Abstract
A 55-year-old priest who retired due to significant cognitive decline.
1.2 Clinical History
The patient came to the consultation accompanied by his wife who provided most of the history. She described her husband as a priest with persuasive and eloquent oratory, which was highly appreciated by their religious community. However, during the last 3 years, there was a clear impoverishment of the patient’s ability to preach. During the services, he also started losing the thread of his narratives and getting confused on quoting the bible. His ability of multitasking in the church was impaired. A year later, he clearly acquired difficulties in retaining information regarding conversations as well as a hard time in organizing his day and accomplishing all the commitments of his agenda. Soon after, he started to forget contents of conversations and lost the ability to deal with calculations, and consequently, his financial affairs. He became unable to write. His wife also remarked the patient’s inability to focus attention on his tasks. He also had a little insight regarding his present limitations.
Apart from a general reduction in motivation and social isolation, from the neuropsychiatric perspective, there was no history of disinhibition, reduced impulse control, substance-related disorders, stereotypical or ritualistic symptoms, hallucinations, or delusions. He was previously evaluated by a neurologist who diagnosed him with Alzheimer’s disease (AD) based on clinical history, MRI, positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG; Figure 1.1), and results of biomarkers from the cerebrospinal fluid (CSF). He was on 10 mg of donepezil every morning.
Figure 1.1 Structural MRI shows parietal (A) and hippocampal atrophy (F; Scheltens = 2–3) with no white matter hyperintensities in the FLAIR imaging (B, G; Fazekas = 0). FDG PET shows bilateral hypometabolism in the precuneous (H) and temporoparietal cortex (C; L ≫ R). Tau PET (D, I) shows deposition in limbic, temporal, and frontal cortices, sparing primary motor cortex (Braak stage 5). Amyloid PET (E, J) showed high load in the precuneous, posterior cingulate, inferior parietal, and frontal cortices.
1.3 General History
This patient completed grade 12 and worked as a pastor and missionary until 53 years old. He was married once and had two daughters. He and his immediate family lived in many places with precarious urban infrastructure and sanitation including the sub-Saharan Africa. He was exposed to many tropical diseases, many of them not diagnosed. His previous medical history was negative for cardiovascular diseases, high blood pressure, hyperlipidemia, stroke, or diabetes. There was no history of current sleep disorders and cardiovascular, respiratory, urinary, sensory, or motor complaints.
1.4 Family History
His family history was negative for early-onset familial AD (EOFAD) but positive for late-onset familial AD (LOFAD; grandmother) and amyotrophic lateral sclerosis (ALS; father).
1.5 Examination
The physical examination was unremarkable. During the mental status exam, he was cooperative, attentive, and responsive and partially oriented in time and space. The immediate recall was normal. He was not able to correctly tell the months in reverse order. He made few mistakes on the serial 7. The design copy and clock drawing were abnormal. Reading and repetition were normal. He was capable of writing a simple sentence, but his writing skills were impaired. The single word and the sentence comprehension were normal. The content of language was impoverished. Verbal and semantic fluency was reduced. Anterograde memory evoked by a delayed recall showed deficits that were not corrected by cueing. The capacity for abstraction was abnormal. Montreal Cognitive Assessment (MoCA) was 12/30 (visuospatial: –4, serial 7: –3, fluency: –1, abstraction: –2, delay recall: –5, orientation: –3) and the Mini-Mental State Examination (MMSE) was 17/30 (orientation: –3, serial 7: –5, delay recall: –3, design copy: –1). The patient was not capable of executing motor sequences. No significant perseveration, omission, or commissions were observed. The rest of the neurological examination was normal.
1.6 Diagnostic Workup
This patient had normal hematology, biochemistry, and autoimmune profile. He had an EEG without features of Creutzfeldt–Jakob disease. An MRI ruled out brain infarcts or white matter hyperintensities (Fazekas = 0) with a mild progression of hippocampal atrophy (Scheltens = 2–3). MRI diffusion imaging was normal. The FDG PET scan showed reduction on the FDG uptake in the precuneus, temporoparietal cortex, sparing the posterior cingulate. The CSF analysis showed Aβ1–42 of 397 pg/mL, a total tau (t-tau) of 488 pg/mL, a hyperphosphorylated tau (p-tau) of 61 pg/mL, and an ATI index of 0.52. The patient engaged in a research protocol and also had a positive amyloid PET and tau PET showing high uptake in the temporal lobe (mesial, basal, and neocortical), precuneous, inferior parietal cortex, orbitofrontal cortex, and amygdala (Braak stage 5; see Figure 1.1). He had a genetic assessment that was negative for MAP, C09orf72, progranuline, PS1, PS2, and APP mutations. He was an APOE 2/3 carrier.
1.7 Diagnosis
The diagnostic in this case is sporadic young-onset AD with evidence of the AD pathophysiological processes.
1.8 Discussion
The objective of this case report is to highlight the use of appropriated criteria for AD biomarkers in clinical practice. In the present case, our patient had the clinical history of a dementing disease characterized by an insidious onset, a clear-cut history of worsening of cognition and cognitive presentation encompassing language, memory, and executive deficits in the absence of cardinal features or other neurodegenerative conditions. The term “young-onset dementia” designates symptom onset before 65 years of age. The cutoff of 65 years is arbitrary and reflects aspects related to retirement age rather than any biological criteria.
As the prevalence of non-AD pathologies is higher in young-onset dementia, the knowledge of AD pathophysiology might affect the clinical management, in terms of therapeutics with cholinesterase inhibitors. Biomarkers are useful for providing to the caregiver and family members information regarding disease prognosis. In case of a positive family history, the presence of AD pathophysiology could guide genetic investigation.
The same logic is applicable to atypical dementia cases, which are clinically characterized by the predominance of behavioral, visuospatial, or language symptoms instead of the typical amnestic presentation of AD. As in young-onset cases, there is a higher prevalence of other pathological substrates rather than AD among patients with atypical dementias.
Although the knowledge of disease processes underlying atypical cases has modest but significant clinical applications, this scenario might change dramatically with the introduction of preventive pharmacological therapies since the identification of the specific neuropathological processes is a sine qua non condition for disease-modifying therapies. Despite significant progresses of biomarker research, there is a limited number of clinically useful biomarkers, which are summarized in Table 1.1. The most acceptable indications for biomarkers in dementia are summarized in Table 1.2.
Table 1.1 Biomarkers available in clinical practice
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