DIAGNOSIS

The gradual and insidious course of dementia due to Alzheimer’s disease and the heterogeneity of its manifestations make the diagnosis complex and elusive, particularly in the early stages. Cognitive changes need to be assessed and interpreted in the context of age-related deterioration in memory and other cognitive abilities.1 A diagnosis of Alzheimer’s Disease (AD) is most commonly made by a primary care physician.2

Physicians have an opportunity to perform a health risk assessment of their patients during the annual wellness visit.3 There are several tools that can be used to detect cognitive impairment quickly and reliably in a general practice setting.3,4  Many patients and caregivers come to these wellness visits with concerns about memory loss and dementia. Informing a patient about an AD diagnosis is crucial to counteracting the uncertainty and fears and also to beginning the treatment plan that will maintain a patient’s health and autonomy for as long as possible.3 Patients who are diagnosed with AD early may receive maximum benefits from current AD treatments and may be eligible for more clinical trials over the course of their disease.2,3

Dementia Diagnostic Workup

Cognitive screenings can be performed for anyone reporting memory loss or other warning signs of dementia during a mental status examination.3 Risk factors to consider during screening include age and gender, genetic predisposition, lifestyle effects (eg, diet and exercise), and comorbid conditions (eg, obesity, diabetes, cardiovascular disease, and depression).2 A baseline screen may also be helpful in patients who have not developed any signs or symptoms.3

Any diagnostic workup, including the one conducted during the annual wellness visit, should start with a detailed medical, psychiatric, and family history.3 Patients with potential signs of AD should receive a dementia workup to establish a diagnosis and differentiate AD from conditions that can mimic it, including medications (eg, sleeping pills) or stressors and social situations that could impair cognition.2

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) distinguishes between the diagnosis of mild versus major neurocognitive disorder, with the latter previously called dementia and characterized by decline in one or more of the cognitive domains: complex attention, executive function, learning and memory, perceptual-motor, and social cognition (see table).5

Definitions of Neurocognitive Disorders: DSM-55
Mild Neurocognitive Disorder (eg, mild cognitive impairment, prodromal AD)
Major Neurocognitive Disorder (dementia, eg, due to AD)
  • Mild cognitive decline, preferably diagnosed by neurocognitive testing or, in its absence, other quantified clinical testing
  • Does not interfere with independence
  • Not due to delirium
  • Not attributed to another mental disorder (eg, major depression, schizophrenia)
  • Major cognitive decline, preferably diagnosed by neurocognitive testing or, in its absence, other quantified clinical testing
  • Interferes with independence
  • Not due to delirium
  • Not attributed to another mental disorder (eg, major depression, schizophrenia)
  • The Alzheimer’s Association has prepared a Cognitive Assessment Toolkit for an annual wellness visit that assembles three validated patient assessment tools: the General Practitioner Assessment of Cognition (GPCOG), the Memory Impairment Screen (MIS), and the Mini-Cog™. These screening tests can be conducted in the clinic by any healthcare provider in 5 minutes or less.4 The tools provided test short-term recall, memory of recent experiences, and spatial function with a standard clock-drawing exercise. Caregivers may also be interviewed about changes in the patient’s memory and life-management skills. No individual tool for detecting cognitive impairment is considered a “gold standard”; false negatives commonly occur.3 Some providers perform assessments with two independent tools to confirm the initial result.3,4 Patients with overt signs and symptoms of AD or patients with questionable results during cognitive assessment should undergo a full dementia evaluation.4

    diagnostics-1

    Adapted from Cordell CB et al. Alzheimers Dement. 2013:9:141-150.

    Brain Imaging and Biomarkers in AD Diagnosis

    Brain imaging has become a useful, supplemental approach to confirm an AD diagnosis and to monitor disease progression.3 Magnetic resonance imaging (MRI) or computed tomography (CT) can detect brain atrophy. These imaging protocols are most frequently used to characterize disease progression in patients who recently developed AD and are experiencing rapid progression.3 Biomarkers may also be used to support a clinical diagnosis of AD.3

    Diagnostic Stages of AD

    In 2011, the National Institute on Aging-Alzheimer’s Association diagnostic guidelines for Alzheimer’s disease established three diagnostic stages of AD:6–9

    • Preclinical AD: Patients have measurable changes in biomarkers indicating disease development but have not developed overt symptoms of memory loss or cognitive impairment.
    • Mild cognitive impairment (MCI) due to AD: Patients have mild but measurable deficits in thinking abilities, but everyday activities are not affected.
    • Dementia due to AD: Patients have noticeable symptoms of the disease that affect memory, thinking, and behavior and that impact everyday activities.

    Patients should receive regular assessments of cognitive function to determine whether the disease is progressing.

    References

    1. Schaie KW, Willis SL, Caskie GI. The Seattle Longitudinal Study: relationship between personality and cognition. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2004;11:304-324.
    2. 2. Alzheimer’s Association. Alzheimer’s Association Report: 2017 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2017;13:325-373. Full report available at www.alz.org/documents_custom/2017-facts-and-figures.pdf
    3. Cordell CB, Borson S, Boustani M, et al. Alzheimer’s Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimers Dement. 2013;9:141-150.
    4. Alzheimer’s Association. Cognitive Assessment Toolkit. Report available at www.alz.org/documents_custom/141209-CognitiveAssessmentToo-kit-final.pdf
    5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association; 2013.
    6. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263-269.
    7. Jack CR Jr., Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:257-262.
    8. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s Disease. Alzheimers Dement. 2011;7:280-292.
    9. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270-279.

    Epidemiology

    Challenges

    Diagnosis

    Biomarkers

    Treatments

    Additional Reading