Vascular Phenotypes in a Geriatric Population

The rising prevalence of dementia is a growing concern. With aging of the
population,
the number of people diagnosed with dementia is expected to increase to more
than 130 million cases worldwide in 2050. Alzheimer*s disease is the most
common dementia subtype, followed by vascular dementia. However, the majority
of dementia patients seems to suffer from mixed pathologies in which
cerebrovascular pathology is at least coexistent. For instance, in all
neurodegenerative diagnoses that are not of vascular origin, up to 85% of the
patients appears to have vascular pathology.
Vascular health and brain health are closely linked. Therefore, it is
not surprising that cerebral small vessel disease (CSVD), including white
matter hyperintensities, cerebral microbleeds and lacunes, has been associated
with (cardio-)vascular risk factors, such as hypertension, smoking and
atherosclerosis.Population attributable risk calculations within the Rotterdam
Study revealed that at least 25% of all dementia cases could potentially be
prevented through optimal prevention of cardiovascular risk factors and
treatment of cardiovascular disease.
Underlying mechanisms for the connection between vascular morbidity and
brain health are not clear. It has been hypothesized that microvascular damage
due to endothelial dysfunction could cause cerebral ischemic lesions, leading
to cognitive decline. Another microvascular manifestation, orthostatic
hypotension, appeares to be more prevalent among patients with Mild Cognitive
Impairment (MCI) or dementia. Alternatively, macrovascular damage, such as
atherosclerosis, could lead to an increased variability in blood pressure and
consequently, to lower cerebral blood flow, which has also been associated with
cognitive decline.
The effect of macro- and microvascular morbidity on cognitive decline,
physical decline and adverse outcomes such as hospitalization and mortality in
patients with memory complaints is not precisely known. More insight in the
relation between vascular phenotypes and the aforementioned outcomes is crucial
since (cardio-)vascular risk factors are potentially modifiable and treatment
of clinical dementia is not expected to be available in the near future.

The objective of this study is to relate different vascular phenotypes, based
on macro- and microvascular measurements, to changes in cognitive and physical
functioning in a geriatric population.

We plan to study the objectives with a longitudinal cohort study with a
follow-up of two years. This study will take place within the geriatric memory
clinic of the internal medicine - geriatrics department of the Amsterdam UMC -
VUmc. The value of the cohort lies in the extensive phenotyping of participants
and relatively long duration of follow-up. Some procedures that contribute to
the study data are part of routine care, and are collected for research
purposes under a general, not WMO-compliant, protocol. Some procedures are
additional for the purpose of this study. Only the vascular measurements during
the baselinevisit (or twee weeks following the baseline visit) and the
assessment during the follow-up visits at 6, 12 and 24 months are additional
for the purpose of this study. All other procedures during the baseline visit
are part of routine care.

There is no direct benefit for participants in this study. Risk associated with
participation in this study, which includes vascular measurements that do not
penetrate the participants body, are considered low. At the same day of their
second baseline visit, vascular measurements will be performed. During these
measurements, it is possible that a carotid stenosis is suspected. In that
case, patients will be notified of this finding, discussed with a vascular
specialist and referred if needed. Patients will also be referred to a vacular
specialist if the EndoPAT measurement is abnormal. During the endoPAT
measurement, a blood pressure cuff is inflated to 200mmHg for several minutes,
this can cause discomfort but is not dangerous. Another load on the
participants are the extra visits to the hospital (at 6, 12 and 24 months) that
are not part of regular care.