Start available symptomatic medications at earliest possible stage to reduce burden of symptoms
Identify patients who would best benefit from disease modifying medications as they become available
Patients can participate in clinical trials to test new therapies
Allows clinicians to anticipate problems the patients may have adhering to recommended therapy
Assisting the patient’s caregiver and family in planning for the future-advanced directives, durable power of attorney, long-term care plans
Permits input from patient at a stage where they are capable of contributing to their medical, financial, and social decision-making process
Early referral to community resources, social services, and support groups
Non-pharmacological interventions including those directed at caregivers to reduce stress, alleviate mood, delay nursing home placement and improve well-being
Currently, many brief screening measures utilized and described in this volume (e.g. the Mini Mental State Exam or MMSE; see Chap. 3) [7] rely on patient performance, and when used in isolation may have limited ability to detect cognitive impairment in the community [8–10]. The challenge with brief instruments is whether very mild impairments can be discriminated from normal aging in a time-efficient manner. A number of brief performance-based dementia screening measures are already in use, but may be: (1) unable to detect or quantify change from previous levels of function; (2) insensitive to subtle changes in high functioning individuals (i.e. ceiling effects) who may score well within the normal range throughout the early stages of dementia; (3) unable to discern decline in individuals with poorer lifelong abilities; and (4) culturally insensitive, thereby underestimating the abilities of underrepresented minority groups.
Informant based instruments rely on an observant collateral source to assess whether there have been changes in cognition and if said changes interfere with function. A particular strength when compared to other cognitive screening tests is informant assessments are relatively unaffected by education and premorbid ability or by proficiency in the culture’s dominant language. Because each person serves as their own control, there is little bias due to age, education, gender or race [3, 5, 10]. The disadvantages of informant assessments are the reliability of the informant and the quality of the relationship between the informant and the patient. Informant-based assessments are less likely to have floor or ceiling effects [10–13]. However, reliable informants may not always be available, may minimize symptoms, have cognitive impairment of their own, or may have secondary motivations. A solution to this disadvantage is to administer a performance based test in addition to the informant based assessment to improve screening accuracy and sensitivity [14]. The Alzheimer Association [15] and the National Guideline Clearinghouse [16] recommends the combined use of an informant interview with a performance measurement to detect dementia most efficiently.
A gold standard in informant assessment is the Clinical Dementia Rating (CDR). It is used to determine the presence or absence of dementia and, if present, to stage its severity [17]. The CDR evaluates cognitive function in each of six categories (memory, orientation, judgment and problem solving, performance in community affairs, home and hobbies, and personal care) without reference to psychomotor performance or results of previous evaluations. A CDR score of 0 indicates no dementia; CDR score of 0.5 indicates very mild dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia. The CDR is sensitive to clinical progression and is highly predictive (93 %) of autopsy-confirmed Alzheimer’s disease [18, 19]. The CDR is sensitive to early symptomatic Alzheimer’s disease and provides sufficient information to stage dementia severity and monitor dementia progression. The length of time to administer the test is its main limitation (45–60 min) and it is unlikely to be suitable for general clinical practice.
Relatively few brief informant tools have been validated in community and/or primary care settings. In particular a brief informant test that has been validated against a gold standard informant assessment, neuropsychological testing, and biomarkers would be of particular value. One such test is the AD8 [10].
14.2 The AD8
The AD8 is a brief screening interview comprised of eight Yes/No questions asked of an informant to rate change, and takes approximately 2–3 min for the informant to complete (Table 14.2). In the absence of an informant, the AD8 can be directly administered to the patient as a self-rating tool [10–13] with similar large effect sizes (Cohen d for informant = 1.66; for patient = 0.98). The AD8 reliably differentiates between individuals with and without dementia by querying memory, orientation, judgment, and function [10].
Table 14.2
The AD8
Remember, “Yes, a change” indicates that there has been a change in the last several years caused by cognitive (thinking and memory) problems | Yes, a change | No, no change | N/A, don’t know |
1. Problems with judgment (e.g. problems making decisions, bad financial decisions, problems with thinking) | |||
2. Less interest in hobbies/activities | |||
3. Repeats the same things over and over (questions, stories, or statements) | |||
4. Trouble learning how to use a tool, appliance, or gadget (e.g. microwave, remote control) | |||
5. Forgets correct month or year | |||
6. Trouble handling complicated financial affairs (e.g. balancing checkbook, income taxes, paying bills) | |||
7. Trouble remembering appointments | |||
8. Daily problems with thinking and/or memory | |||
Total AD8 score |
Originally developed in a research sample [10] and validated in a clinic sample [11], the AD8 offers a number of properties that make it particularly useful as a simple, brief screening tool. The AD8 has a sensitivity of 84 %, and specificity of 80 % with excellent ability to discriminate between non-demented older adults and those with mild dementia (92 %) regardless of the cause of impairment [11]. Use of the AD8 in conjunction with a brief assessment of the participant, such as a word list recall, could improve detection of dementia in the primary care setting to 97 % for dementia and 91 % for MCI [13].
The AD8 is highly correlated with the CDR and neuropsychological testing as well as amyloid PET imaging and cerebrospinal fluid biomarkers of AD [20]. Participants with positive AD8 scores (graded as a score of 2 or greater) exhibited AD biomarker phenotypes characterized by significantly lower levels of CSF Aβ42, higher levels of CSF tau and phosphorylated tau, smaller temporal lobe and hippocampal volumes on MRI and increased Aβ binding on PET scans (Table 14.3; Fig. 14.1). Strength of association was greater for the AD8 with biomarkers than for brief performance tests such as the MMSE or Short Blessed Test. Perhaps even more interesting were the changes in biomarker profiles in false-positive individuals (rated as non-demented on gold standard evaluations but AD8 scores ≥2). In a post-hoc analysis of 156 individuals [3], 25 individuals rated as impaired on the AD8 had higher CDR sum of box scores, were more likely by the informant to rate problems in memory and problem solving, and tended to have higher amyloid binding on PET scans (Table 14.4). This would suggest that a proportion of false positive individuals on AD8 screening may in fact represent individuals with preclinical AD.
Table 14.3
Relationship of AD8 to Alzheimer pathology biomarkers
Variable | AD8 <2 | AD8 ≥2 | p-value |
|---|---|---|---|
Demographics | |||
Age, y | 75.3 (7.2) | 75.5 (7.5) | ns |
Education, y | 15.3 (3.2) | 14.8 (3.2) | ns |
ApoE, % at least 1 e4 allele | 30.1 | 48.7 | .003 |
Dementia ratings | |||
CDR-SB, range 0–18 | .06 (.19) | 2.8 (2.5) | <.001 |
AD8, range 0–8 | 0.3 (0.5) | 5.0 (2.1) | <.001 |
Biomarker studies | |||
Amyloid PET, MCBP units | .12 (.23) | .45 (.42) | <.001 |
CSF Aβ42, pg/ml | 590.7 (266.2) | 435.6 (209.6) | <.001 |
CSF tau, pg/ml | 303.6 (171.2) | 500.5 (261.3) | <.001 |
CSF p-tau181, pg/ml | 52.2 (23.9) | 76.7 (39.9) | <.001 |
CSF tau/Aβ42 ratio | .72 (.75) | 1.4 (1.1) | <.001 |
CSF p-tau181/Aβ42 ratio | .12 (.11) | .22 (.16) | <.001 |
Fig. 14.1
Relationship of AD8 to MRI volumes. Panel A: Comparison of temporal lobe volume between individuals with AD8 scores 0 or 1 (nondemented) and individuals with AD8 scores 2 or greater (demented). Temporal lobe volumes are significantly smaller in individuals who have positive AD8 scores (p = 0.009). Panel B: Correlation between AD8 and CDR scores with total gray and white matter volumes and 8 cortical regions. Higher AD8 scores and CDR stages are strongly correlated with smaller volumes in the temporal lobe, hippocampus, and parahippocampus
Table 14.4
Characteristics and biomarkers of non-demented individuals stratified by AD8 scores
Variable | AD8 <2 | AD8 ≥2 | p-value |
|---|---|---|---|
Clinical characteristics | |||
Age, y | 75.2 (7.1) | 76.5 (8.4) | 0.41 |
Education, y | 15.4 (3.2) | 15.9 (2.7) | 0.47 |
ApoE status, % at least 1 e4 allele | 25.8 | 34.4 | 0.08 |
Dementia ratings | |||
CDR-SB | 0.04 (0.13) | 0.12 (0.22) | 0.01 |
MMSE | 28.6 (1.5) | 29.2 (1.1) | 0.07 |
AD8 questions endorsed “Yes”, % | |||
Problems with judgment | 12.9 | 72.0 | <0.001 |
Reduced interest | 0 | 4.0 | 0.02 |
Repeats | 8.3 | 40.0 | <0.001 |
Trouble with appliances | 1.5 | 40.0 | <0.001 |
Forgets month/year | 0.8 | 0 | 0.66 |
Trouble with finances | 0.8 | 16.0 | 0.002 |
Forgets appointment | 2.3 | 28.0 | <0.001 |
Daily problems with memory | 20.0 | 66.7 | 0.008 |
Biomarkers | |||
Amyloid PET, MCBP units | 0.12 (0.23) | 0.26 (0.39) | 0.06 |
CSF Aβ42, pg/ml | 596.7 (267.9) | 591.9 (249.9) | 0.95 |
CSF tau, pg/ml | 300.3 (171.5) | 316.7 (155.0) | 0.76 |
CSF p-tau181, pg/ml | 51.9 (24.0) | 56.9 (22.6) | 0.49 |
In a comparison of the AD8 to another commonly used informant measure, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE; see Chap. 13) [21–23], both were able to detect the presence of cognitive impairment in community settings and were highly correlated with brief assessments of cognitive ability (MMSE, Mini-Cog, Clock Drawing, and Animal naming) that are commonly used in community settings [23]. Both the AD8 and the IQCODE differentiated cognitively normal from individuals with dementia, however, the AD8 was better than the IQCODE in detecting MCI [24]. While the IQCODE covers two aspects of memory (acquisition of new information and retrieval of existing knowledge) and two aspects of intelligence (verbal and performance), the AD8 contains items that relate to memory, problem-solving abilities, orientation, and daily activities.
14.3 Studies of the AD8
14.3.1 In the Acute Care Setting
Both the AD8 and the IQCODE have been effectively used to detect prior dementia in hospitalized older patients with delirium [25]. Abnormalities on the AD8 on admission contributed to a two-fold risk for delirium during hospitalization [26] and when combined with a brief performance test maximized specificity and sensitivity. The AD8 has been used by hospital staff to increase detection of dementia in previously undiagnosed patients [27] and develop discharge planning.
14.3.2 Combining the AD8 with Performance-Based Instruments
In a study of primary healthcare centers in Singapore, the AD8 was combined with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network protocol to detect patients at-risk for cognitive impairment. This combined protocol had a sensitivity of 73 % and positive predictive value of 92 % [28] and was a reliable measure to detect cognitive dysfunction in primary healthcare settings [29]. In a pragmatic diagnostic test accuracy study, the AD8 showed excellent sensitivity but poor specificity when used alone in a general clinic population. Combining the AD8 with a performance based test improved specificity while sacrificing some sensitivity [14].
14.3.3 As a Patient-Based Assessment of Subjective Cognitive Impairment and Insight
When asked of potential patients, studies of the AD8 reveal two phenomena. The patient with insight is able to effectively rate the presence of cognitive symptoms but may not be able to rate severity of symptoms [12]. This was independently confirmed in a study of Asian older adults [30]. Furthermore, for patients with clearly demonstrable cognitive deficits the AD8 may help discern anosognosia (the denial or lack of awareness of deficit) that can contribute to problems with medication adherence and caregiver burden [31].
14.3.4 As a Predictor of Recovery of Function
The presence of physical frailty or cognitive impairment prior to injury may contribute significantly to the rehabilitation potential of an older adult. The AD8 can be used to help independently predict post injury functional status and mortality in geriatric trauma patients [32].
14.3.5 Use in Population Dementia Screening
The AD8 was used by the 10 Area Agency on Aging offices in Missouri to screen nearly 4000 older adults during routine home visits [33]. Prevalence of cognitive impairment was 28 % and this program was able to refer individuals for additional community services. In a walk-in screening program in Taiwan, 2171 individuals were screened over a 2-year period with the AD8 with a dementia prevalence of 14 % [34]. In an epidemiologic study of African American older adults, the AD8 had high sensitivity and specificity to discriminate older adults with and without cognitive impairment (area under curve 0.85, p < .001) [35].
14.3.6 Spanish
The AD8 was tested in a sample of 330 individuals with strong correlation to Global Deterioration Scores (r = 0.72, p < .001) [36] and when combined with a brief performance test demonstrated excellent discrimination (area under curve 0.96, p < 0.05). Similar studies have reported strong psychometric properties of the AD8 in Chile [37, 38], and Ecuador [39, 40].
Related posts:
The General Practitioner Assessment of Cognition (GPCOG)
The IQCODE: Using Informant Reports to Assess Cognitive Change in the Clinic and in Older Individuals Living in the Community
Six-Item Cognitive Impairment Test (6CIT)
Assessment of the Utility of Cognitive Screening Instruments
Montreal Cognitive Assessment (MoCA): Concept and Clinical Review
The Quick Mild Cognitive Impairment Screen (Qmci)
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