Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than half of cases with cognitive impairment. With numbers of patients expected to rise sharply over the following years in parallel with the ageing of population, there is intense clinical interest in discovering modifiable risk factors that may contribute to the increasing prevalence of AD. Accumulating data from in vitro and epidemiological studies have highlighted the vascular component of AD and raised hope that treatment of vascular risk factors could eventually lead to primary prevention of AD. Among all the possible pathologic processes that have been tested for an association with AD, diabetes, hypertension and dyslipidemia are the most prominent. Here, we will briefly review the data highlighting a potential correlation of these diseases with AD. Then, we will present observational studies and clinical trials that assessed the impact of their respective approved medical therapies on AD incidence. We conclude by providing clinical information for the physician on potentially effective and non-effective medical treatments. Further research is ongoing and time will show whether AD will cease to be considered a pure, non-preventable neurodegenerative process or whether vascular risk factor management may also result in primary AD prevention.

The classical cerebrospinal fluid biomarkers of Alzheimer's Disease (namely total tau, phospho-tau and amyloid beta peptide) have received much attention, since they can detect the biochemical fingerprint of Alzheimer's disease and serve as a diagnostic aid for correct diagnosis of cognitive disorders during life. In this case series, we present 6 examples of patients with cognitive impairment of various types and severities and how biomarker data were helpful in every day diagnostic approach, combined with clinical, neuropsychological and imaging data and based on the most recent guidelines and recommendations.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), is the most common cause of inherited cerebral small vessel disease, inherited stroke and inherited vascular dementia. It is not infrequent for CADASIL to be mistaken and mistreated for multiple sclerosis (MS). A much less frequent but existing scenario is the co-occurrence of CADASIL and MS (or MS-like inflammatory condition). Such patients may present with spinal cord lesions, brain or spinal cord enhancing lesions, positive oligoclonal bands and high IgG index in the cerebrospinal fluid and good response to corticosteroids or immunomodulating treatments. CADASIL through various mechanisms may trigger or modulate autoimmune reactions, and either be complicated by an inflammatory component or cause an MS-like disorder.

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Hereditary forms of subcortical small vessel disease (SSVD) leading to vascular cognitive impairment (VCI) comprise a heterogeneous group of rare genetic disorders, suitable for the study of the mechanisms and relationship between SSVD and VCI. Since these disorders are rare, better knowledge of their clinical, genetic, imaging and biochemical characteristics may be achievable only through registries which additional may help in better recruitment of patients for studies. A great amount of our current knowledge on these disorders has been gained through registries and data bases. International registries may further help in expanding our experience in epidemiological or even preventive and therapeutic aspects of hereditary SSVD.