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  • CUR11: How are Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) currently diagnosed according to published guidelines and in practice?
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How are Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) currently diagnosed according to published guidelines and in practice?

Authors: Antonio Migliore, Tapani Keranen, Sinikka Sihvo

Internal reviewers: Kristian Lampe

MCI was introduced as a clinical entity more than 20 years ago, and during this time, multiple definitions for the syndrome have been proposed {63}. MCI is defined as a syndrome with cognitive decline greater than expected for an individual’s age and education level but in the absence of significant effect on instrumental activities of daily living (ADL) {31}. The subjects with MCI have thus subjective cognitive complaints which can be objectively verified but no dementia. Subjects with MCI have most commonly isolated memory impairment (so called amnestic MCI) but also non-amnestic MCI (impairment in executive, language or visuospatial functions) may occur {63}. The impairment can be restricted to one cognitive domain or to multiple domains {63}. In considering this clinical and cognitive syndrome, it is important to emphasize that sharp demarcations between normal cognition and MCI and between MCI and dementia are difficult, and clinical judgment must be used to make these distinctions {2}.

Current definition and diagnostic criteria for MCI are present in {CUR-11 Table 2}. There are no specific operational criteria for the diagnosis of MCI that are applied in the clinical daily routine {63}. In the clinical diagnosis of MCI the first step is history taking followed by physical examination including cognitive assessment {32} {38} {85}. Information from spouses, other relatives and caregivers are important in assessing possible behavioral symptoms and ADL functions. For the demonstration of cognitive impairment, measures such as the Mini Mental State Examination (MMSE) score or Montreal Cognitive Assessment (MoCA) test can be used {13}. However, the evidence of the sensitivity of MMSE in the identification of MCI is not good and the value of MMSE in the diagnosis of MCI is very limited {53}. The clinician should also determine whether the impairment involves only one cognitive domain such as memory or are other cognitive domains impaired {63}. Thereafter, the etiology of MCI should be evaluated with neuroimaging and possibly by biomarkers {64}.

The key element in the diagnosis of AD is clinical history which needs to be supplemented with information impairment in ADL functions {38}.  Diagnosis of AD requires an assessment of cognitive function in all patients {38}. Quantitative neuropsychological testing should be performed in subjects with questionable or very early dementia {38}. The proposed diagnostic criteria for probable and possible AD are presented in {CUR-11 Table 3} {51}. AD can be definitely diagnosed only post mortem {5}. Brain imaging studies are an essential part of diagnostic setup of bot MCI and AD and magnetic resonance imaging (MRI) is preferred because it is superior to computed tomography (CT) in demonstration of cerebral atrophy {28} {30} {38}. Hippocampal atrophy, as demonstrated by coronal T1-weighted MRI images is the best established and validated imaging marker of AD {28}. Functional neuroimaging, i.e. positron emission tomography (PET) with [18]-fluorodeoxyglucose (FDG) or [11C]PIB may increase the accuracy of separating subjects with MCI from healthy individuals {14} {28} {38}. Furthermore, MRI and PET may help to predict which cases of MCI will convert to AD {14} {28} {38}. A meta-analysis of MRI studies, using voxel-based morphomery in MCI patients, found that the left medial temporal lobe (especially hippocampus and parahippocampal gyrus) is the most affected region in MCI subjects who will convert to AD {27}. In addition to neuroimaging, the value of chemical biomarkers in the diagnosis of AD has been investigated. Low cerebrospinal fluid (CSF) concentration of amyloid-b (Ab1 – 42), in combination with high total CSF tau and phosphorylated tau, can discriminate AD patients from healthy subjects with reasonable sensitivity  and specificity {7} {26} {54}.  Due to issues such as variation in the results for different laboratories and cut off values, more validation work has to be done before the measurements can be considered mandatory in the diagnostics of dementia {5} {7} {27}. Subjects with cognitive problems usually see first their general practitioner (GP). Studies have shown that GPs correctly identify less than 50% of the individuals with MCI and they also have difficulties in identifying mild dementia {55}.

 

CUR-11 Table 2. Core clinical criteria for the diagnosis of MCI. Adapted from {2}.

MCI - Criteria for the clinical and cognitive syndrome

Concern regarding a change in cognition.

There should be evidence of concern about a change in cognition, in comparison with the person’s previous level. This concern can be obtained from the patient, from an informant who knows the patient well, or from a skilled clinician observing the patient.

Impairment in one or more cognitive domains

There should be evidence of lower performance in one or more cognitive domains that is greater than would be expected for the patient’s age and educational background. If repeated assessments are available, then a decline in performance should be evident over time. This change can occur in a variety of cognitive domains, including memory, executive function, attention, language, and visuospatial skills. An impairment in episodic meory (i.e., the ability to learn and retain new information) is seen most commonly in MCI patients.

Preservation of independence in functional abilities

Persons with MCI commonly have mild problems performing complex functional tasks which they used to perform previously, such as paying bills, preparing a meal, or shopping. They may take more time, be less efficient, and make more errors at performing such activities than in the past. Nevertheless, they generally maintain their independence of function in daily life, with minimal aids or assistance.

Not demented

The cognitive changes should be sufficiently mild that there is no evidence of a significant impairment in social or occupational functioning.

 

 

CUR-11 Table 3. Diagnostic criteria for probable and possible Alzheimer’s disease dementia. Adapted from {51}.

Probable AD dementia

Core clinical criteria:

Probable AD dementia is diagnosed when the patient meets criteria for dementia, and in addition, has the following characteristics:

A. Insidious onset. Symptoms have a gradual onset over months to years, not sudden over hours or days;

B. Clear-cut history of worsening of cognition by report or observation; and

C. The initial and most prominent cognitive deficits are evident on history and examination in one of the following categories.

a. Amnestic presentation:

• It is the most common syndromic presentation of AD dementia.  The deficits should include impairment in learning and recall of recently learned information. There should also be evidence of cognitive dysfunction in at least one other cognitive domain.

b. Non-amnestic presentations: 

• Language presentation: The most prominent deficits are in word-finding, but deficits in other cognitive domains should be present.

• Visuospatial presentation: The most prominent deficits are in spatial cognition, including object agnosia, impaired face recognition, simultanagnosia, and alexia. Deficits in other cognitive domains should be present. 

• Executive dysfunction: The most prominent deficits are impaired reasoning, judgment, and problem solving. Deficits in other cognitive domains should be present.

D. The diagnosis of probable AD dementia should not be applied when there is evidence of (a) substantial concomitant cerebrovascular disease, defined by a history of a stroke temporally related to the onset or worsening of cognitive impairment; or the presence of multiple or extensive infarcts or severe white matter hyperintensity burden; or (b) core features of Dementia with Lewy bodies other than dementia itself; or (c) prominent features of behavioral variant frontotemporal dementia; or (d) prominent features of semantic variant primary progressive aphasia or nonfluent/agrammatic variant primary progressive aphasia; or (e) evidence for another concurrent, active neurological disease, or a non-neurological medical comorbidity or use of medication that could have a substantial effect on cognition.

Possible AD dementia

Core clinical criteria:

A diagnosis of possible AD dementia should be made.

Atypical course:

Atypical course meets the core clinical criteria in terms of the nature of the cognitive deficits for AD dementia, but either has a sudden onset of cognitive impairment or demonstrates insufficient historical detail or objective cognitive documentation of progressive decline.

Etiologically mixed presentation:

Etiologically mixed presentation meets all core clinical criteria for AD dementia but has evidence of (a) concomitant cerebrovascular disease, defined by a history of stroke temporally related to the onset or worsening of cognitive impairment; or the presence of multiple or extensive infarcts or severe white matter hyperintensity burden; or (b) features of Dementia with Lewy bodies other than the dementia itself; or (c) evidence for another neurological disease or a non-neurological medical comorbidity or medication use that could have a substantial effect on cognition.

 

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Migliore A et al. Result Card CUR11 In: Migliore A et al. Health Problem and Current Use of the Technology In: Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 30 October 2020]. Available from: http://corehta.info/ViewCover.aspx?id=267

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