End-point diagnoses and prognostic determinants for neurodegeneration

Table 2 demonstrates the entire cohort classified upon the end-point primary diagnoses accounting for the symptoms bringing the patients to NPH clinic. NPH was confirmed in 113 patients (40 %), including 99 iNPH and 14 sNPH cases. Dementia-related

neurodegenerative diseases were common: AD (49 patients, 17 %) was the most common diagnosis, while there were also few cases of VAD, AD+VAD and FTLD. 5 patients (2 %) had firmly diagnosed PD. In addition to the 6 patients (2 %) with DLB, other Atypical Parkinsonian Syndromes were almost absent, as there was only one confirmed case of PSP and no one having MSA or CBD. Including this PSP patient, approximately one out of ten patients (27, 10 %) had a wide range of other neurologic diseases, like MCI, dementia NAS, alcohol dementia, possible neurodegenerative

disease, psychiatric diagnosis, epilepsy, polyneuropathy or vertigo NAS. 10 patients (4 %) had musculoskeletal disease (arthrosis, spinal stenosis or trauma) and 38 patients (13 %) no diagnoses.

Sex distribution was equal between groups, apart from some smallest groups. At the first consultation AD and AD+VAD patients were older than NPH and FTLD patients (AD/NPH p=0.006, AD/FTLD p=0.006, AD+VAD/NPH p=0.036, AD+VAD/FTLD p=0.007, post-hoc LSD), DLB patients were older in comparison with FTLD patients (p=0.011, post- hoc LSD), AD patients were older compared to patients with other neurologic disease (p=0.038, post-hoc LSD) and non-diagnosed patients were older in comparison with FTLD patients (p=0.038, post-hoc LSD).

Considering the appearance of memory deficiency and gait impairment, there were clear differences between groups (p=0.003, p=0.011, respectively, Kendall’s tau-b).

Over half of AD patients (60 %) suffered from cognitive symptoms on admission. About half of patients later developing VAD, VAD+AD and FTLD (54, 44 and 50 %, respectively) had memory deficiency in the baseline, while almost half of patients having other

neurologic diagnoses or no diagnosis at the end of follow-up (41 and 40 %, respectively) presented with prior cognitive problems. Only one third (33 %) of DLB patients and one out of four (27 %) of NPH patients had memory problems on admission. Baseline

cognitive issues were the least common in patients with musculoskeletal diseases (10 %) or PD (0 %) .

On the contrary, almost all patients with PD or musculoskeletal diseases (both 80 %) suffered from gait impairment on admission. Walking difficulty dominated in baseline symptomatology also in patients having NPH, FTLD or no diagnosis (69, 67 and 71 %, respectively). Over half of VAD patients (56 %) priorly suffered from gait impairment, while less than half of AD and AD+VAD patients (43 and 39 %, respectively) manifested with walking difficulties in baseline. Gait impairment on admission was the least

common in patients developing DLB (33 %).

Considering the appearance of parkinsonian symptoms, there were no statistically significant differences between the groups (p=0.118, Kendall’s tau-b). Prevalence of tremor or rigidity on admission was the highest in PD patients (two patients, 40 %), followed by patients developing DLB (1 patient, 17 %), FTLD (1 patient, 17 %) and no diagnosis (4 patients, 15 %). There were a few cases also in other diagnosis groups (prevalence less than 10 %) presenting parkinsonian symptoms in the baseline. Tremor or rigidity was present on admission in 6 NPH patients (5 %).

Tap test response distribution differed between groups (p=0,024, Kendall’s tau-b).

Responses were mostly positive in NPH and FTLD groups (74 and 83 %, respectively).

There were equally positive and negative results in AD, AD+VAD and DLB. Less than half of patients with VAD, other neurologic diagnosis and musculoskeletal diseases (33, 48, 40 %, correspondingly) responded. Responses were mostly negative in patients having PD (only one case, 20,0 %, with responding) or no diagnosis (19 % positive results).

CSF Abeta1-42 mean distribution was equal between groups (p=0.210, ANOVA).

Concentrations were the lowest among patients with DLB (620 ± 161 pg/ml), in contrast with PD patients having the highest levels (943 ± 354 pg/ml). In general, also AD, AD+VAD and non-diagnosed patients had lower (731 ± 245 ± 169 and 715 ± 235 pg/ml,

respectively) and musculoskeletal disease patients higher (812 ± 285 pg/ml) Abeta1-42 mean than the others. NPH patients were in the middle having Abeta1-42 concentration of 790 ± 214 pg/ml.

On the contrary, p-tau and t-tau values differed significantly between groups (p<0.001,

p=0.006, respectively, Kruskall-Wallis). Their means were exceptionally high for VAD patients (p-tau 57 ± 69 and t-tau 306 ± 341 pg/ml), closely followed by AD, AD+VAD and DLB patients (for all groups p-tau ≥ 40 and t-tau ≥ 250 pg/ml). p-tau and tau means were in the middle range for groups of PD, other neurologic diagnoses, musculoskeletal disease and patients with no diagnosis. The lowest levels were measured from NPH and FTLD patients (p-tau 33

± 11 and 30 ± 12 pg/ml, t-tau 182 ± 78 and 193 ± 94 pg/ml, correspondingly).

There were no differences on aSyn means between the diagnostic groups (p=0.966, ANOVA). The two PD patients having aSyn measured had particularly high (mean 1579 ± 406 pg/ml) and the two DLB and the two FTLD patients having the results had especially low aSyn levels (means 920 ± 175 and 977 ± 406 pg/ml, respectively).

MMSE scores differed significantly between groups both in baseline (p=0.014, ANOVA) and end-point (p<0.001, Kruskall-Wallis). Baseline MMSE mean was lower in AD than NPH patients (p<0.001, post-hoc LSD) and in patients with other neurologic diagnosis compared to NPH and musculoskeletal disease patients (p=0.002 and p=0.030, post-hoc LSD). At the end of follow-up MMSE scores had remained the highest in NPH, PD and musculoskeletal disease groups (23,1 ± 4,3, 25,0 ± 5,3 and 24,3 ± 2,6, respectively) and declined below 20 in AD, VAD, AD+VAD, DLB and other neurologic diagnose groups.

Prevalence of end-point MCI and dementia differed significantly between groups (both p<0.001, Kendall’s tau-b). Naturally, almost all patients with AD, AD+AD, VAD, FTLD and DLB had dementia at the end of follow-up. Almost half of NPH patients developed MCI or dementia (35 and 9 %, respectively), while only one of the five PD patients (20 %) had cognitive decline and progressed to dementia during the follow-up. MCI or dementia was present also in other groups (more than half of the patients with neurologic diagnoses or no diagnosis, less than half of musculoskeletal diseases patients).

Considering distribution of shunt treatment and response, there were differences between diagnostic groups (p<0.001, Kendall’s tau-b). As expected, shunting was the most common for patients confirmed as having NPH (98 % of the group having shunt treatment, forming 58 % of all shunted patients), with a success rate of 81 % (forming 60

% of all shunt-responders). About half of the patients developing AD or VAD were priorly shunted (57 and 44 %, respectively), and vice versa, from priorly shunted patients 16 % developed AD and or 4 % VAD. As much as 71 % of AD and 43 % of VAD patients

responded in the first place (forming 14 and 2 % of all shunt-responders,

correspondingly). Exceptionally, 83 % of DLB and FTLD patients had undergone shunt surgery while more than half of them (80 and 60 %, respectively) had benefited from the treatment. Moreover, 3 of 5 patients having PD at the end of follow-up were shunted in the baseline, all of them with response. Shunting and beneficence was frequent also in

other neurological diagnoses (70 % shunted, 67 % responded) and musculoskeletal diseases (40 % shunted, 100 % responded).