Progression in Cognitive ADLs in Parkinson's Disease

Mild cognitive impairment (PD-MCI) is one of the greatest risk factors for future Parkinson's disease dementia (PDD). A recent meta-analysis found that, on average, 31% of patients with PD-MCI converted to PDD within seven years; however, 24% of patients with PD-MCI reverted back to normal cognitive function. Consequently, the false positive rate for predicting PDD among patients with PD-MCI is high, and better predictive markers to define patients at high risk for PDD development are urgently needed. Therefore, a combination of different markers, including clinical, genetic, and other biomarker data, are proposed to increase ability to predict cognitive worsening and dementia. Based on data of the first follow-up of this cohort results indicated that presence of both mild cognitive instrumental activities of daily living (IADL) impairment and PD-MCI dramatically increases the risk for PDD (PubMed ID: 36240089). This study evaluates markers predicting cognitive and IADL long-term outcome in our sample. Additionally, focus of the study is the investigation whether ratings of patients or informants best predicted decline of cognitive impairment and/or everyday function. Clinical data along with other clinical marker and biomarker status will be investigated.

Patients assessments: Most scales (except for Kölner Apraxie Test) were also included in the first follow-up of the sample. Total duration of scales and questionnaires is 4 hours (total time of mandatory in house assessments: 115 min).

Demographic and lifestyle data: Age, gender, education, occupation, family history of neurodegenerative diseases, smoking/drinking behavior, height \& weight will be registered.

Activities of daily living assessment: The total and subscores of the Pfeffer Functional Activities Questionnaire (score range 0 to 30 higher values indicating more impairment) will be assessed. Additionally patients assessment includes the Parkinson's disease Activity of daily living scale (five level scale, higher values indicating more impairment).

Neuropsychological Assessment: History and self-awareness of cognitive deficits will be asked. Overall mean z-score (range -3.00 poor performance to +3.00 excellent performance) and cognitive domain score (mean z-score of tests assigned to one domain) will be quantitatively assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) battery, three subtests of the Wechsler Intelligence Test for Adults (WIE), and one subtest of the Leistungsprüfsystem für 50- bis 90-Jährige (LPS 50+). The MMSE included in the CERAD-Plus, as well as the Montreal Cognitive Assessment (MoCA) will serve as global cognitive screening scales.

* Executive functions: Lexical and Phonemic Fluency (CERAD-Plus), Trail Making Test Part B (CERAD-Plus)
* Attention/working memory: Digit-Symbol Test (WIE), Letter-Number Sequencing (WIE)
* Language: Boston Naming Test (CERAD-Plus), Similarities (WIE)
* Memory: Word List Learning, Recall, and Discriminability (CERAD-Plus), Praxis Recall (CERAD-Plus)
* Visuospatial abilities: Praxis (CERAD-Plus), Fragmented Words (LPS-50+)

The Dementia Apraxia Test developed to assess limb and buccofacial apraxia in neurocognitive disorder patients with Alzheimer's disease and frontotemporal dementia will be additionally applied. For validation purpose, the Kölner Apraxie Screening will be included as well.

Clinical motor assessment: The Movement Disorder Society Unified Parkinson's disease rating scale (score 0 to 132) including the Hoehn and Yahr stage (score 0-5) will be applied. The Freezing of Gait Questionnaire (FOG) will be applied. Higher scale values indicated more severe impairment.

Additional non-motor assesssment: A comprehensive non-motor assessment will be applied including the Beck Depression Inventory II (BDI-II, score 0-63), the Beck Anxiety Scale (score 0-63), the Non-motor symptom Questionnaire (NMSQ, 0 to 30) and the Parkinson's disease Non-Motor Symptom Scale, subscales 1-5 (PD-NMS-S). In those scales higher values indicated more severe impairment.

Optional assessments:

* Blood withdrawal - 15 min
* Lumbar puncture - 30 min
* Ambulatory accelerometry device - 7 days

Caregiver assessments: To validate the patients' self-impression, caregiver questionnaires and interview scales will be applied, needing caregivers to be available for at least 38 minutes. Caregiver assessments will only be performed if the respective patient has agreed to the interview. The Bayer Activities of Daily Living Scale (1 point to 10 points with higher values indicating more impairment) answered by the caregiver and the Informant Questionnaire on Cognitive Decline in the Elderly (IQ-CODE, 26 points to 130 points, higher scores indicating more impaired performance) will be analysed.

Eligibility Criteria:
Between March 30th, 2014 and December 31th, 2017, a large cohort of 268 people with Parkinson's disease were recruited within the frame of the" Amyloid-Beta in cerebrospinal fluid as a risk factor for cognitive dysfunction in Parkinson's Disease" (ABC-PD) study. First follow-up was conducted between July 2018 and September 2020, including 182 (67.9%) patients. Those people with Parkinson's disease will be invited to participate in the proposed second follow-up assessment. If people with Parkinson's disease are not able to attend a clinical visit in-house, possibility of assessments at patients' homes shall be offered.

If people with Parkinson's disease or legal guardians give their consent a caregiver with regular contact to the patients will be ask to give information about patients instrumental activities of daily living, motor and non-motor status.

Inclusion Criteria:

* Participant in the " Amyloid-Beta in cerebrospinal fluid as a risk factor for cognitive dysfunction in Parkinson's Disease" (ABC-PD) study
* Diagnosis of Parkinson's disease according to the United Kingdom Brain Bank criteria.
* Ability to communicate well with the investigator, to understand and comply with the requirements of the study.
* Provide written informed consent to participate in the study and understand the right to withdraw consent at any time without prejudice to future medical care.
* If people with Parkinson's disease are not able to give consent for study participation (confirmed by an independent physician), study consent of a legal guardian is required.

Exclusion Criteria:

* Any disability that may prevent the subject from completing the informed consent form or other study requirements.
* Other neurodegenerative disease which renders the subject unable to communicate well with the investigator or to understand and comply with the requirements of the study.
* Participation in any clinical investigation of a new investigational compound or therapy within 4 weeks prior to baseline visit, and any other limitation of participation based on local regulations.
* Alcohol, medication, or drug dependency or abuse (except for nicotine).
* History of brain disease other than Parkinson's disease, e.g., head trauma, stroke, encephalitis.