Language, speech and motor function in mild cognitive impairment due to AD and Alzheimer*s disease

Alzheimer's disease (AD) is the most common subtype of dementia. AD is
characterized by pathological changes and a gradual deterioration of cognitive
functions. Clinical AD starts when signs and symptoms of AD appear. Before
clinical AD onset, AD involves a long period with pathological changes and
gradual deterioration of cognitive functions, but without the over
manifestation of clinical signs and symptoms of AD. This period before the
clinical onset of AD is usually divided into (1) preclinical AD (pathological
changes without detectable clinical symptoms) and (2) mild cognitive impairment
(MCI) (characterized by mild memory loss and pathological changes). In case of
clearly identifiable biomarkers of AD during this MCI stage, the stage is
called 'MCI due to AD' . As soon as clinical AD starts, the course of the
disease is divided into the following three stages: mild AD, moderate AD and
severe AD.

It's important to diagnose AD as early as possible in the course of the disease
for timely treatment and care. However, an early and accurate clinical
diagnosis of AD is challenging due to the absence of sensitive observable
clinical markers of the disease. Therefore, it is necessary to identify better,
more sensitive and more accurate observable clinical markers to identify AD at
(very) early stages of the disease.

The combination of characteristics of motor, speech and language impairment is
promising in this regard; it could possibly be used in the early detection of
AD, as evidence exists that changes in both domains are present across all
stages of AD. Furthermore, a few studies have tentatively shown that the
classification of people with AD, MCI and without cognitive impairment can be
improved by combining characteristics of multiple observable domains, including
language, speech and motor skills. Additionally, there are also some
indications that linguistic and motor profiles can differ across several forms
of dementia.

Therefore, the combination of language, speech and motor functions would be a
potential candidate in the early AD detection process, as deterioration of
language and motor are seen in the early stages of the disease. However,
scientific evidence of the combination of motor and language as improvement of
the detection of AD is limited and scarce.

Primary objective:
To determine the characteristics of language, speech and motor functions in MCI
due to AD, mild AD and moderate AD

Secondary objective:
To explore the association between language, speech and motor functions in MCI
due to AD and mild AD and moderate AD

Observational explorative cross-sectional study.

This study is a group-based explorative study which cannot be conducted without
persons with MCI due to AD, AD and a control group without cognitive
impairment. Based on the outcomes of this study, hypotheses can be formulated
for further large-scale studies investigating the combination of language,
speech and motor abnormalities as possible stronger clinical markers of AD.
Sample size power calculations indicated a minimum sample of 52 participants
for each group (persons MCI due to AD, mild AD and moderate AD, without
cognitive impairment) (Power = 0.8, Alpha = 0.05).

There is no proven benefit for the participants in this study. However, this
study cannot be conducted without persons with MCI due to AD, AD and an elderly
control group. We intend to keep the burden on participants as low as possible
through, among other things, the selection of the tests and study design. All
tests incur a relatively low burden on participants and there is no risk
exceeding that of regular activities. The tests in this study are also used in
clinical practice.

The entire test protocol can be administered in one single session. In case of
community-dwelling persons, multiple locations will be offered to administer
the tests. In case of institutionalized persons which cannot be displaced the
entire test protocol will be administered at their healthcare organization of
residence.

Participants can always decide to take a break, to continue the test procedure
at another time or to withdraw from the study altogether without any
consequences. In case of incapacitated participants, verbal and non-verbal
signs of resistance will continuously be monitored. If there is resistance or
the verbal or non-verbal signs are interpreted as resistance, the participant
will be excluded from this study. The definition of resistance from
*Gedragscode verzet bij wils-onbekwame (psycho) geriatrische patiënten (1999)
will be used In this study,. *Er is [*] sprake van verzet, indien het gedrag
duidelijk afwijkt of zich excessiever manifesteert dan men van de betrokkene
gewoon is in van de normale dagelijkse routine afwijkende
situaties* (Nederlandse Vereniging van Verpleeghuisartsen et al., 1999, p.3 In
case a participant has a legal representative, this person will be present
during the whole test assessment or another formal or informal care provider in
consultation with the legal representative who knows the participant well will
be tasked with this monitoring of resistance behavior.