfunction (i.e., sentence identification in a background of competing speech) reflects abnormal cortical processing and is more common with even mild cases of dementia than presbycusis, a form of hearing loss common in healthy older people.[89]

  • Cardiovascular examination: in patients with vascular dementia there may be hypertension, dysrhythmias (e.g., atrial fibrillation), peripheral vascular disease (such as carotid bruits), valvular disease, or congestive heart failure.

Psychiatric evaluation

Mood, affect, thought process, and thought content should be evaluated because depression and other psychiatric disorders can impair cognitive function. Social withdrawal, paranoia, and anxiety are frequent and early signs of Alzheimer disease.[90]

Depression and delusions are common in patients with vascular dementia, and "emotional incontinence" such as extensive mood lability can be found in advanced stages.[91]

Personality changes, disinhibited behaviors, social withdrawal, and lack of insight are often found in the early stages of Pick disease.

Mood and psychotic symptoms are not uncommon in patients with Parkinson disease who are developing a dementing illness.[69]

When psychiatric and/or behavioral symptoms are suspected, use of standardized scales like behavioral pathology in Alzheimer disease rating scale (Behave-AD), the neuropsychiatric inventory (NPI), and the Cohen Mansfield agitation inventory (CMAI) can be used. Instruments developed specifically for the measurement of depressive symptoms and the apathy syndrome in the patient with dementia include the Cornell scale for depression in dementia, the EURO-D scale for depression, and the apathy inventory.

Assessment of patients with behavioral disturbances includes not only an objective evaluation of their cognitive and behavioral profile, but also of their global functional status.[92] The use of standardized neurobehavioral scales will assist in qualifying and quantifying these symptoms and behaviors based on the type of dementia, leading to optimized treatment plans.[93]

Neuropsychological testing

Neuropsychological testing is recommended when dementia is suspected clinically, but the results of the initial evaluation are equivocal or the diagnosis is unclear. It can also be useful in distinguishing depression from dementia and a diffuse process from a focal one. In some cases, neuropsychological testing may offer a detailed report to consolidate symptoms of the thought disorder seen in dementias and can point to a specific region of the brain affected by the process (e.g., the frontal lobe).

Testing can provide additional data when decisions about driving, occupation, safety, and competence must be made.[94]

Baseline studies are important in determining prognosis and in assessing response to drugs.

In many cases, these more exhaustive evaluations are unnecessary. When they do become necessary, normative data on commonly used neuropsychological tests have become available to assess performance in older patients (up to 100 years of age).[95]

Laboratory evaluation

Laboratory testing is performed to find partially reversible or reversible causes of dementia. In one published series, 5% of elderly outpatients with suspected dementia had underlying metabolic abnormalities (hypothyroidism - in 3%, hyperparathyroidism, hyponatremia, or hypoglycemia) that were thought to have produced or contributed to the cognitive impairment.[96] The following are initial tests in all patients:

  • Blood chemistry profiles (including glucose, sodium, potassium, chloride, bicarbonate, BUN, and creatinine)

  • CBC with differential

  • Thyroid stimulating hormone

  • Cobalamin level

  • Folate level

  • Erythrocyte sedimentation rate (abnormal is >25 mm/hour or age in years + 10 [if female] divided by 2)

  • C-reactive protein

  • Urinalysis

  • Urine microscopy and culture

  • Chest x-ray

  • Nontreponemal serology test (e.g., serum rapid plasma reagin [RPR] test or serum Venereal Disease Research Laboratory [VDRL] test)

The following tests should be considered:

  • Fasting blood glucose (if random blood glucose is abnormal or equivocal)

  • HIV testing in those considered at risk

  • Urine toxicology panel (for opiates, benzodiazepines, cannabinoids, and cocaine)

  • Collagen vascular profile (if there is evidence of systemic vascular involvement)

  • Urinalysis for heavy metals for patients who are considered at risk by history (i.e., suspicion of poisoning, social exposure to lead)

  • Cerebrospinal fluid Venereal Disease Research Laboratory (CSF-VDRL) followed by fluorescent treponemal antibody absorption test, if indicated, for suspected neurosyphilis.[97]

Developments in biomarkers continue to increase diagnostic certainty for dementias.[1][98]​​[99][100][101]

Neuroimaging

Despite the relative rarity of intracerebral conditions such as tumor, hematoma, or hydrocephalus, structural imaging studies should be performed because these lesions are easily detected and often treatable.[23][102]​​[103]​​​​ Neuroimaging can also be used to improve positive or negative predictive value in the diagnosis of more common causes of dementia.​[102]​​[104][105]

To assess progression and identify patients with progressive mild cognitive impairment (MCI), several noninvasive imaging methods are available; however, there is no consensus on the ideal imaging approach. Head computed tomography (CT) or head magnetic resonance imaging (MRI) are the main modalities.[102]​ MRI is recommended over CT for investigating vascular cognitive impairment and is more sensitive than CT for evaluating atrophy, vascular lesions, and lesions adjacent to bone.[23][106]​ ​​However, the clinical utility of these findings in the evaluation of most cases of dementia is unclear. 

Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a useful supplement to current surveillance techniques, with a predictive accuracy better than that of single-photon emission tomography or MRI.[102][107]​​ It is also used to aid in the diagnosis of frontotemporal dementia.[105][108][109]​​​ Brain amyloid PET/CT can increase diagnostic confidence for Alzheimer dementia, or lead to a change of suspected etiology of the cognitive impairment.[102]

Cerebrospinal fluid (CSF) analysis

Biochemical, immunologic, microbiologic, or cytologic analysis of the cerebrospinal fluid (CSF) can be considered in the following situations:

  • Dementing illnesses of acute or subacute onset (especially in patients with fever or nuchal rigidity)

  • Atypical or rapidly progressive initial manifestations

  • Dementia in persons <55 years of age

  • Suspected syphilis

  • Suspected infection or malignant lesion of the CNS[30]

  • Patients with evidence of hydrocephalus[110]

  • Creutzfeldt-Jakob disease[111]

  • Immunosuppression

  • Demyelinating disease

  • Vasculitis (e.g., in the presence of connective tissue disease).

Patients should be evaluated for raised intracranial pressure before performing a lumbar puncture.

Electroencephalogram (EEG)

Overall, EEG has limited utility in the initial evaluation of dementia. Generalized slowing of the background rhythm on EEG is a frequent finding in Alzheimer dementia, Lewy body dementia, and encephalopathy EEG may be helpful in distinguishing these patients from those with depression.

The EEG can be used in cases of dementia in which a high clinical suspicion exists for an atypical disorder (e.g., Creutzfeldt-Jakob disease) where a characteristic EEG finding of periodic sharp wave complexes can aid in the diagnosis.

Specialty consultations

Timely referral to a dementia or neurodegenerative disease specialist facilitates classification of dementia and pharmacological treatment if appropriate. Available data indicate that primary care physicians correctly identify those patients with mild cognitive impairment (MCI) and mild dementia less than half of the time.[112] 

Neurology specialty evaluation may also be considered in patients who have cognitive impairment of recent onset (<12 months), when atypical manifestations (e.g., strokes, seizures, or focal neurologic findings) are present, when memory loss or dementia is suspected clinically but cognitive testing shows normal findings, or when there is an unclear diagnosis.

The use of guidelines such as the European Federation of Neurological Societies (EFNS) guideline for the diagnosis of Alzheimer disease improves the diagnostic accuracy.[63] Practical guidelines can help primary care physicians, who are often the first clinicians to evaluate individuals with cognitive issues, to correctly diagnose individuals with dementia.[22]

Genetic testing

Genetic testing is appropriate in patients with cognitive dysfunction who have a documented family history of dementia and who request such testing.[113]

Mutations in the amyloid precursor protein (APP) gene and the presenilin genes 1 and 2 (PSEN1 and PSEN2) explain 50% of the familial form of early-onset Alzheimer disease.[63] ​The apolipoprotein E epsilon 4 (ApoE ε4) allele is the strongest genetic risk factor for late-onset Alzheimer disease, but it is neither necessary nor sufficient for development of the condition.[114][115][116]

Genetic testing for the three common genetic abnormalities of behavioral variant frontotemporal dementia (bvFTD) — GRN, MAPT and C9orf72 — is indicated if at least one first-degree relative is affected. A positive family history should be considered to extend beyond FTD and young-onset dementia to include Parkinson disease or related disorders, ALS and unexplained late-onset psychiatric disorders.[108][109]​ Screening for C9orf72 mutations should take place for all patients with suspected FTD with prominent psychiatric symptoms or family history of late-onset primary psychiatric disorder (even if full diagnostic criteria are not met).[108]

Confirmation of diagnosis

The diagnosis of dementia can be confirmed by postmortem neuropathologic assessment of the brain. The National Institute on Aging-Alzheimer’s Association has published updated guidelines for the neuropathologic assessment of Alzheimer disease.[117]

In living patients, developments in biomarkers continue to increase diagnostic certainty.[1][98][99][100][101]

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